Patients requiring treatment with a RANKL inhibitor (e.g. denosumab) who cannot discontinue it before treatment with atezolizumabXx_NEWLINE_xXPrior treatment with a MEK inhibitor or ERK inhibitorXx_NEWLINE_xXPrior systemic therapy with a MEK inhibitorXx_NEWLINE_xXReceived a prior IDH inhibitor.Xx_NEWLINE_xXPrior treatment with any RAF inhibitor, MEK inhibitor, cetuximab, panitumumab or other EGFR inhibitorsXx_NEWLINE_xXReceived JAK inhibitor therapy after allo-HSCT for any indication. Treatment with a JAK inhibitor before allo-HSCT is permitted.Xx_NEWLINE_xXIrinotecan, temozolomide and mammalian target of rapamycin (mTOR) inhibitor exposure:\r\n* Patients who have received prior single agent therapy with irinotecan, temozolomide, or an mTOR inhibitor, excluding ABI-009, are eligible\r\n* Patients who have received prior therapy with ABI-009 are not eligible\r\n* Patients who have previously received irinotecan and temozolomide in combination without progressive disease while on therapy are eligible\r\n* Patients who have previously received irinotecan and temozolomide in combination and had significant toxicity with these two drugs are not eligible\r\n* Patients who have received prior therapy with all three agents in combination (i.e. irinotecan, temozolomide, and an mTOR inhibitor) are not eligibleXx_NEWLINE_xXThe patient has received prior therapy with bevacizumab, ramucirumab or any PARP inhibitor, including olaparibXx_NEWLINE_xXPrior treatment with any VEGF inhibitorXx_NEWLINE_xXDocumented history of prior tamoxifen, aromatase inhibitor, or raloxifene in last 6 monthsXx_NEWLINE_xXPrior receipt of a selective FGFR inhibitor.Xx_NEWLINE_xXNo prior treatment with crizotinib or another ALK inhibitorXx_NEWLINE_xXPatients must not have received a prior BRAF or mitogen-activated protein kinase kinase (MEK) inhibitorXx_NEWLINE_xXPatients must NOT be receiving valproic acid, an histone deacetylase (HDAC) inhibitor, and may not have previously received any HDAC inhibitor prior to enrollment (e.g. valproic acid, entinostat, vorinostat) unless discussed with the study chair; patients must not have received prior HDAC therapy for the treatment of their malignancyXx_NEWLINE_xXNo prior anti-MET therapy such as crizotinib or cabozantinib, or PD-1/PD-L1 immune checkpoint inhibitor therapy (such as nivolumab, pembrolizumab, atezolizumab) or CTLA4 inhibitor therapy (such as ipilimumab); no prior allergic reaction to small molecule tyrosine kinase inhibitors or monoclonal antibodies\r\n* Exception for targeted therapy sub-study (Arm T): Prior crizotinib may be allowed depending on the gene alterationXx_NEWLINE_xXPatients who have had hormonal therapy (e.g., tamoxifen, aromatase inhibitor) within 1 week prior to entering the studyXx_NEWLINE_xXRefractory disease to treatment with an mTOR inhibitorXx_NEWLINE_xXPatient is INELIGIBLE if patient discontinued prior mTOR inhibitor due to toxicityXx_NEWLINE_xXPatient must NOT have had previous treatment with any PI3K or AKT inhibitorXx_NEWLINE_xXNo prior proteasome inhibitor or immune-modulating drug (IMiD) useXx_NEWLINE_xXPatients who have previously received temsirolimus, another mTOR inhibitor, or any other investigational agentXx_NEWLINE_xXProteasome inhibitor naive or sensitive disease; proteasome inhibitor sensitive disease is defined as a PR or better to prior proteasome inhibitor-based therapy that is maintained for >= 60 days from the last dose of the proteasome inhibitor\r\n* A patient who receives induction therapy with lenalidomide, bortezomib and dexamethasone and achieves a PR or better but subsequently progresses on continued lenalidomide or lenalidomide-dexamethasone would be eligible provided the progression occurs 60 days or more after discontinuation of the bortezomib; similarly, ixazomib exposure is allowed provided they meet the definition of proteasome inhibitor sensitive diseaseXx_NEWLINE_xXPrior treatment with dasatinib, or any BCR-ABL1 inhibitor other than imatinibXx_NEWLINE_xXPatients must not require treatment with a RANKL inhibitor (e.g. denosumab) who cannot discontinue it before treatment with atezolizumabXx_NEWLINE_xXThe use of hormonal therapy is not allowed; if the patient in on a 5-alpha reductase inhibitor, then they should be stopped prior to treatment once enrolled onto the study; no washout period is required for this study to participateXx_NEWLINE_xXNot previously received XL184 or another MET/HGF inhibitor (tivantinib or crizotinib); there are no limits on number of prior therapeutic regimens; patients who have been treated with prior VEGF pathway, or RET inhibitors (except XL184) may be eligibleXx_NEWLINE_xXPrevious treatment with XL184 (cabozantinib) or another MET/HGF inhibitor (tivantinib, crizotinib)Xx_NEWLINE_xXPatients who have received prior therapy with a specific inhibitor of TRK (including but not limited to entrectinib [RXDX-101], DS-6051b, and PLX7486) are not eligibleXx_NEWLINE_xXPrior therapy with any CDK inhibitor.Xx_NEWLINE_xXPatients requiring treatment with a RANKL inhibitor (e.g. denosumab) who cannot discontinue it before treatment with atezolizumabXx_NEWLINE_xXUse of orlistat or any other known FASN inhibitor within 6 months prior to study entryXx_NEWLINE_xXPrior therapy with PLX3397 unless discontinued for intolerance (i.e., non-progression on prior kinase inhibitor)Xx_NEWLINE_xXTumors with driver mutations (epidermal growth factor receptor mutation positive or anaplastic lymphoma kinase fusion oncogene positive) treated with a tyrosine kinase inhibitor or crizotinib are eligible. For participants who have progressed on a tyrosine kinase inhibitor or crizotinib or are intolerant to this targeted therapy, that participant must receive platinum-based therapy prior to enrollment in this study. Documentation of such mutations must be available and entered into the electronic case report form (eCRF).Xx_NEWLINE_xXGroup 2: Melanoma: All patients must have been tested for BRAF mutations. Patients with V600 mutation positive melanoma must have clinical or radiological evidence of disease progression during or after treatment with a BRAF inhibitor alone or in combination with other agents.Xx_NEWLINE_xXPrior treatment with a phosphatidylinositol 3 (PI3)-kinase, v-akt murine thymoma viral oncogene homolog 1 (AKT) or mammalian target of rapamycin (mTOR) inhibitor in which the patient experienced a grade >= 3 drug-related adverse event or otherwise would be at increased risk for additional PI3K-related toxicityXx_NEWLINE_xXPrior treatment with a smoothened inhibitor (SMOi) and/or hypomethylating agent.Xx_NEWLINE_xXPatients who have received >= 7 days of prior ibrutinib or any prior treatment with another Bruton tyrosine kinase (BTK) inhibitor are not eligibleXx_NEWLINE_xXPatients who have previously been treated with an IL-6, JAK or STAT inhibitor for any indication, such as ruxolitinib or tocilizumabXx_NEWLINE_xXPatients known to have Philadelphia chromosome positive (Ph+) ALL must have either failed treatment or been intolerant to treatment with at least one second or third generation tyrosine kinase inhibitorXx_NEWLINE_xXReceipt of >1 line of therapy that includes a second generation androgen inhibitor for treatment of mCRPCXx_NEWLINE_xXPatients with BRAF-positive tumor(s) are eligible for the study if they received prior treatment with a BRAF inhibitor (alone of in combination with a MEK inhibitor) or declined targeted therapy.Xx_NEWLINE_xXProgressing following PD-1 based checkpoint inhibitor therapy, with or without ipilimumab; tumors harboring BRAF V600 alterations must also have received prior therapy with BRAF inhibitors (with or without a MEK inhibitor) (for treatment phase)Xx_NEWLINE_xXReceived prior tyrosine kinase inhibitor therapy or palliative radiation within 7 days of first dose of study treatment.Xx_NEWLINE_xXReceived prior treatment with a phosphoinositide-3-kinase (PI3K) inhibitorXx_NEWLINE_xXAny previous treatment with a PARP inhibitor, including olaparibXx_NEWLINE_xXPrevious treatment with venetoclax or other B-Cell Lymphoma 2 (BCL-2) inhibitor OR previous treatment with daratumumab or other anti-CD38 therapy.Xx_NEWLINE_xXParticipant is refractory to any proteasome inhibitor, defined as progression on or within 60 days of the last dose of a proteasome inhibitor-containing regimen.Xx_NEWLINE_xXParticipant has had prior treatment with proteasome inhibitor within 60 days prior to first dose of study drug.Xx_NEWLINE_xXExpansion Cohort B (Ribociclib + PDR001 + Fulvestrant): Prior hormonal therapy:\r\n* Participants may have received any number of previous endocrine / hormonal lines of therapy in the metastatic setting, as long as the last dose is >= 14 days prior to first dose of study treatment\r\n* Participants must have progressed on an aromatase inhibitor in the metastatic setting or experienced disease recurrence within 6 months of completing adjuvant therapy with an aromatase inhibitor\r\n* Treatment with prior fulvestrant is prohibitedXx_NEWLINE_xXMust have relapsed and/or refractory MM, having received treatment with proteasome inhibitor and IMiDXx_NEWLINE_xXRenal cell patients must have had at least one prior VEGF tyrosine kinase inhibitor (TKI)Xx_NEWLINE_xXPatients with melanoma should have unresectable or metastatic disease; melanoma patients with BRAF V600E or V600K mutation-positive melanoma who have previously received a BRAF inhibitor with or without a MEK inhibitor) are eligibleXx_NEWLINE_xXAny previous treatment with pevonedistat or other NEDD8 inhibitorXx_NEWLINE_xXParticipants with known anaplastic lymphoma kinase (ALK) translocations which are sensitive to available targeted inhibitor therapy are excludedXx_NEWLINE_xXPrior treatment with a mitogen activated-protein kinase (MAPK) inhibitorXx_NEWLINE_xXProteasome inhibitor therapy (e.g. bortezomib or carfilzomib) -2 weeksXx_NEWLINE_xXPrior treatment with idelalisib, other selective PI3K? inhibitors, or a pan-PI3K inhibitor.Xx_NEWLINE_xXPrior treatment with a Bruton's tyrosine kinase inhibitor (eg, ibrutinib).Xx_NEWLINE_xXHistory of prior significant toxicity (Grade 2 or higher that required permanent treatment discontinuation) from a BRAF, MEK (MAPK [Mitogen-activated protein]/ERK kinase) or ERK inhibitor.Xx_NEWLINE_xXPrior treatment with CDK4/6 inhibitorXx_NEWLINE_xXParticipants who have received previous treatment with a mammalian target of rapamycin (mTOR) inhibitorXx_NEWLINE_xXSubject who has been previously treated with an anti-CCR4 antibody or an IDO1 inhibitor;Xx_NEWLINE_xXPatients requiring treatment with a RANKL inhibitor (e.g. denosumab) who cannot discontinue it before treatment with atezolizumabXx_NEWLINE_xXPrior treatment with any PARP inhibitorXx_NEWLINE_xXPrior treatment (at least 1 full treatment cycle) with a farnesyltransferase inhibitor.Xx_NEWLINE_xXPrior treatment with a MEK, Ras or Raf inhibitorXx_NEWLINE_xXPrior exposure to a bromodomain inhibitor, such as OTX-015 or CPI-0610.Xx_NEWLINE_xXPrior exposure to a WNT inhibitorXx_NEWLINE_xXParticipants who have previously received a cyclin-dependent kinase (CDK) 4/6 inhibitorXx_NEWLINE_xXFor Phase 2 - Prior exposure to a receptor tyrosine kinase or mammalian target of Rapamycin inhibitorXx_NEWLINE_xXPrevious therapy with histone deacetylase (HDAC) inhibitor.Xx_NEWLINE_xXPrevious treatment with any prior BET inhibitor therapyXx_NEWLINE_xXPatients who have received prior treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus)Xx_NEWLINE_xXPatient who received any CDK4/6 inhibitorXx_NEWLINE_xXPrior treatment with a CDK 4/6 inhibitor.Xx_NEWLINE_xXPrior therapy with AT13387 or another HSP90 inhibitorXx_NEWLINE_xXCrizotinib, or any other cMET inhibitor or HGF-targeting inhibitor.Xx_NEWLINE_xXHas documented disease progression while receiving at least 30 days of treatment with a currently approved EGFR tyrosine kinase inhibitor (TKI) (e.g., erlotinib, gefitinib or afatinib) with intervening treatment after most recent EGFR TKI therapy (not required for \de novo\ T790M EGFR mutation).Xx_NEWLINE_xXRefractory to prior checkpoint inhibitor therapy (received less than 6 months of treatment)Xx_NEWLINE_xXPrevious treatment with a selective FGF19-FGFR4 targeted therapy and/or pan-FGFR inhibitor.Xx_NEWLINE_xXPrior treatment with or intolerance to proteasome inhibitor and immunomodulatorXx_NEWLINE_xXThe subject has received cabozantinib or another c-Met inhibitor (please note ARQ 197 is not considered a MET inhibitor for purposes of this study)Xx_NEWLINE_xXMust have received at least one course of therapy with a VEGFR-targeting tyrosine kinase inhibitor (eg, sorafenib, sunitinib, axitinib, pazopanib or tivozanib) and progressed within 6 months of planned first dose of study treatmentXx_NEWLINE_xXPrior treatment with everolimus, or any other specific or selective TORC1/PI3K/AKT inhibitor (eg, temsirolimus)Xx_NEWLINE_xXReceipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before planned first dose of study drugXx_NEWLINE_xXFor Part G (abemaciclib + LY3023414 + fulvestrant): The participant may have received prior systemic endocrine therapy with at least one nonsteroidal aromatase inhibitor (anastrozole, letrozole) for metastatic disease.Xx_NEWLINE_xXFor Parts A, B, C, D, E, F, H: Have received prior therapy with a CDK4/6 inhibitor, Part G: Have received prior therapy with fulvestrant or any PI3K and/or mTOR inhibitor (including LY3023414); Part I: Have received prior treatment with abemaciclib in any setting.Xx_NEWLINE_xXPrior therapy is allowed; for patients enrolled in the Phase II portion of the study, patients may have received prior immunotherapy (including high-dose IL-2, ipilimumab, nivolumab, and other anti-PD1/PDL1 antibodies) or chemotherapy; however prior navitoclax, BRAF inhibitor and/or MEK inhibitor therapy will not be allowedXx_NEWLINE_xXPrior navitoclax, BRAF inhibitor, and MEK inhibitor is prohibited; (exceptions for Phase I are described above)Xx_NEWLINE_xXPrior treatment with an MDM2 inhibitor.Xx_NEWLINE_xXPrior therapy with any cyclin-dependent kinase (Cdk) 4 inhibitorXx_NEWLINE_xXPrevious treatment with sunitinib or kinase inhibitor other than imatinib Wash-outXx_NEWLINE_xXSubjects known to be refractory to any proteasome inhibitor other than bortezomib or carfilzomib, including but not limited to MLN9708, CEP-18770, ONX 0912, and SalmosporamideA; refractory will be defined as a history of progression on or within 60 days after completing a regimen containing the proteasome inhibitor for a minimum of 2 cycles at either approved or considered effective or best tolerated dosesXx_NEWLINE_xXPrior EGFR tyrosine kinase inhibitor therapy (including gefitinib, erlotinib, or any experimental EGFR tyrosine kinase inhibitor [TKI] agent)Xx_NEWLINE_xXConcomitant treatment with strong inhibitor of P-glycoprotein (P-gp)Xx_NEWLINE_xXPatients who have received prior treatment with an mTOR inhibitorXx_NEWLINE_xXThe subject has a histologic or cytologic diagnosis of colorectal adenocarcinoma that is metastatic or unresectable and is refractory to or progressed (or relapsed) following a fluoropyrimidine, irinotecan, oxaliplatin, and bevacizumab; prior epidermal growth factor inhibitor therapy is required for patients with left-sided, RAS wild-type tumors; prior Food and Drug Administration (FDA)-approved PD-1 inhibitor therapy is required for patients with microsatellite instability high (MSI-H) colorectal cancer. Prior regorafenib or TAS-102 treatment is not requiredXx_NEWLINE_xXReceipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 14 days before the first dose of study treatment. Note: Subjects with prostate cancer currently receiving luteinizing hormone releasing hormone (LHRH) or gonadotropin-releasing hormone (GnRH) agonists may be maintained on these agentsXx_NEWLINE_xXSubjects treated, or anticipated to be treated, with a calcineurin inhibitor (because concomitant use of sirolimus and a calcineurin inhibitor increases the risk of calcineurin inhibitor-induced hemolytic uremic syndrome/thrombotic thrombocytopenic purpura/thrombotic microangiopathy [HUS/TTP/TMA]).Xx_NEWLINE_xXPatients should be excluded if they have had prior treatment with the combination of a PI3K inhibitor and a PD-1 inhibitorXx_NEWLINE_xXFor enrollment to the phase II portion: participants who have not received prior BRAF or MEK inhibitor therapyXx_NEWLINE_xXRequire continued treatment with a medication that is known to be a strong inhibitor of CYP2C8.Xx_NEWLINE_xXTreatment with gemfibrozil (strong CYP2C8 inhibitor) within 14 days before the first dose of TAK-580Xx_NEWLINE_xXPatients can have received any number of prior therapies for treatment of their uveal melanoma excluding prior treatment with an ERK inhibitor; patients who have received prior MEK inhibition or other MAPK targeted agents will be allowed on studyXx_NEWLINE_xXPrior treatment with a PARP inhibitorXx_NEWLINE_xXPatients must not have other therapeutic options known to provide clinical benefit in MM available to them. Prior lines of therapy must include at least a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody.Xx_NEWLINE_xXHas been previously treated with an Indoleamine-2,3-dioxygenase-1 (IDO1) inhibitor (e.g., epacadostat, BMS-986205)Xx_NEWLINE_xXPrior treatment with any immune checkpoint inhibitor and/or an IDO inhibitor.Xx_NEWLINE_xXPrior treatment with a known PARP inhibitorXx_NEWLINE_xXPatients requiring treatment with a RANKL inhibitor (e.g. denosumab) who cannot discontinue it before treatment with atezolizumabXx_NEWLINE_xXResistance or intolerance to prior kinase inhibitor therapy (e.g., lenvatinib, sorafenib). A patient who is considered inappropriate for, or who has refused, kinase inhibitor therapy may be enrolled with approval of the Medical Monitor.Xx_NEWLINE_xXParticipants who have received prior treatment with a CDK4/6 inhibitorXx_NEWLINE_xXAllowable prior therapies:\r\n* Subjects must have had clinical or radiographic progression on imatinib; those who were taken off of imatinib for intolerance must have progressed on at least one other tyrosine kinase inhibitor (TKI)\r\n* Subjects must have received >= 1 prior systemic therapy (including imatinib); a maximum of 4 prior therapies for metastatic disease are allowedXx_NEWLINE_xXConcurrent use of any medication that is an inhibitor of UGT1A9 during the screening or treatment periodXx_NEWLINE_xXPrior treatment with cobimetinib or a MEK inhibitorXx_NEWLINE_xXPrior therapy with any known inhibitor of MNK-1 or MNK-2.Xx_NEWLINE_xXPrior treatment with small molecule bromodomain and extra terminal (BET) family inhibitor.Xx_NEWLINE_xXone prior hormonal therapy and a Cyclin-dependent kinase (CDK)4/6 inhibitor. Note: Participants may have received treatment for brain metastases, but must be neurologically stable, completed radiotherapy and off corticosteroids for at least one month prior to starting trial therapy.Xx_NEWLINE_xXIs either refractory to or intolerant of at least one proteasome inhibitor and a least one immunomodulatory drug. In addition, after the MTD/OBD is defined, must also be either refractory to of at least one anti-CD38 monoclonal antibody.Xx_NEWLINE_xXSubjects who were intolerant to a BTK inhibitorXx_NEWLINE_xXPatients must have progressed on prior approved checkpoint inhibitor therapy, not tolerated approved checkpoint inhibitor therapy, or have a contraindication to approved checkpoint inhibitors; patients with stable disease after approved checkpoint inhibitor therapy will also be eligibleXx_NEWLINE_xXPatients whose melanomas harbor a BRAF V600E or V600K mutation must have progressed on a RAF inhibitor; patients who had to discontinue RAF inhibitor therapy because of toxicity but who did not progress will be eligible unless they responded to therapy; in that case, they will not be eligible unless they progressXx_NEWLINE_xXPart 2, Cohort 1, Patients must have received ? 3 prior treatment regimens for ovarian cancer including a platinum-based regimen. Patients whose OC harbors a mutation in breast cancer gene (BRCA), either germline or somatic, must have been previously treated with a poly(ADP ribose) polymerase (PARP) inhibitor, or be considered unwilling or ineligible for treatment with a PARP inhibitorXx_NEWLINE_xXFor enrollment to the phase II portion: participants must have a histologically confirmed melanoma with a BRAF V600E or BRAF V600K mutation (identified via NextGen sequencing using the DFCI/BWH OncoPanel or any CLIA-certified method) and cannot have received prior BRAF or MEK inhibitor therapyXx_NEWLINE_xXFor enrollment to the phase I portion: there is no required washout period for BRAF or MEK inhibitor therapyXx_NEWLINE_xXFor enrollment to the phase II portion: participants who have received prior BRAF or MEK inhibitor therapyXx_NEWLINE_xXPrior treatment with a PARP inhibitorXx_NEWLINE_xXPrevious treatment with a CDK 4/6 inhibitor or an mTOR inhibitorXx_NEWLINE_xXPatients who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study; patients who have received prior PARP inhibitor will not be excluded; patients who have received prior CHK1 inhibitor will be excludedXx_NEWLINE_xXThe melanoma must harbor an activating BRAF V600 mutation; prior therapy with a BRAF and/or MEK inhibitor is allowed in the dose-escalation phase only; however, patients who discontinued previous RAF inhibitor due to intolerance of the drug rather than due to progression will not be eligibleXx_NEWLINE_xXIn the dose expansion phase of the trial, prior treatment with a BRAF inhibitor will be an exclusion criterionXx_NEWLINE_xXParticipants who have received a prior inhibitor of Wee1 kinase activityXx_NEWLINE_xXPrior therapy with any CDK inhibitorXx_NEWLINE_xXPhase II: Subjects who have progressed on first-line systemic therapy (either platinum-based chemotherapy with or without immune checkpoint inhibitor or immune checkpoint inhibitor as first line therapy) who are candidates for second-line systemic therapy.Xx_NEWLINE_xXPhase II: Subjects with an EGFR or ALK mutation who are no longer candidates for TKI therapy and have progressed on standard systemic therapy (either platinum-based chemotherapy with or without immune checkpoint inhibitor or immune checkpoint inhibitor as first line therapy).Xx_NEWLINE_xXPrevious treatment with erlotinib or any other EGFR inhibitorXx_NEWLINE_xXPrevious treatment with vemurafenib or any other BRAF inhibitor (prior sorafenib is allowed)Xx_NEWLINE_xXPrevious treatment with cobimetinib or any other mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitorXx_NEWLINE_xXPrior treatment with a RAF inhibitorXx_NEWLINE_xXPrevious treatment with vismodegib or any other hedgehog pathway inhibitorXx_NEWLINE_xXPrevious treatment with alectinib or any other ALK inhibitorXx_NEWLINE_xXPatients who have been previously treated with an mTOR inhibitorXx_NEWLINE_xXPrior treatment with CYP17 inhibitor (e.g. ketoconazole, abiraterone acetate, galeterone) or second generation androgen receptor antagonist including apalutamide or enzalutamideXx_NEWLINE_xXUse of 5-alpha reductase inhibitor within 42 days prior to randomizationXx_NEWLINE_xXPrevious BRAF inhibitor use such as vemurafenib, GSK2118436 or sorafenibXx_NEWLINE_xXPrior treatment with WEE1 inhibitorXx_NEWLINE_xXPrior treatment with Mcl-1 inhibitor.Xx_NEWLINE_xXChemotherapy, monoclonal antibody, or small molecule kinase inhibitor =< 21 days prior to first administration of study treatmentXx_NEWLINE_xXPrior exposure to a BTK or BCL-2 inhibitorXx_NEWLINE_xXPrior treatment with a drug of the focal adhesion kinase (FAK) inhibitor class.Xx_NEWLINE_xXParticipants enrolling to the MET cohort who have received treatment with a prior MET inhibitor must be able and willing to undergo a baseline tumor biopsyXx_NEWLINE_xXParticipant is currently taking a strong CYP2C8 inhibitor (e.g. gemfibrozil [Lopid])Xx_NEWLINE_xXParticipants who have received prior treatment with a CHK1 inhibitor.Xx_NEWLINE_xXHave previously completed or withdrawn from this study or any other study investigating an ERK1/2 inhibitor.Xx_NEWLINE_xXPrior treatment (at least 1 full treatment cycle) with a farnesyltransferase inhibitor.Xx_NEWLINE_xXPrior treatment with any investigational proteasome inhibitor within 6 months of study entryXx_NEWLINE_xXPrior systemic anti-cancer therapy of any kind for RCC, including but not limited to any approved agent or any previous treatment with a PD1 or PD-L1 inhibitor including durvalumab; no previous treatment with immunotherapy for any malignancy including cytokine, anti-tumor vaccine, T-cell activator, co-stimulator or immune checkpoint inhibitorXx_NEWLINE_xXPrevious anti-cancer and investigational agents within 2 weeks before first dose of INC280; if previous treatment is a small molecule tyrosine kinase inhibitor (TKI), last dose must be at least 7 days before first dose of INC280; a shorter washout period may be allowed after discussion with the principal investigatorXx_NEWLINE_xXSubjects must have received 1 or more prior systemic therapies for this disease, (this can include neo-adjuvant or adjuvant chemotherapy if administered < 2 years prior to study enrollment), should not have had prior treatment with immunotherapy; (including immune checkpoint inhibitor drugs, or immunotherapy vaccines); patients with epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) alterations will need to have progressed on a tyrosine kinase inhibitor (TKI) treatmentXx_NEWLINE_xXPrior treatment with PI3K-inhibitorXx_NEWLINE_xXPrior treatment with Bromodomain and Extra-Terminal (BET) inhibitorXx_NEWLINE_xXPrior treatment with selumetinib or another specific MEK 1/2 inhibitorXx_NEWLINE_xXEGFR-mutation positive patients must have progressed on or had intolerance to an EGFR small molecule tyrosine kinase inhibitorXx_NEWLINE_xXPatients whose tumors harbor an anaplastic lymphoma kinase (ALK) translocation must have progressed on or had intolerance to an ALK inhibitor;Xx_NEWLINE_xXPrior treatment on a CDK inhibitorXx_NEWLINE_xXA history of prior treatment with IL-2, ipilimumab or prior cytotoxic T-lymphocyte antigen 4 (CTLA4) inhibitor or agonistXx_NEWLINE_xXPatients must have been previously treated with an immunomodulatory drug (IMiD) and proteasome inhibitor, must be refractory to carfilzomib defined as progression on or within 2 months of a carfilzomib-containing therapy, and must be progressingXx_NEWLINE_xXPrior treatment with bevacizumab or other direct VEGF/ VEGFR inhibitors. For any question of the definition of a direct VEGF/VEGFR inhibitor, consult Sponsor.Xx_NEWLINE_xXPatients previously treated with a Janus kinase (JAK) inhibitorXx_NEWLINE_xXParts B3, B4, B5 & B6: No previous treatment with any PI3K and/or mTOR inhibitorXx_NEWLINE_xXIntolerance to any previous treatment with any phosphatidylinositol-3-kinase (PI3K) and/or mammalian target of rapamycin (mTOR) inhibitor.Xx_NEWLINE_xXThe patients BRAF mutation status at position 600 must be known prior to enrollment; patients with V600E mutations are eligible if they have failed an approved BRAF inhibitor or MEK inhibitor therapy or have been offered an approved BRAF inhibitor or MEK inhibitor therapy and refusedXx_NEWLINE_xXPatients whose BRAF V600E mutation status is unknown, have the BRAF V600E mutation and are responding to a BRAF inhibitor or MEK inhibitor therapy, or have the BRAF V600E mutation and have not been offered the option of receiving a BRAF inhibitor or MEK inhibitor therapy for the treatment of their melanomaXx_NEWLINE_xXPrevious therapy with histone deacetylase (HDAC) inhibitorXx_NEWLINE_xXPatients previously treated with a poly adenosine diphosphate (ADP) ribose polymerase (PARP) inhibitor may be enrolled provided:\r\n* PARP inhibitor was not the most recent treatment\r\n* PARP inhibitor treatment was discontinued > 6 months before the first planned dose of rucaparibXx_NEWLINE_xXPrior therapy with a cyclin-dependent kinase (CDK) inhibitorXx_NEWLINE_xXTreatment-naive and previously treated patients will be included; however, patients may not have received a BRAF or MEK inhibitor in the past 24 weeksXx_NEWLINE_xXSubjects previously treated with BRAF/MEK inhibitor therapy in the past 24 weeksXx_NEWLINE_xXPatients who have received any previous treatment with a PARP inhibitor, including olaparibXx_NEWLINE_xXPrior treatment with CTLA-4 inhibitorXx_NEWLINE_xXIf BRAFV600-mutant, refractory disease to at least one BRAF inhibitor and a MEK inhibitor (defined as progression while on treatment), or intolerance to these drugsXx_NEWLINE_xXPhiladelphia chromosome positive (Ph+) patients must be refractory to or intolerant of standard tyrosine kinase inhibitor therapyXx_NEWLINE_xXGVHD prophylaxis must include a calcineurin inhibitor combined with methotrexate or mycophenolate.Xx_NEWLINE_xXThe patient has taken a medication known to be a potent inhibitor of CYP1A2, CYP2C8, or CYP3A4 within 2 weeks prior to the first dose of study drugXx_NEWLINE_xXPrior treatment with a PARP inhibitor, including olaparib.Xx_NEWLINE_xXHistory of exposure to alvocidib or any other cyclin-dependent kinase 9 (CDK9) inhibitor.Xx_NEWLINE_xXPrior therapy with EGFR tyrosine kinase inhibitor (TKI) therapyXx_NEWLINE_xXPrevious exposure to a CDK4/6 inhibitor (palbociclib, abemaciclib, or ribociclib)Xx_NEWLINE_xXSTRATUM B: Previous exposure to a MEK inhibitor (i.e., trametinib, selumetinib)Xx_NEWLINE_xXSTRATUM C: Participants previously treated with a smoothened inhibitor must have received their last dose > 6 months prior to study enrollmentXx_NEWLINE_xXPrior exposure to T cell checkpoint inhibitor therapies.Xx_NEWLINE_xXHypersensitivity to any JAK inhibitorXx_NEWLINE_xXSubjects who require therapy with a strong CYP3A4 inhibitor prior to enrollment to this studyXx_NEWLINE_xXKnown intolerance to or life threatening side effects resulting from prior checkpoint inhibitor therapyXx_NEWLINE_xXPrior treatment with JAK2 inhibitor therapy is not excluded. Patients on a JAK2 inhibitor may continue through conditioning until day -3 then tapered at the discretion of the investigator.Xx_NEWLINE_xXPresence of measurable AML that has progressed during or relapsed after prior therapy, including ?1 regimen containing a FLT3 kinase inhibitor.Xx_NEWLINE_xXRequires treatment with a strong cytochrome P(CYP)450 3A inhibitor OR subjects who have received a strong cytochrome P(CYP)450 3A inhibitor within 7 days prior to the first dose of ibrutinib or subjects who require continuous treatment with a strong CYP 450 3A inhibitorXx_NEWLINE_xXCurrently treated with hormone therapy-based regimen, including selective estrogen receptor modulators (SERMs), aromatase inhibitors, selective estrogen receptor down regulators (SERDs), CYP17A1 inhibitors, gonadotrophin releasing hormone (GnRH) agonists/antagonists, and antiandrogens; concurrent anti-HER2 therapy and other targeted therapy (e.g., CDK4/6 inhibitor, mTOR inhibitor) is permitted; must have started the current regimen at least 4 weeks prior to enrollmentXx_NEWLINE_xXPrior treatment with any PD-1 or PDL-1 inhibitorXx_NEWLINE_xXNo history of prior BTK-inhibitor-containing therapy.Xx_NEWLINE_xXPrevious treatment with and disease progression on a combination of a VEGF inhibitor and an immune checkpoint inhibitor. Patients who have been treated with and have progressed on a single agent VEGF inhibitor OR an immune checkpoint inhibitor will not be excludedXx_NEWLINE_xXPatients who have previously received an immune checkpoint inhibitor (e.g., anti- PD-L1, anti-PD-1, anti-CTLA-4) prior to enrollment must have toxicities related to the checkpoint inhibitor resolved to ? Grade 1 or baseline (prior to the checkpoint inhibitor) to be eligible for enrollment. Patients who experienced previous hypothyroidism toxicity on a checkpoint inhibitor are eligible to enter study regardless of Grade resolution as long as the patient is well controlled on thyroid replacement hormones.Xx_NEWLINE_xXPatients having received any prior BCL2 inhibitor therapyXx_NEWLINE_xXHas received prior treatment with PT2977 or another HIF-2? inhibitorXx_NEWLINE_xXNo platelet inhibitor drugs within 5 days prior to infusion and during the immediate study 6 Day follow-up period.Xx_NEWLINE_xXPatients who have received a prior inhibitor of vascular endothelial growth factor (VEGF) signaling inhibitor, or a poly adenosine diphosphate-ribose polymerase (PARP) inhibitor administeredXx_NEWLINE_xXPrior therapy with a PI3K delta inhibitorXx_NEWLINE_xXPatients requiring treatment with a RANKL inhibitor (e.g. denosumab) who cannot discontinue it before treatment with atezolizumabXx_NEWLINE_xXSubjects with Ph+ disease are eligible if they are intolerant to tyrosine kinase inhibitor (TKI) therapy, or if they have relapsed/refractory disease despite treatment with at least 2 different TKIsXx_NEWLINE_xXPrior treatment with a poly (adenosine diphosphate [ADP] ribose) polymerase (PARP) inhibitorXx_NEWLINE_xXArm B: MBC with progression during or following one prior endocrine based systemic therapy in the metastatic setting, with no prior therapy with any cyclin-dependent kinase (CDK) inhibitor;Xx_NEWLINE_xXArm C: MBC with progression during or following one or two prior endocrine based systemic therapies in the metastatic setting, and following prior therapy with a CDK inhibitor.Xx_NEWLINE_xXPrior treatment with a mechanistic target of rapamycin (mTOR) inhibitor or phosphoinositide 3-kinase (PI3K) inhibitor.Xx_NEWLINE_xXPrior therapy with a MEK inhibitorXx_NEWLINE_xXPrevious mitogen-activated protein kinase kinase (MEK) inhibitor use such as PD-0325901; CI1040; AS73026; GDC 0973; ARRY43182; GSK110212Xx_NEWLINE_xXPrior treatment with a BRAF inhibitor such as vemurafenib or dabrafenib (previous treatment with sorafenib is allowed)Xx_NEWLINE_xXSubject has received a prior targeted IDH2 inhibitorXx_NEWLINE_xXMay have received prior hormonal therapy in the context of definitive treatment of a primary tumor\r\n* Patients may have had one prior systemic non-chemotherapeutic treatment (i.e. immunotherapy, receptor tyrosine kinase inhibitor, antiangiogenic agent, differentiating agent) for recurrent or metastatic diseaseXx_NEWLINE_xXHave previously received an indoleamine- 2,3-dioxygenase (IDO) inhibitor.Xx_NEWLINE_xXFailure to recover from prior side effects of immune checkpoint inhibitor therapy to =< grade 1; NOTE: Patients will not be excluded for adrenal insufficiency or hypothyroidism secondary to immunotherapy provided they are receiving hormonal replacementXx_NEWLINE_xXPrevious treatment with epacadostat, SD-101, or any other IDO inhibitor or CpG moleculeXx_NEWLINE_xXUse of any UGT1A9 inhibitor while on active study treatment, including the following: diclofenac, imipramine, ketoconazole, mefenamic acid, and probenecidXx_NEWLINE_xXThe participant has received a prior c-Met inhibitorXx_NEWLINE_xXEligible patients with germline or somatic BRCA mutations must have disease progression after treatment with a PARP inhibitor; patients with unknown BRCA status must undergo testing prior to enrollment; however, non-mutation patients will also be eligible for studyXx_NEWLINE_xXPrior exposure to a bromodomain inhibitor, such as OTX-015 or CPI-0610Xx_NEWLINE_xXHas received prior therapy with a PI3K-inhibitor (prior therapy with a PI3K-inhibitor is allowed if it was discontinued for intolerance)Xx_NEWLINE_xXPrevious use of abiraterone acetate or other investigational CYP17 inhibitor (e.g., TAK-700).Xx_NEWLINE_xXAny previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab or an anti-CTLA4 inhibitor including tremelimumabXx_NEWLINE_xXPatients must not have received prior JAK1 inhibitor therapy.Xx_NEWLINE_xXPatients who have received any checkpoint inhibitor, including ipilimumab, nivolumab, pembrolizumab or others.Xx_NEWLINE_xXImmune checkpoint inhibitor therapy within 30 days of first dose of study treatment.Xx_NEWLINE_xXPatients must have experienced disease progression within 13 months prior to study registration or experienced intolerable side effects on a tyrosine kinase inhibitor. No progression is required for patients with anaplastic thyroid cancer.Xx_NEWLINE_xXAny line of prior treatment for patients under 65 years (y), over 65y must have at least one prior line of tyrosine kinase inhibitor (TKI) treatment (excluding anaplastic patients).Xx_NEWLINE_xXPrior use of an FGFR inhibitorXx_NEWLINE_xXMore than 2 lines of chemotherapy in the metastatic setting; no limit on endocrine therapy lines; prior exposure to CDK4/6 inhibitor acceptableXx_NEWLINE_xXPrior treatment with idelalisib, other selective PI3K? inhibitors, or a pan PI3K inhibitor.Xx_NEWLINE_xXPrior treatment with MEK inhibitorXx_NEWLINE_xXPrior MEK inhibitor therapy is allowedXx_NEWLINE_xXPatients unable to tolerate checkpoint inhibitor therapyXx_NEWLINE_xXPatients with activating EGFR mutation or ALK rearrangement which is expected to be responsive to available tyrosine kinase inhibitor therapy, must have been previously treated with an applicable tyrosine kinase inhibitorXx_NEWLINE_xXPatients having received any prior BCL2 inhibitor therapyXx_NEWLINE_xXReceipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 14 days before the first dose of study treatmentXx_NEWLINE_xXPrior PARP inhibitor-based therapyXx_NEWLINE_xXPrior treatment with a MAP-kinase pathway inhibitor (RAS, RAF, ERK, MEK)Xx_NEWLINE_xXPatient must have received prior systemic therapy with an immune checkpoint inhibitor (monotherapy or combination) as 1st or 2nd line RCC treatment. Note: patients with prior mTOR inhibitor or TKI treatment as monotherapy or in combination with immune checkpoint inhibitor are allowed; however, treatment with immune checkpoint inhibitor (monotherapy or in combination) must have been the last treatment prior to study entry.Xx_NEWLINE_xXLast dose of immune checkpoint inhibitor therapy must have been received 4 or more weeks before start of study treatmentXx_NEWLINE_xXPrior treatment with bevacizumab that was not given in combination with immune checkpoint inhibitor therapy.Xx_NEWLINE_xXPrior therapy with T-cell therapy, including an immune checkpoint inhibitorXx_NEWLINE_xXFor the expansion cohorts only: prior treatment with any MEK inhibitor is not allowed in the expansion cohortsXx_NEWLINE_xXMost recent prior regimen was a PD-1 inhibitor (nivolumab or pembrolizumab) with progression; last dose must have been delivered within 90 days of enrollmentXx_NEWLINE_xXHas previously received a btk inhibitor and had progressive disease during therapy; patients who have previously discontinued btk inhibitor therapy because of intolerance may be considered for eligibility per the assessment of the PI and treating physician if there is reason that the patient may better tolerate btk inhibitor therapy at enrollment versus previouslyXx_NEWLINE_xXSubjects who are required to use a medication classified as a strong CYP3A inducer of inhibitorXx_NEWLINE_xXHas taken valproic acid, or another histone deacetylase inhibitor, within 2 weeks prior to study day 1Xx_NEWLINE_xXPrior chemotherapy, radiation (other than short cycle of radiation to reduce bone pain), treatment with a VEGF inhibitor, PARP inhibitor or immunotherapy within 21 days of first receipt of study drug. Hormone therapy within 14 days of first receipt of study drug.Xx_NEWLINE_xXReceived a prior CDK4/6 inhibitorXx_NEWLINE_xXPrior treatment with venetoclax or other Bcl-2 inhibitorXx_NEWLINE_xXCancer chemotherapy within 2 weeks before start of protocol-specified therapy, with the exception of intrathecal chemotherapy, dexamethasone, and oral small molecule inhibitors such as BTK-inhibitor, PI3K-inhibitor, or Bcl-2-inhibitor, which are allowed until the start of protocol-specified therapy). In addition, any subject whose organ toxicity (excluding hematologic) from prior treatment has not resolved to no more than Common Terminology Criteria for Adverse Events (CTCAE) grade 1.Xx_NEWLINE_xXPrior treatment with JAK2 inhibitor therapy is not excluded; a JAK2 inhibitor will need to be stopped 1-2 days prior to starting conditioning regimenXx_NEWLINE_xXPrior therapy with selumetinib or another specific mitogen-activated protein kinase kinase (MEK) inhibitor is not permittedXx_NEWLINE_xXPrevious MEK, retrovirus associated sequence (RAS), or RAF inhibitor useXx_NEWLINE_xXChemotherapy, tyrosine kinase inhibitor, or radiation therapy within 4 weeksXx_NEWLINE_xXPrevious treatment with an mTOR inhibitorXx_NEWLINE_xXConcomitant use of a UGT1A1 inhibitor, such as idinavir, atazanavir and sorafenib, throughout the study period.Xx_NEWLINE_xXMust have progression of disease within 6 months of study enrollment after treatment with only one of the following:\r\n* Two prior lines of therapy: a VEGF inhibitor (other than axitinib), followed by a single agent PD-1/PDL-1 antibody, or\r\n* One prior line of therapy: combination of a VEGF inhibitor (other than axitinib) AND a PD1/PDL1 antibody, orXx_NEWLINE_xXPrior treatment with an mTOR inhibitor (including, but not limited to, everolimus, temsirolimus, sirolimus, and ridaforolimus)Xx_NEWLINE_xXPrior treatment with a BRAF inhibitor or a MEK inhibitor; treatment by localized radiotherapy is not an exclusion criterion if an interval of at least two weeks between the end of radiotherapy and initiation of protocol therapy is observedXx_NEWLINE_xXPrior treatment with an ALK, ROS1 or MET inhibitorXx_NEWLINE_xXPHASE II DOSE EXPANSION COHORTS: \r\n* Documented ALK-­rearranged stage IIIB or IV NSCLC and:\r\n** Cohort A: No prior ALK inhibitor therapy (prior chemotherapy or immunotherapy is allowed)\r\n** Cohort B: Prior treatment with crizotinib and documented disease progression by RECIST 1.1 criteria\r\n** Cohort C: Prior treatment with 2nd generation ALK inhibitor (ALKi) (e.g. ceritinib, alectinib, loratinib, or brigatinib) and documented disease progression by RECIST 1.1 criteriaXx_NEWLINE_xXReceipt of the tyrosine kinase inhibitor sunitinib within 90 days before the first dose of study therapyXx_NEWLINE_xXIf the diagnosis is MPN-AP/BP, must have progressive/resistant disease after treatment with a DNMT1 inhibitor therapy (azacytidine, decitabine) as determined by the treating investigatorXx_NEWLINE_xXAny number of prior systemic treatment regimen in the advanced/metastatic setting is allowed (cytokine, anti-angiogenic, mTOR inhibitor or clinical trial) including previously untreated patientsXx_NEWLINE_xXAcceptable marrow function and hematologic indices for PD1/PDL1 immune checkpoint inhibitor and nelfinavir as per standard of careXx_NEWLINE_xXAllergy or intolerance to nelfinavir or selected PD1/PDL1 immune checkpoint inhibitorXx_NEWLINE_xXPrior oral anti-androgen (e.g. bicalutamide, nilutamide, enzalutamide, apalutamide), or androgen synthesis inhibitor (e.g. abiraterone, orteronel) in the past 6 months; 5-alpha reductase inhibitor therapy (e.g. finasteride, dutasteride) is allowed, as long as subject has been stable on medication for past 6 monthsXx_NEWLINE_xXAny previous treatment with PARP inhibitor, including olaparibXx_NEWLINE_xXSubjects who have previously received JAK inhibitor therapyXx_NEWLINE_xXPrior treatment with a selective PI3K? inhibitor or a pan PI3K inhibitor.Xx_NEWLINE_xXPrior treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus)Xx_NEWLINE_xXAny previous treatment with adoptive T cells therapy, a PD1 or PDL1 inhibitor, including durvalumab or any anti-CTLA4 therapy, including tremelimumab.Xx_NEWLINE_xXMetastatic renal cell carcinoma\r\n* During Phase I - All prior treatments or none are allowed\r\n* During Phase II/Cohort A - No prior treatments are allowed\r\n* During Phase II/Cohort B - Must have at least one prior treatment with a PD1 inhibitorXx_NEWLINE_xXPatient has had previous treatment with poziotinib or any other EGFR or HER2 exon 20 insertion mutation tyrosine kinase inhibitor prior to study participationXx_NEWLINE_xXPrior therapy with any cyclin-dependent kinase (CDK) inhibitorXx_NEWLINE_xXReceipt of 2, but not more that 3 prior lines of therapy that must have included a proteasome inhibitor (PI) and immunomodulatory drug (IMiD) (alone or in combination, and are refractory to the last line of treatment(Cohort D2)Xx_NEWLINE_xXTreatment with a receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor (e.g. denosumab) within 2 weeks of first study doseXx_NEWLINE_xXPrior treatment with a BRAF inhibitorXx_NEWLINE_xXScenario 1: No prior cdk 4/6 inhibitor; if patient has not previously received letrozole, letrozole will be supplied by Novartis; if previously progressed on letrozole, another aromatase inhibitor that the patient has not previously received is allowed, per standard of care (anastrazole or exemestane, not supplied by study); ribociclib will be supplied by Novartis; if patient has previously received letrozole, anastrazole, and exemestane, (s)he is not eligible; for scenario 1, patients are allowed to have started the aromatase inhibitor within 4 consecutive weeks prior to protocol registration; for instance, it is acceptable for patient who will be treated with letrozole in scenario #1, to have started letrozole within 4 consecutive weeks prior to protocol registration; no prior fulvestrant allowedXx_NEWLINE_xXScenario 2: the patient must have received an aromatase inhibitor or tamoxifen plus palbociclib as standard of care or received a CDK4/6 inhibitor (palbociclib or ribociclib or abemaciclib) as part of a clinical trial, and demonstrated evidence of disease progression; if the patient was enrolled in a randomized clinical trial involving ribociclib or abemaciclib or palbociclib (such as the MONALEESA or PALOMA series of trials), then it must be known after study discontinuation and unblinding that the patient received the investigational drug and not placebo; documentation of progression and duration of response on aromatase inhibitor or tamoxifen plus CDK 4/6 inhibitor should be provided whenever possible; no prior fulvestrant allowedXx_NEWLINE_xXPatients who have received prior inhibitor of VEGF signaling and a poly (ADP-ribose) polymerases (PARP) inhibitor administered in combination; unless administered in combination, patients who received a prior PARP inhibitor or a prior VEGF-signaling inhibitor agent are allowed after discussing with the PIXx_NEWLINE_xXPrior or concurrent treatment with AR antagonists or CYP17 enzyme inhibitor.Xx_NEWLINE_xXSubjects who received a strong cytochrome P 450 3A (CYP3A) inhibitor within 7 days prior to the first dose of ibrutinib or subjects who require continuous treatment with a strong CYP3A inhibitorXx_NEWLINE_xXSubjects may have received up to 2 prior lines of systemic therapy (excluding any neoadjuvant/adjuvant therapy) including anti-VEGF or VEGFR inhibitor (e.g. sorafenib, pazopanib, sunitinib, bevacizumab, axitinib) or mTOR inhibitor (e.g. everolimus or temsirolimus) for metastatic diseaseXx_NEWLINE_xXPrior erlotinib, gefitinib or lapatinib therapy or prior exposure to any investigational EGFR or panErbB reversible or irreversible inhibitor or any prior panitumumab or investigational EGFR-directed monoclonal antibodyXx_NEWLINE_xXTreatment with ruxolitinib or other JAK inhibitor in the pastXx_NEWLINE_xXA known P-glycoprotein (P-gp) inhibitor or inducer. Subjects who are taking such medications but who are otherwise eligible may be enrolled if they discontinue the medication ?1 week before dosingXx_NEWLINE_xXFor subjects in Groups B or C, previous use of at least one androgen pathway inhibitor (either abiraterone acetate or enzalutamide) for metastatic CRPCXx_NEWLINE_xXPatients who have previously been treated with avelumab (or another PD1/PDL1 inhibitor) in combination with 5-azacytidine will be excludedXx_NEWLINE_xXCurrently on a leukotriene inhibitor or used within the past 6 monthsXx_NEWLINE_xXPatients must be receiving treatment or planning to start treatment with a tyrosine kinase inhibitor targeting the activated geneXx_NEWLINE_xXAnticipated ribonuclease inhibitor (RAI) treatment within 18 weeks of treatmentXx_NEWLINE_xXPatient who is on strong inducer/inhibitor of CYP3A needs to be off the medication prior to treatment initiation unless it is medically necessary for the patientXx_NEWLINE_xXPatient who received any CDK4/6 inhibitorXx_NEWLINE_xXPrevious chemotherapy except for antiangiogenic agent or tyrosine kinase inhibitor (TKI) will be allowed as long as it is more than 5 yearsXx_NEWLINE_xXPrior therapy with any HER2 directed tyrosine kinase inhibitor (TKI) (e.g., lapatinib, afatinib, dacominib, neratinib, capecitabine) or anti-EGFR antibody therapy (e.g., cetuximab)Xx_NEWLINE_xXPrior treatment with a poly (adenosine diphosphate [ADP] ribose) polymerase (PARP) inhibitorXx_NEWLINE_xXPrior refractoriness to proteasome inhibitor or immunomodulatory drugs (IMiD)Xx_NEWLINE_xXPatients are excluded if they have a history of prior treatment with ipilimumab or CTLA-4 inhibitor.Xx_NEWLINE_xXPrior treatment with a Wee1 inhibitor or any irinotecan containing regimenXx_NEWLINE_xXHas received prior therapy with an EGFR tyrosine kinase inhibitor (such as erlotinib, gefitinib, afatinib, rociletinib, or AZD9291) for NSCLCXx_NEWLINE_xXThe patient has received chemotherapy, surgery, radiotherapy (for therapeutic purposes), tyrosine kinase inhibitor (TKI) (e.g. erlotinib, gefitinib), investigational drugs, chronic use of systemic corticosteroids or statin therapy within 2 weeks prior to leukapheresis.Xx_NEWLINE_xXPatients with a history of tamoxifen and/or aromatase inhibitor use for treatment or prevention are eligible but should discontinue these medications at least 2 weeks prior to starting this trialXx_NEWLINE_xXPrior treatment\r\n* No more than two prior chemotherapy regimens in the metastatic setting\r\n* Prior treatment with fulvestrant in the metastatic setting is required, except for patients with a history of ER-negative metastatic breast cancer\r\n* Unlimited prior endocrine therapy regimens in the metastatic setting are allowed\r\n* No prior treatment with an aurora Kinase inhibitor (either an aurora A or pan-aurora kinase inhibitor)Xx_NEWLINE_xXNot receiving administration of proton pump inhibitor, H2 antagonist, or pancreatic enzymesXx_NEWLINE_xXNo requirement for constant administration of proton pump inhibitor, H2 antagonist, or pancreatic enzymesXx_NEWLINE_xXPatients who have received prior treatment with a selective CDK4 inhibitorXx_NEWLINE_xXPrior treatment with nivolumab or any other PD1/PDL1 checkpoint inhibitorXx_NEWLINE_xXPrior treatment with selumetinib or another specific MEK 1/2 inhibitorXx_NEWLINE_xXFor patients with Philadelphia chromosome positive (Ph+) disease, have previously received treatment with >= 1 Abelson (ABL) kinase inhibitor (e.g., imatinib, dasatinib, etc.) or are ineligible for such treatmentXx_NEWLINE_xXHas received prior therapy with any immune checkpoint inhibitorXx_NEWLINE_xXPrior aromatase inhibitor therapy first initiated > 4 weeks prior to study enrollmentXx_NEWLINE_xXPrior treatment:\r\n* Patients must not have received chemotherapy, radiation or surgical resection of malignancy within 3 weeks prior to the start of study drug; however, if they have received nitrosourea or mitomycin C then they should not be enrolled in the study until 6 weeks after therapy was last received\r\n* No limitations to number of prior therapies\r\n* Prior treatment with volasertib or any PLK1 inhibitor\r\n* Prior treatment with a histone deacetylase inhibitor (anti-epileptics ok)Xx_NEWLINE_xXPrior exposure to T cell checkpoint inhibitor therapies, including durvalumab and tremelimumabXx_NEWLINE_xXTreatment-naive and previously treated patients will be included; however, patients may not have received a BRAF, MEK or HSP90 inhibitor in the pastXx_NEWLINE_xXSubjects previously treated with BRAF, MEK or HSP90 inhibitor therapyXx_NEWLINE_xXPatients who received a prior selective FGFR inhibitor in the recurrent/metastatic disease setting; prior use of a multikinase inhibitor that includes anti-FGFR activity is acceptable after review by the lead investigator (Dr. Seiwert)Xx_NEWLINE_xXPrevious CDK4/6 inhibitorXx_NEWLINE_xXDiagnosis of Philadelphia chromosome (Ph)-positive or BCR-ABL positive CML in early chronic phase CML (i.e., time from diagnosis is 12 months); except for hydroxyurea, patients must have received no or minimal prior therapy, defined as < 1 month (30 days) of prior Food and Drug Administration (FDA) approved tyrosine kinase inhibitor (TKI)Xx_NEWLINE_xXPrior treatment with nintedanib or any other vascular endothelial growth factor receptor (VEGFR) inhibitor, with the exception of treatment of prior malignancies with a VEGFR inhibitorXx_NEWLINE_xXPatients who received prior treatment with a selective FGFR inhibitorXx_NEWLINE_xXSubjects with disease recurrence or progression After therapy with an immune checkpoint inhibitor and platinum-based chemotherapy i) either 1st line chemotherapy followed by 2nd line checkpoint inhibitor, or ii) 1st line combination of checkpoint inhibitor and chemotherapyXx_NEWLINE_xXPatients whose tumor harbors EGFR gene mutation that sensitizes tumors to Tyrosine-Kinase Inhibitor (TKI) (EGFR exon 18-21) or Anaplastic Lymphoma Kinase (ALK) rearrangement.Xx_NEWLINE_xXPatients with solid tumors as described below:\r\n* Inoperable or metastatic (advanced) melanoma:\r\n** Has received, is intolerant, or refused a CTLA-4 inhibitor (ipilimumab) or a PD-1 inhibitor (nivolumab or pembrolizumab) as monotherapy and/or a combination of ipilimumab and nivolumab\r\n** Has received or is intolerant of a BRAF inhibitor or the combination of BRAF and MEK inhibitors for BRAFv600 mutant melanoma and a PD-1 inhibitor as monotherapy or in combination\r\n* Inoperable or metastatic (advanced) ovarian, primary peritoneal or fallopian tube carcinoma:\r\n** Has received platinum containing chemotherapy and has platinum refractory or resistant disease that has progressed on second line therapy\r\n** If platinum sensitive disease, should have received >= 2 lines of chemotherapy\r\n** May have received PARP inhibitors, bevacizumab or other targeted VEGF inhibitor therapy\r\n* Inoperable or metastatic (advanced) synovial sarcoma:\r\n** Should have received and progressed on >= two lines of systemic therapy\r\n* Subjects with other histologies:\r\n** Must have previously received two lines of systemic standard care (or effective salvage chemotherapy regimens) for metastatic disease, if known to be effective for that disease, and have been deemed either non-responders (progressive disease) or have recurredXx_NEWLINE_xXOne of the following:\r\n* Documentation of BRAF V600E mutation and inability to access BRAF inhibitor or prior treatment with a BRAF inhibitor discontinued due to intolerable side effects or toxicity prior to progression OR\r\n* Documentation of wild-type BRAF V600 mutational statusXx_NEWLINE_xXPrior treatment with a mitogen-activated protein kinase kinase (MEK) inhibitorXx_NEWLINE_xXPatients taking any histone deacetylase inhibitor (HDACi) other than vorinostatXx_NEWLINE_xXPrior treatment with an mTOR, AKT, or PI3K inhibitorXx_NEWLINE_xXPrevious treatment with any MEK inhibitorXx_NEWLINE_xXPrior treatment with vemurafenib or other BRAF inhibitor within 42 days of Study Day 1 of Period AXx_NEWLINE_xXPatient has had prior toxicity from a CDK 4/6 inhibitor necessitating discontinuation of the drug; patient may have had prior treatment with a cdk 4/6 inhibitor in the adjuvant or metastatic settingXx_NEWLINE_xXPatients with Philadelphia chromosome positive (Ph+) ALL are eligible if they are intolerant to or have failed tyrosine kinase inhibitor therapyXx_NEWLINE_xXAZD1775 is an inhibitor of breast cancer resistance protein (BCRP); the use of statins including atorvastatin which are substrates for BCRP are therefore prohibited and patients should be moved on to non-BCRP inhibitor alternativesXx_NEWLINE_xXSubjects with prior treatment with an MDM2 inhibitorXx_NEWLINE_xXSubjects must have relapsed or refractory disease after either one of the following:\r\n* At least 3 prior regimens, which must have contained an alkylating agent, proteasome inhibitor, and immunomodulatory agent (IMiD)\r\nOR\r\n* At least 2 prior regimens if “double-refractory” to a proteasome inhibitor and IMiD, defined as progression on or within 60 days of treatment with these agents; Note: induction therapy, stem cell transplant, and maintenance therapy, if given sequentially without intervening progression, should be considered as 1 “regimen”Xx_NEWLINE_xXPatients with no prior ALK-inhibitor therapy will be placed in cohort A, those treated with one prior line of ALK-inhibitor (at any time) will enter cohort BXx_NEWLINE_xXPrior treatment with crizotinib, or any other cMET or HGF inhibitorXx_NEWLINE_xXPrior treatment with an mechanistic target of rapamycin (mTOR) inhibitor or phosphatidylinositol-3-Kinase (PI3K) inhibitor is allowed but not requiredXx_NEWLINE_xXPrior treatment with any cyclin dependent kinase (CDK) inhibitorXx_NEWLINE_xXReceipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 14 days before the first dose of study treatment; note: subjects with prostate cancer currently receiving luteinizing hormone-releasing hormone (LHRH) or gonadotropin-releasing hormone (GnRH) agonists may be maintained on these agentsXx_NEWLINE_xXAny previous treatment with a PARP inhibitor, including OlaparibXx_NEWLINE_xXPrior systemic therapy with a small molecule oral kinase inhibitor, including but not limited to: pazopanib, sunitinib, sorafenib, everolimus, sirolimus, vemurafenib, dasatinib and trametinibXx_NEWLINE_xXProgression of disease on hedgehog inhibitor (HHI) therapy or intolerance of prior HHI therapyXx_NEWLINE_xXAny previous use of Janus kinase (JAK) inhibitor, osimertinib, or other EGFR-directed therapy for T790M-mt NSCLC.Xx_NEWLINE_xXHas been previously treated with a cyclin-dependent kinase (CDK) inhibitorXx_NEWLINE_xXHas had prior exposure to tazemetostat or other inhibitor(s) of enhancer of zeste homologue-2 (EZH2)Xx_NEWLINE_xXA strong or moderate CYP3A inhibitor or inducer within 7 daysXx_NEWLINE_xXAny prior treatment with either a MEK, Ras, or Raf inhibitor for advanced or metastatic NSCLC.Xx_NEWLINE_xXPrior therapy with any PARP inhibitor, including olaparibXx_NEWLINE_xXPatients with Philadelphia chromosome positive (Ph+) ALL can be enrolled in CR1 or CR2 and beyond; a tyrosine kinase inhibitor (TKI) will be added at the discretion of the treating physician; MRD for these patients will be defined by PCR of 0.1% and above (International Scale).Xx_NEWLINE_xXPatients may not have previously received a PARP inhibitorXx_NEWLINE_xXStage 4 non-squamous cell lung cancer that has not been treated previously with systemic chemotherapy or bevacizumab, but may have received prior targeted treatment (e.g., alk1 inhibitor)Xx_NEWLINE_xXPrior treatment with a PARP inhibitorXx_NEWLINE_xXPatients who have received prior therapy with an irinotecan-based or temozolomide-based regimen are eligible; patients who have received prior therapy with a PARP inhibitor other than talazoparib are eligible; however, patients who have progressed on a PARP inhibitor plus irinotecan regimen are not eligibleXx_NEWLINE_xXPrior receipt of an indoleamine 2,3-dioxygenase (IDO) inhibitorXx_NEWLINE_xXPrior BTK inhibitor treatment.Xx_NEWLINE_xXPrevious treatment with a c-MET inhibitor or HGF-targeting therapy (applies only to Group 2)Xx_NEWLINE_xXPrior treatment with an MDM2 inhibitor.Xx_NEWLINE_xXPatients should not have taken valproic acid or another histone deacetylase inhibitor for at least 2 weeks prior to enrollmentXx_NEWLINE_xXReceipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 14 days before the first dose of study treatmentXx_NEWLINE_xXPART 2: Received JAK inhibitor for at least 8 weeks immediately prior to conditioning and be able to continue until Day -4 pre-transplantXx_NEWLINE_xXPrevious therapy with T-DM1 or any HER2 tyrosine kinase inhibitor (TKI) including neratinib for any malignancy.Xx_NEWLINE_xXPrior treatment with any VEGFR tyrosine kinase inhibitorXx_NEWLINE_xXConcurrent use of the selective serotonin reuptake inhibitor (SSRI) antidepressant fluvoxamine (Luvox)Xx_NEWLINE_xXPatients who have received prior treatment with a phosphoinositide 3-kinase (P13K) inhibitorXx_NEWLINE_xXPrior therapy is allowed; patients may have received any number of prior lines of therapy, including treatment with a BRAF and/or MEK inhibitorXx_NEWLINE_xXPatients must not have received prior HSP90 inhibitor therapyXx_NEWLINE_xXPatients must be at least 2 weeks from last treatment with a proteasome inhibitor (e.g., bortezomib, carfilzomib) at time of treatment on this protocolXx_NEWLINE_xXA history of prior treatment with ipilimumab or prior CD137 agonist or cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitor or agonistXx_NEWLINE_xXPrior therapy with a MEK inhibitorXx_NEWLINE_xXBeginning adjuvant aromatase inhibitor therapy, with no previous use within the last 6 weeksXx_NEWLINE_xXAny patient with metastatic melanoma from any site whose tumor is BRAF V600E mutation (V600EBRAF) positive, regardless of prior treatment will be eligible; these include untreated patients or those treated with chemotherapy, biochemotherapy or a prior BRAF-inhibitorXx_NEWLINE_xXPrior use of MEK162 or concurrent use of other approved anticancer or investigational agents is not allowed; patients treated with prior EGFR tyrosine kinase inhibitor (TKI) therapy (including erlotinib) are allowed to enrollXx_NEWLINE_xXPrior bevacizumab or tyrosine-kinase inhibitorXx_NEWLINE_xXPatients taking a potent CYP3A4 inhibitor that cannot be changed to an alternate drug.Xx_NEWLINE_xXPrimary patient samples must show in vitro kinase inhibitor sensitivity as determined by the Oregon Health and Science University (OHSU) functional kinase inhibitor screen; for OHSU patients, functional kinase inhibitor screening may be performed as part of this study or through enrollment in eIRB4422 if the identical Food and Drug Administration (FDA)/Clinical Laboratory Improvement Act (CLIA) approved assay is used and a result is available within 2 weeks of starting on study drug treatmentXx_NEWLINE_xXPrevious treatment with PI3K inhibitors, AKT inhibitors, mTOR inhibitor or fulvestrantXx_NEWLINE_xXPatients who have received prior treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus)Xx_NEWLINE_xXAny previous treatment with PARP inhibitor, including olaparib.Xx_NEWLINE_xXUnacceptable toxicity with prior checkpoint inhibitorXx_NEWLINE_xXPrior receipt of a selective FGFR inhibitor.Xx_NEWLINE_xXUse of 5 alpha reductase inhibitor within 1 month of screening or total use, within the last two years prior to screening, of >3 monthsXx_NEWLINE_xXFor the bortezomib arm of the study, prior therapy with a proteasome inhibitor if discontinued due to toxicityXx_NEWLINE_xXHave received ? 2 lines of prior therapy which must have included an immune modulatory drug (IMiD) and a proteasome inhibitor alone or in combinationXx_NEWLINE_xXHave not received a tyrosine kinase inhibitor (TKI) with activity against the specific documented EGFR exon 20 insertion.Xx_NEWLINE_xXReceived a potent CYP3A inhibitor within 7 days or potent CYP3A inducer within 5 weeks prior to first dose of AP32788.Xx_NEWLINE_xXPrior receipt of a PIM inhibitorXx_NEWLINE_xXReceived any previous treatment with alvocidib or any other CDK inhibitorXx_NEWLINE_xXTreatment with chemotherapy or targeted therapy (e.g. tyrosine kinase inhibitor) =< 28 days prior to registrationXx_NEWLINE_xXPrior treatment with an FTase inhibitorXx_NEWLINE_xXFor Parts A, B, D, E, and F: Have previously received treatment with any cyclin dependent kinase 6 (CDK6) inhibitor. For Part C participants may have received prior palbociclib or ribociclib, but not abemaciclib treatment.Xx_NEWLINE_xXPatients who have received a prior mammalian target of rapamycin (mTOR) inhibitorXx_NEWLINE_xXPrior treatment with more than 1 checkpoint inhibitor (combination); prior treatment with a lymphocyte-activation gene 3 (LAG-3) inhibitor; prior treatment with multi specific checkpoint inhibitor molecules;Xx_NEWLINE_xXPrior treatment with a poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitorXx_NEWLINE_xXHave an EGFR or ALK genomic tumor aberrations for which targeted therapy with an EGFR or ALK inhibitor is indicated. Additional Exclusion Criteria for Cohort 2:Xx_NEWLINE_xXPrior treatment with ASN007 or another ERK1/2 inhibitorXx_NEWLINE_xXPart B: Prior treatment with a RAF or MEK pathway inhibitor, except BRAFmutant melanoma (Group 1)Xx_NEWLINE_xXPhase 1: Relapsed MM with at least one prior line of therapy and should have received a proteasome inhibitor and an immunomodulatory drugXx_NEWLINE_xXPhase 2: 1-3 prior lines of therapy and should have received a proteasome inhibitor and an immunomodulatory drugXx_NEWLINE_xXAdministration of a strong or moderate CYP3A inhibitor or inducer =< 14 days prior to registrationXx_NEWLINE_xXPhiladelphia chromosome positive (Ph+) B-cell ALL eligible for tyrosine kinase inhibitor therapyXx_NEWLINE_xXPatients who have received prior treatment with an mTOR inhibitorXx_NEWLINE_xXPrior treatment with idelalisib (a PI3K inhibitor).Xx_NEWLINE_xXPrior treatment with an antibody-drug conjugate (ADC) which consists of an exatecan derivative that is a topoisomerase I inhibitor (eg, DS-8201)Xx_NEWLINE_xXPrior treatment with any Hsp90 inhibitor.Xx_NEWLINE_xXPrior treatment with crizotinib or any other cMET or HGF inhibitorXx_NEWLINE_xXPrior treatment with any Hsp90 inhibitor.Xx_NEWLINE_xXPrior use of trametinib or other MAPK inhibitor in any contextXx_NEWLINE_xXPrior treatment with phosphatidylinositol 3-kinase (PI3K) delta inhibitors, Bruton's tyrosine kinase (BTK) inhibitors, janus kinase inhibitor (JAK) inhibitors, mammalian target of rapamycin (mTOR) inhibitors, or spleen tyrosine kinase (Syk) inhibitorsXx_NEWLINE_xXPart E: Prior treatment with a PI3K/mTOR inhibitorXx_NEWLINE_xXPrevious treatment with an histone deacetylase inhibitor or an epidermal growth factor receptor inhibitor within at least 4 weeks of the date of first administration of study drugXx_NEWLINE_xXPrior or current treatment with a FGFR inhibitorXx_NEWLINE_xXPatients who have had prior exposure to romidepsin or any proteasome inhibitor are NOT eligible for participationXx_NEWLINE_xXPatient must have received ? 2 prior anti-myeloma regimens including a proteasome inhibitor and/or immunomodulatory agent.Xx_NEWLINE_xXPatients with known and documented EGFR mutation who have not received an EGFR inhibitor.Xx_NEWLINE_xXPrior treatment with hsp90 inhibitorXx_NEWLINE_xXNo history of prior treatment with ipilimumab or prior tumor necrosis factor receptor superfamily, member 9 (CD137) agonist or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor or agonistXx_NEWLINE_xXPatients who have received prior treatment with a P13K inhibitorXx_NEWLINE_xXPatients who have received therapy with an oral tyrosine kinase inhibitor (eg, erlotinib) within 14 days prior to entry into the protocol.Xx_NEWLINE_xXNeed to continue any regularly-taken medication that is a potent inhibitor or inducer of the CYP3A pathway or P-glycoprotein activityXx_NEWLINE_xXLess than 2 weeks since use of a medication or ingestion of an agent, beverage, or food that is a potent inhibitor or inducer of the CYP3A pathway or P-glycoprotein activityXx_NEWLINE_xXPrior treatment with a tyrosine kinase c-kit inhibitorXx_NEWLINE_xXNeed to continue any regularly-taken medication that is a potent inhibitor or inducer of the CYP3A pathway or P-glycoprotein activityXx_NEWLINE_xXNeed to continue any regularly-taken medication that is a potent inhibitor or inducer of the CYP3A pathway or P-glycoprotein activityXx_NEWLINE_xXPatient with documented treatment failure of his/her handicap(s) with at least one of the following therapy used at optimized dose: Anti H1, Anti H2, Proton pump inhibitor, Osteoclast inhibitor, Cromoglycate Sodium, AntileukotrieneXx_NEWLINE_xXPrevious treatment with any Tyrosine Kinase InhibitorXx_NEWLINE_xXKnown intolerance to checkpoint inhibitor therapy, defined by the occurrence of an AE leading to drug discontinuation;Xx_NEWLINE_xXPrior treatment with an investigational EZH2 inhibitorXx_NEWLINE_xXAny previous treatment with PARP inhibitor, including olaparib.Xx_NEWLINE_xXPrevious treatment with CSF-1R kinase inhibitor or CSF-1R blocking antibody.Xx_NEWLINE_xXHas received at least 2 consecutive cycles of a proteasome inhibitor (PI).Xx_NEWLINE_xXHistory of treatment with venetoclax or another B-Cell Lymphoma (BCL)-2 inhibitor or pomalidomide.Xx_NEWLINE_xXA history of prior significant toxicity, other than thrombocytopenia, from another Bcl-2 family protein inhibitorXx_NEWLINE_xXAny previous treatment with poly-adenosine diphosphate ribose polymerase (PARP) inhibitor, including olaparibXx_NEWLINE_xXTreatment with a moderate or strong cytochrome P450 3A4 (CYP3A) inhibitor or inducer within 7 days prior to\r\nfirst dose of venetoclax or need for treatment with a strong CYP3A inhibitor or inducer during the period or the study; patients who have a need for treatment with a moderate CYP3A inhibitor or inducer during venetoclax dose escalation will also be excludedXx_NEWLINE_xXPrior treatment with a PARP inhibitor in any disease settingXx_NEWLINE_xXPrior therapy with a PARP inhibitor (e.g., olaparib, talazoparib, veliparib, niraparib, rucaparib)Xx_NEWLINE_xXPatients who have had immunotherapy or tyrosine kinase inhibitor (TKI) therapy within two weeks prior to entering the studyXx_NEWLINE_xXPrior treatment with 1 BRAF inhibitor and/or 1 MEK inhibitor allowedXx_NEWLINE_xXWilling to accept oral endocrine therapy with a third generation aromatase inhibitor (AI) or selective estrogen receptor modifier (SERM)Xx_NEWLINE_xXKnown contraindication to aromatase inhibitor or SERM therapyXx_NEWLINE_xXPrior use of aromatase inhibitor therapy apart from assisted reproductionXx_NEWLINE_xXPrior treatment with vorinostat or other HDAC inhibitorXx_NEWLINE_xXHave demonstrated progressive disease while taking a PARP inhibitor as a previous therapy. Response to prior PARPi is not required.Xx_NEWLINE_xXPrior exposure to ibrutinib or to a BCR inhibitor (eg Btk or PI3 kinase or Syk inhibitors) or a BCL-2 inhibitor (eg venetoclax)Xx_NEWLINE_xXPatients who have received prior treatment with nintedanib or any other VEGFR inhibitor are not eligibleXx_NEWLINE_xXReceipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 14 days before the first dose of study treatmentXx_NEWLINE_xXHistory of hypersensitivity to durvalumab or tremelimumab or any CTLA4, PD1, or PDL-1 inhibitorXx_NEWLINE_xXSubjects who received a strong cytochrome P 450 3A (CYP3A) inhibitor within 7 days prior to the first dose of ibrutinib or subjects who require continuous treatment with a strong CYP3A inhibitorXx_NEWLINE_xXReceived any prior poly ADP-ribose polymerase inhibitor (PARPi) treatmentXx_NEWLINE_xXNo history of prior exposure to a MEK inhibitorXx_NEWLINE_xXPrior treatment with a PARP inhibitorXx_NEWLINE_xXCurrent use of selective serotonin reuptake inhibitor (SSRI), serotonin-norepinephrine reuptake inhibitor (SNRI), monoamine oxidase (MAO) inhibitor, tramadol or trazadone; or use of these agents within 14 daysXx_NEWLINE_xXIf participant is on a selective serotonin reuptake inhibitor (SSRI), serotonin-norepinephrine reuptake inhibitor (SNRI) or membrane stabilizer (pregabalin, gabapentin, for example), it must be a stable, unchanged dose for previous 3 monthsXx_NEWLINE_xXPast treatment with any MEK or ERK inhibitor or with panitumumabXx_NEWLINE_xXPrior therapy with an Abelson murine leukemia viral oncogene homolog (ABL) kinase inhibitor such as nilotinib, ponatinib, dasatinib, or imatinibXx_NEWLINE_xXPrior MEK inhibitor or prior TAS-102 therapyXx_NEWLINE_xXHave received prior treatment with an IDH1 inhibitor.Xx_NEWLINE_xXPrior treatment for MDS with the histone deacetylase (HDAC) inhibitors Zolinza (vorinostat), Belenodaq (belinostat), Farydak (panobinostat), Istodax (romidepsin/depsipetide), or investigational agent with significant action as an HDAC inhibitor.Xx_NEWLINE_xXPrior treatment: Treated with at least three prior lines of multiple myeloma therapy including a proteasome inhibitor and an immuno modulatory agent or who are double refractory to a proteasome inhibitor and an immuno modulatory agent. Prior anti-CD38 antibody (e.g., daratumumab, isatuximab) treatment is acceptable only for participants receiving monotherapy treatment.Xx_NEWLINE_xXDocumented evidence of tumor progression on or after CDK 4/ 6 inhibitor combination treatment; CDK 4/6 inhibitor must be the last treatment regimen prior to study entry,Xx_NEWLINE_xXProgression on a prior regimen/line of an androgen synthesis inhibitor for prostate cancerXx_NEWLINE_xXPrior treatment with enzalutamide or any other newer hormonal androgen receptor inhibitor (e.g., apalutamide, ODM-201)Xx_NEWLINE_xXParticipants who have received prior treatment with a CDK4/6 inhibitorXx_NEWLINE_xXPrevious treatment with any checkpoint inhibitor such as anti-PD1 or PD-L1 agents including pembrolizumab (KEYTRUDA) or any other checkpoint inhibitor(s) (e.g., ipilimumab, nivolumab, etc.)Xx_NEWLINE_xXPhase 2 Only: Prior progression while receiving approved or investigational tyrosine kinase inhibitors targeting TRK, including entrectinib, crizotinib and lestaurtanib. Patients who received a TRK inhibitor for less than 28 days of treatment and discontinued because of intolerance remain eligible.Xx_NEWLINE_xXSubjects with prior treatment with an MDM2 inhibitorXx_NEWLINE_xXPatients requiring treatment with a RANKL inhibitor (e.g. denosumab) who cannot discontinue it before treatment with atezolizumabXx_NEWLINE_xXTREATMENT: Patients with melanoma and known v-raf murine sarcoma viral oncogene homolog B (BRAF) V600E mutations must have received and progressed on specific BRAF inhibitor therapyXx_NEWLINE_xXTREATMENT: Patients with metastatic breast cancer and BRCA mutations must have received specific PARP inhibitor therapy; if these patients have other mutations of interest as defined in the protocol, they will be eligible to receive agents based on that mutationXx_NEWLINE_xXTREATMENT: Patients who have had prior treatment with any PARP inhibitor in combination with temozolomide are ineligible to receive treatment with veliparib on this study; patients who have received prior temozolomide or PARP inhibitor with or without other chemotherapy/targeted agent aside from temozolomide should not be excluded solely because of receiving prior PARP inhibitor or temozolomide, unless it was in combination; patients who have received temozolomide with a PARP inhibitor in the past are eligible to participate but will not receive veliparib with temozolomide on study; such patients are eligible to receive other treatment regimens on study based on identified genetic mutationsXx_NEWLINE_xXPrior treatment with a PARP inhibitor or topotecanXx_NEWLINE_xXPrior treatment with a TORC1, dual TORC1/2 inhibitor, or BCL-2/xL inhibitorXx_NEWLINE_xXPrior therapies:\r\n* Patients without activating mutations and gene rearrangements should have received at least one prior chemotherapy regimen; any number of prior therapies is allowed except for immunotherapy (e.g. anti PD-1, PD-L1, vaccines, CTLA-4 etc.)\r\n* Patients with activating mutations and gene rearrangements with known documented benefit from tyrosine kinase inhibitors should have received and demonstrated progression with that inhibitor (e.g. EGFR del 19 mutation should have been treated with gefitinib, erlotinib or afatanib etc); ALK rearrangements should have been treated with an ALK inhibitor; patients who have progressed on these agents should be assessed, if appropriate, for resistance mutations susceptible to approved agents and treated with that agent\r\n* No prior gemcitabine treatmentXx_NEWLINE_xXDOSE EXPANSION COHORT: Subjects with metastatic or recurrent NSCLC who progressed on at least one line of systemic therapy for metastatic or recurrent disease, which must include anti PD-1 or PD-L1 inhibitor, and must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and accessible tumor for biopsy; molecular status of EGFR and ALK must have been assessed for nonsquamous NSCLC; those with activating EGFR mutation or ALK gene arrangement must have progressed on at least one kinase inhibitorXx_NEWLINE_xXNo previous treatment with the specific assigned study drug or any other PARP inhibitorXx_NEWLINE_xXAny previous treatment with PARP inhibitor, including olaparibXx_NEWLINE_xXPatients enrolled to the prior treatment arm of the expansion cohort must have been exposed to a tyrosine kinase inhibitor (TKI) for metastatic disease; exposure to TKI as part of (neo)adjuvant treatment that completed within 1 year of study qualifies as prior exposure as wellXx_NEWLINE_xXPatient must have relapsed or refractory disease according to international uniform response criteria and must have previously received therapy with a proteasome inhibitor and an immunomodulatory imide drug (IMiD)Xx_NEWLINE_xXPrevious MEK, RAS, or RAF inhibitor useXx_NEWLINE_xXPatients who have had prior therapy with any phosphatidylinositol 3 kinase (PI3K)/v-akt murine thymoma viral oncogene homolog 1 (AKT)/mammalian target of rapamycin (mTor) pathway inhibitorXx_NEWLINE_xXPrior treatment with a histone deacetylase inhibitorXx_NEWLINE_xXPrior poly ADP ribose polymerase (PARP) inhibitor therapy is allowed; patients with ovarian cancer and a BRCA mutation should have had prior treatment with olaparib per guidelines for standard of care treatmentXx_NEWLINE_xXIf BRAFV600-mutant, documented refractory disease to at least one BRAF inhibitor (dabrafenib or vemurafenib) and/or a MEK inhibitor (trametinib or cobimetinib), defined as progression of measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) criteria while on treatment; subjects with MAPK inhibitor-intolerance are eligible if they meet criteriaXx_NEWLINE_xXSubjects who are unable to tolerate BRAF inhibitor and/or MEK inhibitor therapy due to grade >= 2 toxicity (Common Terminology Criteria for Adverse Events [CTCAE] version [v]4.0) from these agents, irrespective of antitumor response, are eligible on condition that: (a) toxicities persisted despite change from doublet to singlet therapy (i.e. from concurrent BRAF inhibition plus MEK inhibition to BRAF inhibition alone), (b) toxicities are attributed to a class effect, and therefore switch from one drug to another is expected to induce the same type of toxicity (e.g. ocular toxicities or cardiac dysfunction from MEK inhibitor), (c) drug-specific toxicities that do not resolve with switch from one BRAF inhibitor to another (i.e. dabrafenib to vemurafenib, or vice versa), will be eligible for enrollment in 9922; in other words, patients will be allowed to enroll into the NCI9922 study despite lack of progression to MAPK inhibitor treatments, on condition that grade 2 or higher toxicities attributed to MAPK inhibitors resolve to grade 1, or less, at the time of study enrollmentXx_NEWLINE_xXSubjects who received a strong cytochrome P450 (CYP) 3A inhibitor within 7 days prior to the first dose of ibrutinib or subjects who require continuous treatment with a strong CYP 450 3A inhibitorXx_NEWLINE_xXPatients may not have previously received a PARP-inhibitorXx_NEWLINE_xXPatients who have been in the past enrolled on a study of a Cdk inhibitorXx_NEWLINE_xXPrior therapy with an angiogenesis inhibitorXx_NEWLINE_xXHistory of grade 3 or 4 bowel toxicity from immune checkpoint inhibitor within 12 weeks of registrationXx_NEWLINE_xXPrior taxane, vincristine, or other microtubule inhibitor chemotherapies for treatment of GBM or other malignancyXx_NEWLINE_xXPrior therapy with a hedgehog inhibitorXx_NEWLINE_xXPrior exposure to a Bruton agammaglobulinemia tyrosine-protein kinase (BTK) inhibitorXx_NEWLINE_xXAny previous treatment with a HDAC inhibitor, including citarinostatXx_NEWLINE_xXNo line limit on prior therapies as long as the patient meets all other eligibility criteria; patients who have received prior PARP inhibitors and/or PI3kinase inhibitors are allowed to participate on the dose escalation portion; prior PARP inhibitors and/or PI3Kinase inhibitors excludes patients from the dose expansion cohort, but TNBC patients with BRCA mutations can go on if they had previously received a PARP inhibitorXx_NEWLINE_xXTNBC participants with BRCA mutation, unless they've had prior PARP inhibitorXx_NEWLINE_xXHistory of grade 3 or 4 toxicities with previous PI3kinase inhibitor or PARP inhibitor exposure with the exception of hematologic toxicitiesXx_NEWLINE_xXThe washout period for an EGFR inhibitor is a minimum of 3 daysXx_NEWLINE_xXUse of a protease inhibitor for any indication within three months prior to start of study treatmentXx_NEWLINE_xXAny IFN- containing agent within 8 weeks prior to screening or any prior exposure to HCV-specific antivirals agent(s), other than NS3/4A protease inhibitor and sofosbuvirXx_NEWLINE_xXPrior therapy with a selective phosphoinositide 3-kinase (PI3K) inhibitor or other B-cell receptor targeting agents is allowedXx_NEWLINE_xXPatients who have been previously treated with ibrutinib (or any Bruton’s tyrosine kinase inhibitor) are eligible for the ibrutinib pre-treated cohort as long as prior ibrutinib or BTK inhibitor therapy was not discontinued due to toxicity/adverse event; there is no minimum dose of ibrutinib; any prior administration will disqualify patients for the ibrutinib-naïve cohort and will require enrollment on the ibrutinib pre-treated cohortXx_NEWLINE_xXPatients who have received prior treatment with a pan-selective PI3K inhibitor are not eligibleXx_NEWLINE_xXPrior cyclin-dependent kinase (CDK)4/6 inhibitor exposureXx_NEWLINE_xXSubject has received previous treatment with a PI3K inhibitor; exceptions may be made for subjects who discontinued treatment with a previous PI3K inhibitor for reasons other than toxicity or progression and as long as it has been > 12 months since discontinuation of the previous PI3K inhibitor; this exception will require prior approval from the study PI at KUMCXx_NEWLINE_xXPrior treatment with everolimus other than in combination with hormonal therapy for treatment of breast cancer or prior treatment with another mammalian target of rapamycin (mTOR) inhibitor (sirolimus, temsirolimus) for any indicationXx_NEWLINE_xXPatients who have received prior therapy with a temozolomide-based regimen are eligible; Note: patients who have progressed on a poly adenosine diphosphate ribose polymerase (PARP) inhibitor and temozolomide regimen are not eligible for Part A of the studyXx_NEWLINE_xXPARP inhibitor exposure:\r\n* Part A: Patients who have received prior therapy with a PARP inhibitor, with the exception of BMN 673, are eligible; however, patients who have progressed on a PARP inhibitor and temozolomide regimen are not eligible\r\n* Part B and Part C: Patients who have previously been exposed to a PARP inhibitor are not eligibleXx_NEWLINE_xXPhase 1 (Part A): patients who have progressed on a PARP inhibitor and temozolomide regimen are not eligibleXx_NEWLINE_xXPhase 2 (Part B and Part C): patients who have previously been exposed to a PARP inhibitor are not eligibleXx_NEWLINE_xXPrevious endocrine therapy such as raloxifene or tamoxifen (or other selective estrogen receptor modulator [SERM]) or an aromatase inhibitor for any malignancyXx_NEWLINE_xXMonoamine oxidase (MAO) inhibitor use within the past 3 weeks or prior evidence of serotonin syndromeXx_NEWLINE_xXPatients who have had prior therapy with GSK2141795 or any other PI3K/AKT/MTOR pathway inhibitorXx_NEWLINE_xXPatients who have prior therapy with trametinib or any other MEK inhibitorXx_NEWLINE_xXPrior therapy with another hedgehog inhibitorXx_NEWLINE_xXPatients who have had prior therapy with a MEK inhibitor or an inhibitor of mutant BRAF are ineligible; because sorafenib has low efficacy as a BRAF inhibitor, prior therapy with it is allowedXx_NEWLINE_xXPrior treatment with an mammalian target of rapamycin (MTOR) inhibitor (including everolimus, sirolimus, temsirolimus)Xx_NEWLINE_xXAny previous treatment with a PARP inhibitor, including olaparibXx_NEWLINE_xXPatients may have been previously treated for metastatic disease, or may have not had prior systemic treatment; patients with a V600 BRAF mutated tumor may have previously received a prior BRAF inhibitorXx_NEWLINE_xXPrior treatment with mTOR inhibitor or other molecularly targeted therapyXx_NEWLINE_xXPrevious BRAF inhibitor treatmentXx_NEWLINE_xXTreatment-naïve and previously treated patients will be included; however, patients may not have received a BRAF or HSP90 inhibitor in the pastXx_NEWLINE_xXSubjects previously treated with BRAF or HSP90 inhibitor therapyXx_NEWLINE_xXPatients who have received prior treatment with a known mammalian target of rapamycin (mTOR) inhibitor (sirolimus, temsirolimus, everolimus)Xx_NEWLINE_xXPatients who have received prior treatment with a P13K inhibitor or RAD001 (if discontinued for toxicity)Xx_NEWLINE_xXPatients who have received prior treatment with an mammalian target of rapamycin (mTOR) inhibitor (e.g., sirolimus, temsirolimus, everolimus)Xx_NEWLINE_xXParticipants should not have taken valproic acid or another histone deacetylase inhibitor for at least 2 weeks prior to study enrollmentXx_NEWLINE_xXNo prior systemic chemotherapy for metastatic disease; one prior therapeutic regimen with a non-tyrosine kinase inhibitor, such as an mammalian target of rapamycin (mtor) inhibitor is allowed; patients who were randomized to placebo on an adjuvant study are eligibleXx_NEWLINE_xXPatient had prior treatment with an histone deacetylase (HDAC) inhibitor (e.g., romidepsin [Depsipeptide], NSC-630176, MS 275, LAQ-824, belinostat [PXD-101], LBH589, MGCD0103, CRA024781, etc); patients who have received compounds with HDAC inhibitor-like activity, such as valproic acid, as anti-tumor therapy should not enroll in this study; patients who have received such compounds for other indications, e.g. valproic acid for epilepsy, may enroll after a 30-day washout periodXx_NEWLINE_xXPrevious treatment with or inability to receive BL22 or HA22 recombinant immunotoxin; patients must have had at least 2 prior systemic therapies, including 2 courses of a purine nucleoside analog (PNA), or 1 course of either rituximab or B-RAF proto-oncogene, serine/threonine kinase gene (BRAF) inhibitor following a single prior course of PNAXx_NEWLINE_xXAny previous Janus kinase 2 gene (JAK2) inhibitor treatment prior to study enrollment, with the exception of ruxolitinibXx_NEWLINE_xXHypersensitivity to Janus kinase (JAK) inhibitorXx_NEWLINE_xXPatients must not have received an aromatase inhibitor (AI) or a selective estrogen receptor modulator (SERM) such as tamoxifen or raloxifene within 5 years prior to registrationXx_NEWLINE_xXSubjects with B-Raf V600 (BRAFV600) mutated tumors who have received prior BRAF inhibitor therapy either alone or in combination with MEK inhibitor as their only prior systemic therapy are eligible.Xx_NEWLINE_xXConcomitant oral mTOR inhibitor treatmentXx_NEWLINE_xXHas had prior exposure to tazemetostat or other inhibitor(s) of EZH2Xx_NEWLINE_xXReceived previous therapy with capecitabine, neratinib, lapatinib, or any other HER2 directed tyrosine kinase inhibitor.Xx_NEWLINE_xXPrior treatment with a FLT3 targeted therapy including sorafenib or investigational FLT3 inhibitors (not including the multi-kinase inhibitor, midostaurin).Xx_NEWLINE_xXProgressive disease with radiographic evidence of disease progression per investigator assessment during therapy with an EGFR tyrosine kinase inhibitor in the metastatic setting; patients may continue EGFR inhibitor therapy throughout the screening period until the day prior to nab-paclitaxel treatment initiationXx_NEWLINE_xXDocumented progressive disease during or after JAK inhibitor therapyXx_NEWLINE_xXPatients must not have had prior exposure to any agent with a PARP inhibitor (e.g., veliparib, olaparib, rucaparib, niraparib, talazoparib [BMN 673]) as its primary pharmacologyXx_NEWLINE_xXPrevious treatment with checkpoint inhibitor drugsXx_NEWLINE_xXPatient has had prior treatment with a known PARP inhibitorXx_NEWLINE_xXPrior treatment with inhibitor of MET or HGFXx_NEWLINE_xXPrior exposure to EGFR tyrosine kinase inhibitorsXx_NEWLINE_xXPrior treatment with CDK4/6 inhibitorXx_NEWLINE_xXReceived Janus kinase inhibitor therapy after allo-HSCT for any indication. Treatment with a JAK inhibitor before allo-HSCT is permitted.Xx_NEWLINE_xXPrior treatment with any selective inhibitor (e.g., AZD4547, BGJ398, JNJ-42756493, BAY1179470) of the FGF-FGFR pathwayXx_NEWLINE_xXTreatment naïve (ie, no prior chemotherapy in the metastatic disease setting and no prior ALK inhibitor therapy allowed).Xx_NEWLINE_xXDisease progression after 1 prior ALK inhibitor therapy other than crizotinib. Patients may have had any number of prior chemotherapy regimens in any disease setting.Xx_NEWLINE_xXTreatment naïve (ie, no prior chemotherapy in the metastatic disease setting and no prior ROS inhibitor therapy).Xx_NEWLINE_xXAny number of prior therapies (ie, chemotherapy and/or ROS inhibitor therapies).Xx_NEWLINE_xXPrior treatment with a PARP inhibitor (not including iniparib)Xx_NEWLINE_xXPart 2: Progression of disease following one VEGF pathway inhibitor for RCC (e.g. sunitinib, pazopanib, sorafenib, bevacizumab, tivozanib, or cabozantinib) inclusive of adjuvant therapy if there was documented disease progression during treatment. Patients may have received one additional line of an approved mTOR kinase inhibitor (e.g. everolimus, temsirolimus). Prior exposure to investigational and/or approved anticancer immune therapies is permitted.Xx_NEWLINE_xXreceived prior treatment with any cyclin-dependent kinase (CDK) 4 and CDK 6 inhibitorXx_NEWLINE_xXPrior treatment with a known poly(ADP-ribose) polymerase (PARP) inhibitorXx_NEWLINE_xXPatients with Philadelphia chromosome positive (Ph+) ALL are eligible if they are intolerant to or have failed 2 lines of tyrosine kinase inhibitor therapy (TKI), or if TKI therapy is contraindicated ORXx_NEWLINE_xXPrior treatment with a PI3K or protein kinase B (AKT) inhibitor; patients previously treated with an mechanistic target of rapamycin (mTOR) inhibitor are eligibleXx_NEWLINE_xXReceived at least 2 prior lines of therapy for MM including an immunomodulatory drug and a proteasome inhibitor.Xx_NEWLINE_xXPRIOR/CONCURRENT THERAPY CRITERIA: Patients must not have received prior docetaxel; patients must not have received therapy with a drug known to be either a mitogen-activated protein kinase (MEK) inhibitor or a phosphatidylinositol 3 kinase (PI3K)/v-akt murine thymoma viral oncogene homolog 1 (AKT)/mammalian target of rapamycin (mTOR) pathway inhibitorXx_NEWLINE_xXPrior anti-myeloma treatments must have included an immunomodulatory drug (IMiD) AND proteasome inhibitor alone or in combination and participant must have failed therapy with an IMiD OR proteasome inhibitorXx_NEWLINE_xXPrior exposure to ibrutinib or to a BCR inhibitor or a BCL-2 inhibitor.Xx_NEWLINE_xXRequires treatment with a strong CYP3A inhibitor/inducer.Xx_NEWLINE_xXMelanoma\r\n* Unresectable or metastatic disease progression following a B-Raf proto-oncogene, serine/threonine kinase (BRAF) inhibitor if BRAF V600 positive\r\n* Note: prior therapy with ipilimumab not requiredXx_NEWLINE_xXFor Dose escalation cohort - progressive disease on at least one prior EGFR-tyrosine kinase inhibitor (TKI) (previous treatment with 3rd generation EGFR-TKI including AZD9291 allowed for dose escalation)Xx_NEWLINE_xXSubject has previously been treated with a HDAC inhibitor, PD-1 inhibitor, PD-L1 inhibitor, PD-L2 inhibitor, CTLA-4 inhibitor, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathwaysXx_NEWLINE_xXPrior treatment with any VEGFR tyrosine kinase inhibitorXx_NEWLINE_xXParticipant must not have been previously treated with proteasome inhibitors. (The sponsor reserves the right to open the study to proteasome inhibitor-exposed participants in the future, at some time point after the first interim analysis (IA). In that case, the participant may not be refractory to proteasome inhibitor therapy.)Xx_NEWLINE_xXPrior treatment with any CDK4/6 inhibitor.Xx_NEWLINE_xXPrior systemic regimens must include previously approved therapies, including a platinum-containing chemotherapy regimen; a tyrosine kinase inhibitor for tumors with driver mutations; and checkpoint inhibitors where approved.Xx_NEWLINE_xXPrior receipt of an IDO inhibitor.Xx_NEWLINE_xXPrior receipt of a BET inhibitor (Treatment Group B only).Xx_NEWLINE_xXPrior receipt of an LSD1 inhibitor including INCB059872 (Treatment Group C only).Xx_NEWLINE_xXPrior treatment with lenvatinib or any tyrosine kinase inhibitor (TKI) - (except for combination therapy of radiation and reduced dose of TKI given for the purpose of radiosensitization).Xx_NEWLINE_xXPatients with Philadelphia chromosome positive (Ph+) ALL are eligible if they are intolerant to or have failed 2 lines of tyrosine kinase inhibitor therapy (TKI), or if TKI therapy is contraindicated OR.Xx_NEWLINE_xXHave discontinued previous experimental therapies and checkpoint inhibitor antibodies at least 28 days prior to the Randomization VisitXx_NEWLINE_xXPart 2, Cohort 3: Histologically and/or cytologically confirmed diagnosis of breast cancer with hormone receptor-positive status (ER and/or PgR positive) and HER2-negative status with prior exposure to tamoxifen and/or an aromatase inhibitor and/or an aromatase inhibitor plus palbociclib. Prior treatment with tamoxifen in the neoadjuvant setting is allowed but must have been discontinued for at least 1 year prior to the first dose.Xx_NEWLINE_xXImmediate prior therapy with a PAM pathway inhibitor (i.e., the subject is excluded if the last treatment regimen, prior to MSC2363318A, was a PAM pathway inhibitor, or if the last PAM pathway inhibitor that the subject was treated with occured less than 2 months prior to Day 1 of trial drug treatment).Xx_NEWLINE_xXChemotherapy: non-cytotoxic (e.g., small molecule inhibitor) At least 14 daysXx_NEWLINE_xXHave previously received treatment with any cyclin-dependent kinase (CDK) 4 and 6 inhibitor or phosphatidylinositol 3-kinase (PI3K) and/or mammalian target of rapamycin (mTOR) inhibitor or have a known hypersensitivity to any component of the investigational products in this study.Xx_NEWLINE_xXParticipant has received prior therapy with a Poly-(ADP-ribose)-Polymerase (PARP) inhibitor.Xx_NEWLINE_xXPatients must not have received prior PARP inhibitor therapy including, but not limited to ABT-888, olaparib, rucaparib, and talazoparib (BMN637)Xx_NEWLINE_xXPrevious treatment with another Bruton's Tyrosine Kinase (BTK) -inhibitor.Xx_NEWLINE_xXPrior exposure to a BCL-2 inhibitor (eg, venetoclax/ABT-199)Xx_NEWLINE_xXPrior therapy for ovarian or uterine cancer with ribociclib or an aromatase inhibitor (letrozole, anastrozole or exemestane)Xx_NEWLINE_xXTreatment with erlotinib must be discontinued at least 3 days prior to first dose of tesevatinib and treatment with afatinib or other tyrosine kinase inhibitor must be discontinued at least 3 days prior to first dose of tesevatinibXx_NEWLINE_xXPrevious therapy with GS-1101 (CAL-101, Idelalisib), IPI-145 (Duvelisib), TGR-1202 or any drug that specifically inhibits PI3K/ mTOR (including temsirolimus, everolimus), AKT or BTK Inhibitor (including Ibrutinib) in last 6 monthsXx_NEWLINE_xXPatient must have been previously treated with an aromatase inhibitor (either letrozole, anastrozole or exemestane) either in the adjuvant or metastatic setting, and have one of the following types of primary or secondary endocrine resistant disease\r\n* Primary clinical resistance is defined as one of the following:\r\n** Recurrence within the first 2 years of adjuvant endocrine therapy while on aromatase inhibitor therapy\r\n** Progression within first 6 months of initiating first-line endocrine therapy (either aromatase inhibitor or fulvestrant containing regimen) for the treatment of metastatic breast cancer \r\n* Secondary clinical resistance is defined as one of the following:\r\n** Recurrence after year 2 while receiving adjuvant aromatase inhibitor therapy, or within 12 months of completing adjuvant aromatase inhibitor therapy\r\n** Progression occurring 6 or more months after initiating the first endocrine therapy for metastatic disease (either fulvestrant or aromatase inhibitor containing regimen)Xx_NEWLINE_xXAny previous treatment with a Polyadenosine 5'diphosphoribose polymerisation (PARP) inhibitor, including olaparib.Xx_NEWLINE_xXHas had prior exposure to tazemetostat or other inhibitor(s) of enhancer of zeste homolog 2 (EZH2)Xx_NEWLINE_xXPrior treatment with: second generation androgen receptor (AR) inhibitors, other investigational AR inhibitors, or CYP17 enzyme inhibitor.Xx_NEWLINE_xXReceipt of prior mitogen-activated protein kinase inhibitor pathway agents including mitogen-activated protein kinase inhibitor and BRAF kinase inhibitorXx_NEWLINE_xXAny prior or concomitant use of another JAK inhibitorXx_NEWLINE_xXGroup A: Prior treatment with a selective phosphatidylinositol 3-kinase (PI3K) ? inhibitor (eg, idelalisib), a pan-PI3K inhibitor, or a BTK inhibitor (eg, ibrutinib).Xx_NEWLINE_xXGroup B: Prior treatment with a selective PI3K? inhibitor (eg, idelalisib) or a pan PI3K inhibitor.Xx_NEWLINE_xXNon-cytotoxic chemotherapy (e.g., small molecule inhibitor); at least 14 days since last doseXx_NEWLINE_xXHas had prior exposure to tazemetostat or other inhibitor(s) of enhancer of zeste homologue-2 (EZH2)Xx_NEWLINE_xXPrior therapy with obinutuzumab and/or chlorambucil or a PI3K delta inhibitorXx_NEWLINE_xXPrior therapy with histone deacetylase (HDAC) inhibitor.Xx_NEWLINE_xXPatients who have received prior treatment with a mutant-specific IDH1 inhibitor (with the exception of glioma patients)Xx_NEWLINE_xXPrior treatment with a phosphatidylinositol 3-kinase (PI3K) inhibitor, mammalian target of rapamycin (mTOR) inhibitor (e.g. everolimus), or protein kinase B (AKT) inhibitorXx_NEWLINE_xXNo Bruton’s tyrosine kinase inhibitor at any point prior to enrollmentXx_NEWLINE_xXPrior exposure to a Bruton's tyrosine kinase (BTK) inhibitorXx_NEWLINE_xXPrior tyrosine kinase inhibitor therapy or palliative radiation within 7 days of first dose of study medicationXx_NEWLINE_xXPrevious treatment with carboplatin, paclitaxel, doxorubicin, cyclophosphamide and a Poly-(ADP-ribose)-Polymerase (PARP) inhibitor.Xx_NEWLINE_xXPatients must be willing to be off EGFR-tyrosine-kinase inhibitor (TKI) therapy for a minimum of one week; (in expansion cohort A patients on erlotinib do not have to discontinue treatment)Xx_NEWLINE_xXPrior treatment with a MET inhibitor or HGF targeting agentXx_NEWLINE_xXGroup 2 - Patients must have disease progression while on or within one month after CDK4/6 inhibitor based therapyXx_NEWLINE_xXHistologically confirmed advanced or metastatic renal cell carcinoma with a clear cell component that has progressed by investigator assessment following treatment with one and only one multi-targeted tyrosine kinase inhibitor (TKI) other than axitinib that targets the VEGF receptor (VEGFR) (e.g., sunitinib, pazopanib, sorafenib, tivozanib, cabozantinib). One prior immunotherapy (interleukin-2 or interferon-alpha or immune checkpoint inhibitor or tumor vaccine) and one prior mTOR inhibitor treatment are allowed.Xx_NEWLINE_xXPatients should not have taken valproic acid or another histone deacetylase inhibitor for at least 2 weeks prior to enrollmentXx_NEWLINE_xXPrior therapy with an IDO1 or arginase 1 inhibitor.Xx_NEWLINE_xXUse of 5-alpha reductase inhibitor within the 3 months prior to dosing.Xx_NEWLINE_xXSubjects who received prior therapy with checkpoint inhibitorXx_NEWLINE_xXPatients must not have previously received a histone deacetylase (HDAC) inhibitor in a clinical trial setting (entinostat, romidepsin, belinostat, panobinostat, vorinostat)Xx_NEWLINE_xXGroup 1: BRAFV600 positive metastatic or recurrent melanoma after failure of prior treatment with standard therapy such as a checkpoint inhibitor and an approved B-RAF inhibitor (vemurafenib or dabrafenib)Xx_NEWLINE_xXTreatment with a complement inhibitor at any time.Xx_NEWLINE_xXPrior treatment with bortezomib or other proteasome inhibitor is allowed, provided ALL of the following criteria are met: Disease is NOT refractory to any proteasome inhibitor, defined as no disease progression (i.e., PD, per IMWG or European Society for Blood and Marrow Transplantation [EBMT] criteria) while receiving proteasome inhibitor therapy or within 60 days after the last dose, AND best response achieved with any proteasome inhibitor therapy (alone or in combination) was at least a PR, AND participant did not discontinue any proteasome inhibitor due to intolerance or greater than or equal to Grade 3 related toxicity.Xx_NEWLINE_xXParticipant is refractory to any proteasome inhibitor, defined as progression on or within 60 days of the last dose of a proteasome inhibitor-containing regimen.Xx_NEWLINE_xXParticipant has had prior treatment with proteasome inhibitor within 60 days prior to first dose of study drug.Xx_NEWLINE_xXArm B only: ibrutinib or other Bruton's tyrosine kinase (BTK) inhibitor;Xx_NEWLINE_xXPreviously received JAK inhibitor therapy for any indication.Xx_NEWLINE_xXSubjects must have received at least 3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory (IMID) agent OR were double-refractory to both an IMID and a PI. Refractory is defined as progressing on-treatment or within 60 days of the last dose.Xx_NEWLINE_xXPatients who have previously received ibrutinib or another inhibitor of Bruton's tyrosine kinase (BTK)Xx_NEWLINE_xXHave received prior treatment with any cyclin dependent kinase (CDK) 4 and 6 inhibitor or participated in a clinical trial with a CDK 4 and 6 inhibitor and the treatment administered is not known.Xx_NEWLINE_xXPrevious treatment with an investigational or marketed agent known to inhibit EGFR (e.g. EGF monoclonal antibody therapy, dual TKI inhibitor).Xx_NEWLINE_xXPrevious treatment with an investigational or marketed agent known to inhibit EGFR (e.g. EGF monoclonal antibody therapy, dual TKI inhibitor).Xx_NEWLINE_xXPrevious treatment with a c-MET inhibitor or HGF-targeting therapy.Xx_NEWLINE_xXPrior treatment with any CDK 4/6 inhibitorXx_NEWLINE_xXPatient who has received a prior CDK4/6 inhibitorXx_NEWLINE_xXHave received prior treatment with any cyclin-dependent kinase (CDK) 4/6 inhibitor (or participated in any CDK4/6 inhibitor clinical trial for which treatment assignment is still blinded)Xx_NEWLINE_xXPatients who have previously received everolimus, any another mTOR inhibitor or any agent targeting the PI3K/AKT/mTOR pathway.Xx_NEWLINE_xXPatients must not have been treated with any of the following prior to Step 1 Randomization:\r\n* Cetuximab, panitumumab, or any other monoclonal antibody against EGFR or inhibitor of EGFR\r\n* BRAF inhibitor including, but not limited to, vemurafenib or dabrafenib; regorafenib is not considered a BRAF inhibitor for the purpose of determining trial eligibility\r\n* Mitogen-activated protein/extracellular signal–regulated kinase (MEK) inhibitor including, but not limited to, trametinib or selumetinibXx_NEWLINE_xXHistory of hemoptysis (>= 1/2 teaspoon of bright red blood per episode) or other significant spontaneous bleeding event within 1 month prior to day 1 of study drug or at any time on a prior VEGF inhibitorXx_NEWLINE_xXConcomitant treatment with strong inhibitor of P-gp.Xx_NEWLINE_xXFor Part D (abemaciclib + LY3023414): Any subtype. The participant must have received at least two, but not more than three prior therapies for advanced/metastatic NSCLC. The participant must not have received prior treatment with any phosphoinositide 3-kinase (PI3K) or mammalian target of rapamycin (mTOR) inhibitor.Xx_NEWLINE_xXPrior enrollment into a clinical trial of a PARP inhibitorXx_NEWLINE_xXPrior therapy with an anti-cytotoxic T-lymphocyte antigen 4 (CTLA4) antibody or an histone deacetylases (HDAC) inhibitorXx_NEWLINE_xXPrior therapy with ibrutinib or other kinase inhibitors that target Bruton’s tyrosine kinase (BTK); patients who previously received therapy with the phosphoinositide-3 kinase (PI3K) delta inhibitor idelalisib (Zydelig) are allowed to be enrolledXx_NEWLINE_xXPrior use of a JAK1 or JAK2 inhibitorXx_NEWLINE_xXPrior treatment with any PARP inhibitor, including rucaparib. Patients who received prior iniparib are eligible.Xx_NEWLINE_xXPrior treatment with any CDK inhibitor, fulvestrant, everolimus, or agent that inhibits the PI3K-mTOR pathwayXx_NEWLINE_xXPrior treatment with a PARP inhibitorXx_NEWLINE_xXPrior treatment with any CDK 4/6 inhibitor.Xx_NEWLINE_xXPrior exposure to a BTK inhibitorXx_NEWLINE_xXUse of a strong CYP3A4 inducer or inhibitor, or strong CYP2C8 inducer or inhibitor within 3 elimination half-lives of the inhibitor or inducer prior to first dose of study treatmentXx_NEWLINE_xXPrior treatment with any PARP inhibitorXx_NEWLINE_xXDisease that progressed during treatment or within 1 month after the end of treatment with prior tamoxifen, AI, or cyclin-dependent kinase (CDK) 4/6 inhibitor plus letrozole, for advanced/metastatic disease.Xx_NEWLINE_xXIf the patient has disease with a BRAF mutation, s/he must have received treatment with appropriate BRAF/MEK inhibitor as single agent therapy or in combination, or be intolerant to, or refuse such treatment.Xx_NEWLINE_xXPrevious treatment with PARP inhibitor. For this study, BSI-201 (iniparib) is not considered as PARPiXx_NEWLINE_xXPrior or concurrent therapy with a Janus kinase inhibitor or Bruton's tyrosine kinase inhibitorXx_NEWLINE_xXPatients must have symptomatic or radiographic progression during or after treatment with a PD-(L)1 inhibitor administered either as monotherapy or in combination.Xx_NEWLINE_xXPrior BRAF or MEK inhibitor treatment is not required. However, for patients with known BRAF status:Xx_NEWLINE_xXPrevious treatment with either a PD-1 inhibitor (for patients enrolling on the IMO-2125 + pembrolizumab combination) or CTLA-4 inhibitor (for patients enrolling on the IMO-2125 + ipilimumab combination if applicable) should not have been accompanied by DLT for which permanent discontinuation is recommended (per USPI).Xx_NEWLINE_xXPatients with a history of Grade ?2 gastrointestinal symptoms (e.g., diarrhea, colitis) during prior checkpoint inhibitor treatment should be discussed with the Idera Medical Monitor during the Screening Period before starting study treatment.Xx_NEWLINE_xXSubjects with Ph+ disease are eligible if they are intolerant to tyrosine kinase inhibitor (TKI) therapy, or if they have relapsed/refractory disease despite treatment with at least 2 different TKIsXx_NEWLINE_xXPatients in Phase 2 expansion cohort A will have experienced disease progression with 1 systemic treatment containing a checkpoint inhibitor. Any prior liver directed therapy is acceptable.Xx_NEWLINE_xXPatients who have prior therapy with everolimus or any other mammalian target of rapamycin (mTOR) inhibitorXx_NEWLINE_xXPrior receipt of a selective FGFR inhibitorXx_NEWLINE_xXHave received at least 3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD) in any order during the course of treatment for multiple myeloma or have disease that is refractory to both a PI and an IMiDXx_NEWLINE_xXPatients who have received prior treatment with an mTOR inhibitor (e.g., sirolimus, temsirolimus, everolimus).Xx_NEWLINE_xXEGFR, ALK and ROS biomarker positive tumors are eligible as long as the patient has received at least one standard oral, molecular inhibitor therapy in addition to standard platinum doublet chemotherapy. More than one molecular inhibitor is allowed such as a first generation EGFR inhibitor followed by a next generation EGFR inhibitor when T790 mutation develops. Prior molecular therapy for biomarker positive tumors such as (but not limited to) MET, RET and BRAF allowed but not required.Xx_NEWLINE_xXPatients requiring treatment with a RANKL inhibitor (e.g. denosumab) who cannot discontinue it before treatment with atezolizumabXx_NEWLINE_xXPrior BRAF or MEK inhibitor therapyXx_NEWLINE_xXPatients must be resistant to, intolerant of, or ineligible for Janus kinase (JAK)2 inhibitor therapy, or have refused such therapyXx_NEWLINE_xXPrior chemotherapy or tyrosine kinase inhibitor (TKI) treatment, aside from dasatinib, must be >= 7 days before first investigational agent doseXx_NEWLINE_xXHave T790M-positive status using a test validated and performed locally after disease progression on EGFR tyrosine kinase inhibitor (TKI) treatment.Xx_NEWLINE_xXPrior therapy with a histone deacetylase (HDAC) inhibitorXx_NEWLINE_xXPatients previously treated with ibrutinib or PI3K inhibitorXx_NEWLINE_xXHave received treatment with a prior cyclin-dependent kinase (CDK4) and CDK 6 inhibitor.Xx_NEWLINE_xXHas been previously treated with a Bromodomain and Extra-Terminal (BET) inhibitorXx_NEWLINE_xXPrior therapy for SMM with a proteasome inhibitorXx_NEWLINE_xXHave a histologically proven BCC in which curative resection is unlikely without significant morbidity, or have nodal or distantly metastatic disease which has progressed on smoothened inhibitor monotherapy (ARM 1) or has undergone partial response or stable disease on smoothened inhibitor monotherapy (ARM 2); individuals who are intolerant or have medical contra-indication to smoothened inhibitor may be enrolled into ARM 1Xx_NEWLINE_xXPrior mTOR inhibitor therapy within 4 weeks prior to first dose of study drug.Xx_NEWLINE_xXPrior treatment with a CDK4/6 inhibitor and/or bazedoxifeneXx_NEWLINE_xXone additional cytotoxic regimen and/or PARP inhibitor for management of recurrent or persistent disease.Xx_NEWLINE_xXHistory of a prior significant toxicity, other than thrombocytopenia, from another Bcl-2 family protein inhibitorXx_NEWLINE_xXKnown cysteine-481 Bruton's tyrosine kinase (BTK) mutation or CLL refractory to or progressed during ibrutinib or other cysteine (Cys)-481 binding BTK inhibitor treatmentXx_NEWLINE_xXHistory of prior janus kinase (JAK) or STAT3 inhibitor treatmentXx_NEWLINE_xXPrior exposure to a proteasome inhibitor (PI)Xx_NEWLINE_xXPrevious treatment with any aminopeptidase inhibitorXx_NEWLINE_xXHistologically or cytologically confirmed metastatic or unresectable locally advanced NSCLC with known sensitive EGFR mutations; patients with mutations in T790M are eligible if they have progressed after treatment with a third generation EGFR tyrosine kinase inhibitor (osimertinib), but otherwise patients must have EGFR T790M negative or unknown status; patients previously treated with third generation EGFR tyrosine kinase inhibitor must have achieved a treatment benefit of at least 4 monthsXx_NEWLINE_xXPrior therapy with a proteasome inhibitor if discontinued due to toxicityXx_NEWLINE_xXParticipants with concurrent use of calcineurin-inhibitor plus sirolimus (either agent alone is acceptable)Xx_NEWLINE_xXPatients may not have received previous therapy with a MET inhibitorXx_NEWLINE_xXThe patient has received prior treatment with a PI3K inhibitor, AKT inhibitor, or mechanistic target of rapamycin (serine/threonine kinase) (mTOR) inhibitor (e.g. rapamycin, MK2206, perifosine, etc.)Xx_NEWLINE_xXGroup A: prior therapy with any ALK inhibitor is not permitted.Xx_NEWLINE_xXGroup B: progression following any ALK inhibitor(s) other than ceritinib is required and the last dose of the ALK inhibitor must be no more than 60 days prior to the first dose of study drug. Prior ceritinib is not permitted.Xx_NEWLINE_xXPrior treatment with a PARP inhibitorXx_NEWLINE_xXPrior therapy with everolimus or an aromatase inhibitorXx_NEWLINE_xXPrior treatment with an HGF/cMet inhibitor such as rilotumumab, crizotinib, MetMAb (onartuzumab), or ARQ197 (tivantinib)Xx_NEWLINE_xXPrior cytotoxic therapy and immunotherapy are allowed; for the dose escalation, prior targeted therapy with a MEK inhibitor, protein kinase C inhibitor, Akt, or mTOR inhibitor are allowed; for the dose expansion cohort, no prior MEK, protein kinase C (PKC), Akt, or mTOR inhibitors are allowed, and registration is limited to 10 total patients; local therapies such as radiofrequency ablation or cryotherapy for metastatic disease are permitted but must have been performed at least 21 days prior to initiation of study therapy; lesions treated with local or regional modalities such as radiofrequency ablation, or cryotherapy may not be used as target lesions unless they demonstrate growth over a minimum of 3 months on subsequent imaging studiesXx_NEWLINE_xXPrior treatment with 1 or more tyrosine kinase inhibitor drugs (imatinib, dasatinib and/or nilotinib) for Philadelphia Chromosome positive Chronic Myeloid Leukemia (CML).Xx_NEWLINE_xXPatients who have received prior treatment with a phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (P13K) inhibitorXx_NEWLINE_xXAny prior treatment with an aurora kinase inhibitor (either an aurora A kinase or pan-aurora kinase inhibitor)Xx_NEWLINE_xXPrior treatment with Trastuzumab in combination with Lapatinib or prior treatment with an irreversible inhibitor of the intracellular domain of the HER2 receptor such as neratinibXx_NEWLINE_xXPatients may have unlimited prior chemotherapeutic regimens for management of recurrent locally advanced endometrial carcinoma, recurrent ovarian carcinoma, or metastatic triple negative breast cancer; treatment as frontline therapy for metastatic disease is acceptable; patients who have received prior poly (adenosine diphosphate [ADP]-ribose) polymerase 1 (PARP) inhibitors, MTOR inhibitors, and/or AKT inhibitors are allowed to participate; patients may have progressed on prior PARP inhibitor, MTOR inhibitor, or AKT inhibitor but they may not have discontinued drug for toxicityXx_NEWLINE_xXHistory of treatment with a tyrosine kinase inhibitor (eg, imatinib), purine analogs or other cancer chemotherapy in the 4 weeks prior to starting study drug.Xx_NEWLINE_xXPrior or current treatment with a cMet inhibitorXx_NEWLINE_xXPrior treatment with a mitogen-activated protein kinase kinase (MEK) inhibitor of any kindXx_NEWLINE_xXPatients who have received or been treated with an tumor necrosis factor-alpha inhibitor such as adalimumab (Humira) within four weeks of starting on studyXx_NEWLINE_xXPrior treatment with any Hsp90 inhibitor.Xx_NEWLINE_xXPrior treatment with a PARP inhibitorXx_NEWLINE_xXAt least one prior therapy; prior autologous or allogeneic stem cell transplant is allowed; patients may not be on chronic immunosuppressive therapy for graft-versus-host disease (GVHD); patients who have received prior treatment with a pan-selective PI3K inhibitor are not eligible; however, prior therapy with a selective PI3K inhibitor, Bruton‘s tyrosine kinase inhibitor, or other B-cell receptor targeting agents is allowedXx_NEWLINE_xXNo prior chemotherapy, Bruton's tyrosine kinase (BTK) inhibitor therapy, or monoclonal anti-body therapy for treatment of CLL or SLLXx_NEWLINE_xXPrior therapy with any cyclin-dependent kinase 4/6 (CDK4/6) inhibitorXx_NEWLINE_xXNo prior MET inhibitor is allowedXx_NEWLINE_xXHistologically proven advanced MPM, advanced peritoneal mesothelioma (for dose escalation cohort only) or non-squamous NSCLC (stage IIIB/IV) who have not been treated with prior chemotherapy or immunotherapy, except that NSCLC subjects with EGFR mutant or ALK positive must have had an EGFR tyrosine kinase inhibitor (TKI) or ALK inhibitor and progressed or been shown to be intolerant of therapy prior to enrolling in this trial, if such ALK inhibitor and EGFR targeted therapy are approved and available in the country in which patients are being enrolled OR Histologically proven metastatic uveal melanoma who have not been treated with prior chemotherapy (MTD cohort only), OR Histologically proven HCC who have failed (PD and/or side effects-been intolerant of) treatment with sorafenib. Failure is defined as having progressed radiographically on, or been intolerant to prior systemic therapy. Intolerance is defined as discontinuation due to an AE(s) on prior systemic therapy that was unacceptable to the treating physician and / or patient, with or without dose interruption and modification. Failure requires at least 14 days of treatment with sorafenib, except for a subject that has had a severe allergic reaction to sorafenib at any time, even less than 14 days of treatment with sorafenib and thus it would be imprudent to re-challenge them with that agent. Cirrhotic status of Child-Pugh grade A-B7 must be present. Child-Pugh status should be determined based on clinical findings and laboratory data during the screening period (Appendix E). Subjects on anti-coagulants are to receive 1 point for their INR status, as they are presumed to have a <1.7 baseline PT/INR.\, OR Histologically proven high-grade glioma who have failed (PD and/or side effects) treatment with radiotherapy ± temozolomide, OR Sarcomatoid cancer of any line.Xx_NEWLINE_xXRelapsed after, or refractory to, prior BTK inhibitor therapy.Xx_NEWLINE_xXCOHORT A: Prior use of a 5 alpha reductase inhibitor is allowed (no limit on duration of use); however a two week washout is requiredXx_NEWLINE_xXCOHORT A: A history of prior treatment with ipilimumab or prior CD137 agonist or cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitor or agonistXx_NEWLINE_xXCOHORT B: Prior use of a 5 alpha reductase inhibitor is allowed (no limit on duration of use); however a two week washout is requiredXx_NEWLINE_xXCOHORT B: A history of prior treatment with ipilimumab or prior CD137 agonist or CTLA-4 inhibitor or agonistXx_NEWLINE_xXPrior treatment with a topoisomerase I inhibitor (i.e. irinotecan, topotecan)Xx_NEWLINE_xXTyrosine kinase inhibitor within 7 days of randomizationXx_NEWLINE_xXPrevious treatment with a PI3K inhibitor or BTK inhibitorXx_NEWLINE_xXPrior treatment with PARP inhibitor.Xx_NEWLINE_xXPrior therapy with HDAC inhibitorXx_NEWLINE_xXHistory of prior significant toxicity from another mitogen-activated protein kinase (MEK) pathway inhibitor requiring discontinuation of treatmentXx_NEWLINE_xXUse of a strong CYP3A4 inhibitor within three elimination half-lives of the inhibitor prior to the start of study treatment.Xx_NEWLINE_xXUse of a strong CYP2C8 inducer or inhibitor within three elimination half-lives of the inducer or inhibitor prior to the start of study treatment.Xx_NEWLINE_xXAny previous exposure to a CYP17 (17?-hydroxylase/C17,20-lyase) inhibitor;Xx_NEWLINE_xXAny previous treatment with a PARP inhibitor, including olaparib.Xx_NEWLINE_xXPatients must not have received prior therapy with a tyrosine kinase inhibitor (TKI)Xx_NEWLINE_xXParticipants who have a history of prior MM treatment with panobinostat, or an alternative histone deacetylase (HDAC)-inhibitorXx_NEWLINE_xXPatient who received any CDK4/6 inhibitor.Xx_NEWLINE_xXReceipt of PARP inhibitor prior to RT.Xx_NEWLINE_xXAny previous treatment with PARP inhibitor, including olaparib, for the treatment of small cell lung cancer.Xx_NEWLINE_xXConcurrently receiving treatment with calcineurin-inhibitor plus sirolimus (either agent alone is acceptable).Xx_NEWLINE_xXSubjects (other than those in the ibrutinib + JCAR017 combination therapy arm) must have received and failed Bruton tyrosine kinase inhibitor (BTKi) treatment or have been deemed ineligible for BTKi therapy.Xx_NEWLINE_xXPrior treatment with a PARP inhibitor.Xx_NEWLINE_xXCurrent or anticipated use of a P glycoprotein (P gp) inhibitor (eg, dronedarone, quinidine, ranolazine, itraconazole, ketoconazole), strong P gp inducer (eg, rifampin, ritonavir, tipranavir), or strong inhibitor of breast cancer resistance protein (BCRP) (eg, elacridar [GF120918]).Xx_NEWLINE_xXPatients who requires treatment with a potent cytochrome P450 (CYP) 3A inhibitor or inducerXx_NEWLINE_xXHave received prior therapy with an immunomodulatory agent, a proteosome inhibitor, and glucocorticoidsXx_NEWLINE_xXNo prior enzalutamide, abiraterone, or other novel antiandrogen or androgen synthesis inhibitorXx_NEWLINE_xXPrior treatment with a Mitogen-Activated protein Kinase (MEK) inhibitor or any docetaxel-containing regimen (prior treatment with paclitaxel is acceptable).Xx_NEWLINE_xXIn the Phase 2 portion of the trial only, subjects who have previously received treatment with an inhibitor of IDH.Xx_NEWLINE_xXPrior therapy with a BRAF inhibitor and/or a MEK- inhibitorXx_NEWLINE_xXPatients with a history of clinical benefit from prior RAF inhibitor therapy, as judged by the investigator, will be allowedXx_NEWLINE_xXPatients progressing on a prior BRAF inhibitor-based therapy will be eligible, as are patients nave to BRAF inhibitor therapy; resistance to BRAF inhibitor-based therapy will be defined as progressive disease by RECIST 1.1 criteria while receiving therapy with a BRAF inhibitor (vemurafenib or dabrafenib, alone or in combination with a mitogen-activated protein kinase [MEK] inhibitor); this may be innate resistance (patients who never achieved a tumor response while on BRAF inhibitor therapy) or acquired resistance (progression after having a tumor response to BRAF inhibitor therapy); there will not be a period of break between progression on the prior BRAF inhibitor-based therapy and the start of dabrafenib, trametinib and GSK2141795Xx_NEWLINE_xXPatients must have received prior BRAF inhibitor therapy (e.g. dabrafenib, vemurafenib) within 56 days prior to registration; prior trametinib therapy is permitted; patients are not required to interrupt BRAF or MEK inhibitor therapy prior to the initiation of three agent combination therapy on studyXx_NEWLINE_xXincludes an IMiD and proteasome inhibitor as separate lines or a combined line of therapyXx_NEWLINE_xXPrior therapy with Bruton's tyrosine kinase (BTK) inhibitorXx_NEWLINE_xXPrevious treatment with a PI3K inhibitor or BTK inhibitor.Xx_NEWLINE_xXPrior treatment with a topoisomerase-I inhibitor (e.g., topotecan, irinotecan)Xx_NEWLINE_xXPrior PI3K inhibitor or AKT inhibitor (patients previously treated with everolimus are eligible)Xx_NEWLINE_xXNo prior treatment with any HSP90 or histone deacetylase (HDAC) inhibitor compound is allowedXx_NEWLINE_xXPrior therapy with a MEK or BRAF inhibitor.Xx_NEWLINE_xXA history of prior treatment with ipilimumab or prior cluster of differentiation (CD)137 agonist or cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitor or agonistXx_NEWLINE_xXPatients who have received prior treatment with a phosphatidylinositol 3 kinase (P13K) inhibitorXx_NEWLINE_xXMore than two prior lines of cytotoxic chemotherapy in the recurrent/metastatic disease setting (palliative treatment intent)(excluding single agent use of an EGFR inhibitor)Xx_NEWLINE_xXPatients who have received prior treatment with a mammalian target of rapamycin (mTOR) inhibitor (e.g., sirolimus, temsirolimus, everolimus)Xx_NEWLINE_xXPrior therapy with a PI3K inhibitor; prior use of Akt or mammalian target of rapamycin (mTOR) inhibitors are allowedXx_NEWLINE_xXPrior anti-neoplastic treatment with any HSP90 or histone deacetylase (HDAC) inhibitor compoundXx_NEWLINE_xXLast chemotherapy or treatment with another systemic anti-cancer agent must have stopped >= 4 weeks prior to enrollment (or >= 5 half-lives for oral tyrosine-kinase inhibitors); participants with EGFR mutations and ALK gene rearrangement who have not received a tyrosine kinase inhibitor targeting their molecular abnormality (e.g., erlotinib or crizotinib respectively); participants must have recovered (CTCAE =< 1) from acute toxicities of any previous therapy (with the exception of alopecia)Xx_NEWLINE_xXAfter failure of 2nd line treatment with up to two prior lines of therapy, one of which may be an oral tyrosine kinase inhibitor (TKI)Xx_NEWLINE_xXPrevious therapy with a topoisomerase I or II inhibitorXx_NEWLINE_xXPrior therapy with a MEK- inhibitorXx_NEWLINE_xXPrior treatment with CGM097 or other p53/HDM2-interaction inhibitorXx_NEWLINE_xXPrior treatment with a MEK (Mitogen-Activated Protein Kinase) inhibitor or any docetaxel-containing regimen (prior treatment with paclitaxel is acceptable)Xx_NEWLINE_xXPrior treatment with a selective inhibitor of RAF or MEKXx_NEWLINE_xXPrior treatment with a BRAF inhibitor (including but not limited to dabrafenib [GSK2118436], vemurafenib, and LX281/BMS-908662) or a MEK inhibitor (including but not limited to trametinib [GSK1120212], AZD6244, and RDEA119); NOTE: there is no limit to the number of other prior therapies, and patients may be previously untreatedXx_NEWLINE_xXPatients previously treated with potent BRAF inhibitor or MEK inhibitor, including PLX4032/vemurafenib, ARQ 736 for more than 10 days; previous treatment with sorafenib is permittedXx_NEWLINE_xXPatient has received a minimum of 3 years of tyrosine kinase inhibitor treatment (first with imatinib (> 4 weeks) and then switched to nilotinib) since initial diagnosisXx_NEWLINE_xXAny prior therapy with JAK2-tyrosine kinase inhibitor (TKI), hypomethylating agents, histone deacetylase inhibitor (HDACI), mechanistic target of rapamycin inhibitor (mTORi), or immunomodulatory drugs (iMiDs) is allowed as long as it is greater than 3 weeks since last dose of administration and in the case of a JAK2-TKI or HDACI that discontinuation was not due to non-hematologic drug toxicity; an exception to this criteria are patients currently on at least 10mg BID of ruxolitinib for greater than 3 months and who have not shown an optimal response (i.e. without 50% reduction in palpable splenomegaly or 50% reduction in symptom burden); with a reduction of ruxolitinib to 10mg BID these patients may enter onto the study without stopping ruxolitinibXx_NEWLINE_xXPrior therapy with an Mammalian target of rapamycin (mTOR) inhibitorXx_NEWLINE_xXHistory of hormone replacement therapy (estrogens with or without progestin) or an aromatase inhibitor (anastrazole, letrozole, exemestane) within 8 weeks prior to day 1Xx_NEWLINE_xXPatients who have received prior treatment with an mTOR inhibitor or bevacizumabXx_NEWLINE_xXPrior therapy with a PDGFR or c-Met inhibitorXx_NEWLINE_xXA history of prior treatment with ipilimumab or prior cluster of differentiation (CD)137 agonist or CTLA-4 inhibitor or agonistXx_NEWLINE_xXAny prior use of a BRAF or MEK inhibitorXx_NEWLINE_xXPrior treatment with a histone deacetylase (HDAC) inhibitorXx_NEWLINE_xXPrior treatment with an HSP90 inhibitor (e.g. 17-AAG, IPI-504, AUY922, STA-9090 [ganetespib] etc.)Xx_NEWLINE_xXPatients who have received prior treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus)Xx_NEWLINE_xXPrior treatment of breast cancer with temozolomide, a platinum agent, or a Poly (ADP ribose) Polymerase (PARP) inhibitor.Xx_NEWLINE_xXA history of prior treatment with ipilimumab or prior cluster of differentiation (CD)137 agonist or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor or agonistXx_NEWLINE_xXPrior treatment with any PARP inhibitor.Xx_NEWLINE_xXA history of prior treatment with ipilimumab or prior CD137 agonist or cytotoxic T-lymphocyte-associated protein 4 (CTLA4) inhibitor or agonistXx_NEWLINE_xXPrior histone deacetylases (HDAC) inhibitor, deacetylase (DAC) inhibitor, heat shock protein (Hsp)90 inhibitor or valproic acid for the treatment of cancerXx_NEWLINE_xXMF patients must have received prior JAK2 inhibitor therapy, and been found to be intolerant, or refractory/relapsed from prior JAK2 inhibitor therapy, based on investigator assessmentXx_NEWLINE_xXPrior therapy with any proteasome inhibitor other than bortezomib or carfilzomibXx_NEWLINE_xXPrevious treatment with any other tyrosine kinase inhibitorXx_NEWLINE_xXPrevious treatment with a BRAF inhibitor (including but not limited to dabrafenib, vemurafenib, LGX818, and XL281/BMS-908662) or MEK inhibitor (including but not limited to trametinib, AZD6244, and RDEA119) prior to start of study treatment (Note: Prior treatment with dabrafenib is allowed for crossover subjects in Cohort A);Xx_NEWLINE_xXPatients who have received prior treatment with an mTOR inhibitor (e.g., sirolimus, temsirolimus, everolimus); patients who have received prior treatment with Navelbine within prior 12 monthsXx_NEWLINE_xXPrior treatment with a PI3K inhibitorXx_NEWLINE_xXPrior MEK inhibitor therapy is allowedXx_NEWLINE_xXPreviously treated with and developed resistance or intolerance to dasatinib or nilotinib OR developed the T3151 mutation after any tyrosine kinase inhibitor (TKI) therapyXx_NEWLINE_xXEXPANSION COHORT ONLY: Prior mTOR pathway inhibitors or VEGF receptor inhibitor therapyXx_NEWLINE_xXHad any prior treatment with temsirolimus or mTOR inhibitor.Xx_NEWLINE_xXPrevious treatment with any FGFR inhibitor (e.g., ponatinib, dovitinib, nintedanib, AZD4547, NVP-BGJ398, LY2784455, BAY1163877)Xx_NEWLINE_xXa documented NTRK fusion and a clinical history of relapse following a response to a prior TRK inhibitorXx_NEWLINE_xXa documented NTRK fusion unresponsive to a prior TRK inhibitorXx_NEWLINE_xXa documented NTRK fusion and a clinical history of intolerance to a prior TRK inhibitorXx_NEWLINE_xXThe participant has previously received treatment with any CDK4 and CDK6 inhibitor.Xx_NEWLINE_xXReceived prior HDAC inhibitor therapyXx_NEWLINE_xXParticipants must have radiological or objective evidence of progression on an endocrine and CDK 4/6 inhibitor regimen in the metastatic setting, and/or relapse/progression during or within 12 months of completion of an endocrine and CDK4/6 inhibitor regimen in the adjuvant setting\r\n* Participants must have previously been exposed to CDK4/6 inhibitor therapy in combination with endocrine therapy; exposure to any prior CDK4/6 inhibitor, (including palbociclib, abemaciclib, and ribociclib) is allowed; patients may have a line of endocrine therapy after combination endocrine and CDK4/6 inhibitor exposure\r\n* Participants must have remained on prior endocrine and CDK4/6 therapy in the metastatic setting without progression for at least 6 months prior to study entry\r\n* It is not mandatory to have a CDK 4/6 inhibitor containing regimen as the most recent treatmentXx_NEWLINE_xXPrior treatment with idelalisib, other selective PI3K? inhibitors, or a pan-PI3K inhibitor.Xx_NEWLINE_xXAny previous treatment with an anti-CTLA4, including tremelimumab or any previous treatment with a PD1 or PDL1 inhibitorXx_NEWLINE_xXPrior treatment with a MET inhibitor (e.g. foretinib, crizotinib, cabozantinib, onartuzumab or previous savolitinib) or sunitinb.Xx_NEWLINE_xXSomatic activating mutation in EGFR radiographic progression during treatment with erlotinib or any other EGFR tyrosine kinase inhibitor (TKI) therapiesXx_NEWLINE_xXPatients who have received prior treatment with a MEK inhibitorXx_NEWLINE_xXPrevious treatment with lapatinib, neratinib, afatinib, tucatinib, or other investigational EGFR family receptor tyrosine kinase inhibitor or HER2 tyrosine kinase inhibitorXx_NEWLINE_xXPatients who have a diagnosis for which a PD-(L)-1 inhibitor has been approved must have previously received treatment with one of these therapies. a. Melanoma Dose Expansion: Patients must have histologically confirmed metastatic melanoma (ocular melanoma not included) which has progressed on or after treatment with a PD-(L)1 inhibitor.Xx_NEWLINE_xXIndication A - ASPS: Subjects with no prior therapy or subjects with prior treatment with chemotherapy or an angiogenesis inhibitor (e.g., sunitinib).Xx_NEWLINE_xXPrior receipt of a selective FGFR inhibitor.Xx_NEWLINE_xXMust have received at least 2 prior therapies approved for CRPC; including a prior AR inhibitor (e.g., enzalutamide or apalutamide). (Part 1 only)Xx_NEWLINE_xXAny previous treatment with a PARP inhibitor, including olaparib;Xx_NEWLINE_xXNo evidence of exon 20 T790M mutation after progression on prior EGFR tyrosine kinase inhibitor(TKI) therapy.Xx_NEWLINE_xXNo prior treatment with an EGFR tyrosine kinase inhibitor (TKI)Xx_NEWLINE_xXPatients who have had prior treatment with a histone deacetylase (HDAC) inhibitor (e.g., romidepsin [Depsipeptide], NSC-630176, MS 275, LAQ-824, belinostat [PXD-101], LBH589, MGCD0103, CRA024781, etc); patients who have received compounds with HDAC inhibitor-like activity, such as valproic acid, as anti-tumor therapy should not enroll in this study; patients who have received such compounds for other indications, e.g. valproic acid for epilepsy, may enroll after a 30-day washout periodXx_NEWLINE_xXPatient had prior treatment with an histone deacetylases (HDAC) inhibitor (e.g., romidepsin [Depsipeptide], NSC-630176, MS 275, LAQ-824, belinostat [PXD-101], LBH589, MGCD0103, CRA024781, etc); patients who have received compounds with HDAC inhibitor-like activity, such as valproic acid, as anti-tumor therapy should not enroll in this study; patients who have received such compounds for other indications, e.g. valproic acid for epilepsy, may enroll after a 30-day washout periodXx_NEWLINE_xXSubjects must have a pathologic diagnosis of advanced renal cell carcinoma (RCC) and must have progressed on treatment with a TORC1 inhibitor (such as temsirolimus or everolimus).Xx_NEWLINE_xXPatients receiving valproic acid (VPA), an anticonvulsant drug with HDAC inhibitor properties, will be excluded, unless they are switched to an alternative agent prior to treatment initiation. No wash out period is required.Xx_NEWLINE_xXHistory of prior therapy with any phosphatidylinositol 3-kinase (PI3K) inhibitor (including idelalisib), or any anti-CD37 agentXx_NEWLINE_xXMust have received at least 3 prior lines of therapy including a proteasome inhibitor and an immunomodulatory agent or those who are double refractory to a PI and an immunomodulatory agent and have demonstrated disease progression (DP) on or within 60 days of completion of the last therapy; participants previously treated with an alkylating agent, in addition to an IMiD or proteasome inhibitor, are allowed to enroll in the trialXx_NEWLINE_xXMelanoma with BRAF V600E or V600K mutation-positive melanoma must have progressed on, or were intolerant to, prior BRAF- or MEK-inhibitor therapyXx_NEWLINE_xXPatients must be at least 4 weeks from the last dose of prior PARP inhibitorXx_NEWLINE_xXHas received prior therapy with imatinib or another tyrosine kinase inhibitorXx_NEWLINE_xXPrior therapy with any known inhibitor of MNK1 or MNK2.Xx_NEWLINE_xXPh+ B-ALL if subjects are intolerant to or ineligible for tyrosine kinase inhibitor (TKI) therapy, or have progressed after at least one line of TKI therapyXx_NEWLINE_xXPrior exposure to ALK receptor tyrosine kinase inhibitor, anti-PD1, anti-PDL1 or any drug targeting T-cell checkpoint pathways.Xx_NEWLINE_xXCohort A: Subjects with a FLT3 mutation (e.g. ITD or D835) with prior FLT3 inhibitor treatmentXx_NEWLINE_xXCohort B: Subjects with a FLT3 mutation (e.g. ITD or D835) without prior FLT3 inhibitor treatmentXx_NEWLINE_xXPrior treatment with a licensed or experimental smoothened inhibitor.Xx_NEWLINE_xXRandomized cohort only: Prior treatment with a Janus kinase inhibitor other than ruxolitinib.Xx_NEWLINE_xXPrior treatment with a JAK inhibitor for any indication.Xx_NEWLINE_xXPatients with known EGFR-activating mutations or ALK rearrangements should have received treatment with a targeted kinase inhibitor (e.g., erlotinib, crizotinib) and no longer be considered as a candidate for such treatmentXx_NEWLINE_xXRequiring anticoagulants at therapeutic doses or platelet inhibitor.Xx_NEWLINE_xXPrior history of a hypertensive reaction to a kinase inhibitorXx_NEWLINE_xXPatients may not have taken another histone deacetylase inhibitor (i.e. valproic acid, vorinostat) for at least 2 weeks prior to enrollmentXx_NEWLINE_xXPrior exposure to dasatinib (> 7 days), Bruton’s tyrosine kinase inhibitor exposure, or prior chemotherapy for ALL (up to 7 days of steroids are allowed)Xx_NEWLINE_xXNo prior therapy with an mTOR-pathway inhibitorXx_NEWLINE_xXSubject has received prior treatment with any EGFR tyrosine kinase inhibitorXx_NEWLINE_xXSubjects with any prior exposure to Janus kinase 2 (JAK2) inhibitor therapy (i.e. ruxolitinib or prior pacritinib therapy) are excludedXx_NEWLINE_xXPrior treatment with PI3K inhibitor(s)Xx_NEWLINE_xXPrior treatment with a PI3K/mTOR inhibitor, epidermal growth factor receptor (EGFR) inhibitor, and/or necitumumab.Xx_NEWLINE_xXPrevious treatment with a PI3K or AKT inhibitor.Xx_NEWLINE_xXPrior treatment with BIBF 1120 or any other VEGFR inhibitor within 4 weeksXx_NEWLINE_xXPrior treatment with a BTK inhibitor.Xx_NEWLINE_xXSubjects known to be anaplastic lymphoma kinase (ALK)-fusion/rearrangement mutation positive must have received an ALK inhibitor.Xx_NEWLINE_xXPrior therapy with a known heat shock protein 90 (HSP90) inhibitorXx_NEWLINE_xXCOHORT 2 ONLY: A Smoothened inhibitor must have been previously administered as monotherapyXx_NEWLINE_xXPatients who have received prior treatment with a P13K inhibitorXx_NEWLINE_xXPrior treatment with gamma secretase inhibitor or other Notch signaling inhibitor.Xx_NEWLINE_xXProgressive disease while previously receiving a PI3K inhibitor (e.g. GS-1101 [idelalisib], duvelisib) or a serious/severe AE related to PI3K inhibitor treatmentXx_NEWLINE_xXPrior treatment with afatinib or any other HER2 inhibitor other than trastuzumabXx_NEWLINE_xXPrior monotherapy with an EGFR inhibitor except as maintenance therapyXx_NEWLINE_xXPrior therapy with a mitogen-activated protein kinase kinase (MEK)-inhibitorXx_NEWLINE_xXMust have relapsed/refractory disease after receiving 1 or more lines of therapy, including a Bruton tyrosine kinase (BTK) inhibitor (eg ibrutinib) if approved by the local health authority and commercially accessible. All Arms:Xx_NEWLINE_xXPrior treatment with a PI3K inhibitor or BTK inhibitorXx_NEWLINE_xXPrior systemic treatments with either ipilimumab or a BRAF inhibitor (such as vemurafenib or dabrafenib)Xx_NEWLINE_xXPrior systemic anticancer therapy for SCLC (including previous therapy with a cyclin-dependent kinase [CDK] inhibitor)Xx_NEWLINE_xXPrior treatment with a JAK inhibitor for any indication.Xx_NEWLINE_xXPatients may not previously have received irinotecan, topotecan or other topoisomerase I inhibitorXx_NEWLINE_xXSubjects with a known EGFR mutation must have received previous treatment with an EGFR tyrosine kinase inhibitor; and subjects with a known ALK translocation must have received previous treatment with an ALK inhibitor.Xx_NEWLINE_xXIn countries where anaplastic lymphoma kinase (ALK) inhibitors are available for the treatment of NSCLC, subjects need to have been screened for ALK fusion gene rearrangements and excluded if positive, unless previously treated and progressed on an appropriate tyrosine kinase inhibitor (TKI) therapyXx_NEWLINE_xXThere is no maximum cumulative prior JAK2 inhibitor treatmentXx_NEWLINE_xXPrior therapy with a MEK inhibitorXx_NEWLINE_xXPrior taxane, vincristine, or other microtubule inhibitor chemotherapies for treatment of GBM or other malignancyXx_NEWLINE_xXPrior or current treatment with a c-MET inhibitor or HGF-targeting therapyXx_NEWLINE_xX15. Prior treatment with drugs an FAK inhibitor.Xx_NEWLINE_xXPrior exposure to VEGFR tyrosine kinase inhibitor (small molecule or antibody) or VEGFR antibody.Xx_NEWLINE_xXPrior therapy with an IGF-1R inhibitor.Xx_NEWLINE_xXPrior treatment with an HSP90 inhibitorXx_NEWLINE_xXPrevious treatment with selective/specific BRAF or Methyl Ethyl Ketone (MEK) inhibitor (previous treatment with sorafenib is allowed)Xx_NEWLINE_xXPatients who have had prior VEGF pathway inhibitor, BRAF or MEK inhibitor therapy are ineligible.Xx_NEWLINE_xXNo prior Aurora kinase inhibitorXx_NEWLINE_xXAKT INHIBITOR MK2206 ARM: Previous AKT inhibitor therapyXx_NEWLINE_xXChemotherapy, targeted therapy (such as a tyrosine kinase inhibitor), or radiotherapy must have been completed at least 14 days before administration of T-cells; prior immunotherapy with checkpoint blockade (i.e., PD1 inhibitor, PDL1 inhibitor, or CTL4-antagonist or similar agent) must have been completed more than 1 month before the T-cell infusion\r\n* Chemotherapy must have been completed at least 7 days prior to leukapheresisXx_NEWLINE_xXPatients currently receiving treatment for concurrent active malignancy; prior immunotherapy with checkpoint blockade (i.e., PD1 inhibitor, PDL1 inhibitor, or CTL4-antagonist or similar agent) must have been completed more than 1 month prior to the T-cell infusionXx_NEWLINE_xXPreviously treated on any CDK 4/6 inhibitor.Xx_NEWLINE_xXProgressed on more than one CDK 4/6 inhibitorXx_NEWLINE_xXParts A and B only: Has received mTOR inhibitor(s) as their only prior treatment for ccRCC.Xx_NEWLINE_xXTyrosine Kinase Inhibitor (TKI) within 2 weeks.Xx_NEWLINE_xXCohort 2: Has received prior aromatase inhibitor therapy and is deemed to be resistant to all three (anastrozole, letrozole, exemestane) approved AIs; resistance is defined as progression within 12 months or while on an AIXx_NEWLINE_xXPrior therapy with ceritinib or other ALK or ROS1 inhibitor agentsXx_NEWLINE_xXPatients who have received prior treatment with a selective cyclin-dependent kinase 4/6 (CDK4/6) inhibitorXx_NEWLINE_xXPrior treatment with a Hsp90 inhibitorXx_NEWLINE_xXPatients previously treated with immune checkpoint inhibitor therapy are eligibleXx_NEWLINE_xXPatients previously treated with an mammalian TOR (mTOR) or PI3K inhibitorXx_NEWLINE_xXChemotherapy, targeted therapy (such as a tyrosine kinase inhibitor), or radiotherapy must have been completed at least 14 days prior to administration of T cells; continuation of hormonal therapy (i.e. for breast cancer) is acceptable; prior immunotherapy with checkpoint blockade (i.e. PD1 inhibitor, PDL1 inhibitor, or CTL4-antagonist or similar agent) must have been completed more than 1 month prior to the T cell infusion\r\n* Chemotherapy must have been completed at least 7 days prior to leukapheresisXx_NEWLINE_xXPatients currently receiving treatment for concurrent active malignancy; continuation of hormonal therapy (i.e. for breast cancer) is acceptable; prior immunotherapy with checkpoint blockade (i.e. PD1 inhibitor, PDL1 inhibitor or CTL4-antagonist or similar agent) must have been completed more than 1 month prior to the T cell infusionXx_NEWLINE_xXSubject must have received at least one BCR PI (ibrutinib, idelalisib, or other approved BTK or PI3K inhibitor) and/or venetoclax;Xx_NEWLINE_xXPatients who were taking or have a history of taking letrozole or another aromatase inhibitor.Xx_NEWLINE_xXPatients should not have taken valproic acid, another histone deacetylase (HDAC) inhibitor, for at least 2 weeks prior to enrollmentXx_NEWLINE_xXTreatment with a thiazolidinedione PPAR gamma inhibitor; e.g. Actos® (pioglitazone) and Avandia® (rosiglitzone)Xx_NEWLINE_xXTreatment with a Janus kinase (JAK) inhibitor within 21 days of the planned first dose of MMBXx_NEWLINE_xXCurrent or anticipated use of a strong P-gp inhibitor, strong P-gp inducer, or strong inhibitor of BCRP.Xx_NEWLINE_xXPrior treatment with a phosphoinositide -3 kinase (PI3K) inhibitor, Protein Kinase B Inhibitor is known as AKT inhibitor, or mammalian target of rapamycin (mTOR) inhibitor.Xx_NEWLINE_xXHistory of prior significant toxicity from another MEK inhibitor or ERK inhibitor requiring discontinuation of treatmentXx_NEWLINE_xXPrior treatment with small molecule bromodomain and extra terminal family inhibitorXx_NEWLINE_xXPrior treatment with any CDK4/6 inhibitor therapyXx_NEWLINE_xXPrior treatment with a proteasome inhibitorXx_NEWLINE_xXHas, at the initiation of study drug, received cytotoxic chemotherapy or a Bruton's tyrosine kinase (BTK)-inhibitor (e.g. ibrutinib) within the past 3 weeks or rituximab within the past 2 monthsXx_NEWLINE_xXTreatment with a thiazolidinedione PPAR gamma inhibitor; e.g. Actos® (pioglitazone) and Avandia® (rosiglitazone)Xx_NEWLINE_xXPrior therapy with ALK inhibitor other than crizotinibXx_NEWLINE_xXPrior treatment with a known PARP inhibitorXx_NEWLINE_xXPrevious therapy with histone deacetylase inhibitor.Xx_NEWLINE_xXHave previously received an investigational BET inhibitor (including previous participation in this study or Study ZEN003694-002)Xx_NEWLINE_xXPrior treatment with a spleen tyrosine kinase (SYK) inhibitorXx_NEWLINE_xXHypersensitivity to Janus kinase (JAK) inhibitorXx_NEWLINE_xXPrior therapy with a janus kinase 2 (JAK2) or fms-related tyrosine kinase 3 (FLT3) inhibitorXx_NEWLINE_xXPrior therapy with a JAK inhibitor (other than ruxolitinib for less than 3 months duration and currently on it) or histone deacetylase inhibitor (HDACi); patients that are currently on ruxolitinib for less than 3 months of therapy are eligibleXx_NEWLINE_xXPrior exposure to bruton tyrosine kinase (BTK) inhibitorXx_NEWLINE_xXReceived erlotinib or other EGFR tyrosine kinase inhibitor (TKI) treatment for at least 2 weeks prior to enrollmentXx_NEWLINE_xXConcurrent therapy with a potent cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducer or inhibitor; subjects may enter screening when therapy with the potent inhibitor or inducer is completed and may begin study treatment after 1 week or 5 half-lives, whichever is longerXx_NEWLINE_xXPatients who have received prior treatment with JAK inhibitorXx_NEWLINE_xXMust have received or may still be receiving one or more therapies including octreotide or serotonin synthesis inhibitor (SSI) or other somatostatin analoguesXx_NEWLINE_xXOngoing treatment with any drugs known to prolong the QTc interval, including anti-arrhythmic medications (stable regimen of antidepressants of the selective serotonin reuptake inhibitor (SSRI) class is allowed))Xx_NEWLINE_xXAny number of prior lines of systemic anti-neoplastic therapy are allowed; treatment with =< 1 prior VEGF inhibitor will be allowedXx_NEWLINE_xXPrior treatment with filanesib (ARRY-520) or any other KSP inhibitor.Xx_NEWLINE_xXPrior adjuvant therapy with sorafenib or another Raf/VEGF inhibitorXx_NEWLINE_xXTreatment with a thiazolidinedione PPAR gamma inhibitor; e.g. Actos® (pioglitazone) and Avandia® (rosiglitzone)Xx_NEWLINE_xXPrior treatment with a MEK inhibitor or a CDK4/6 inhibitor.Xx_NEWLINE_xXPrior therapy with a MEK- inhibitorXx_NEWLINE_xXPrior treatment with any BRAF inhibitor or any mitogen-activated protein/extracellular signal-regulated kinase inhibitor.Xx_NEWLINE_xXPrior treatment with a BRAF inhibitor or MEK inhibitorXx_NEWLINE_xXRelapsed or refractory to at least one second generation tyrosine kinase inhibitor (TKI) (dasatinib, nilotinib, bosutinib, ponatinib)Xx_NEWLINE_xXPrior treatment with carfilzomib, filanesib, or any other KSP inhibitor.Xx_NEWLINE_xXHistory of prior significant toxicity from another MEK pathway inhibitor or combination of another MEK and epidermal growth factor receptor (EGFR) inhibitor requiring discontinuation of treatmentXx_NEWLINE_xXPrevious treatment with a combination of a MEK inhibitor with an EGFR inhibitor (applies only to the indication specific expansion cohorts in Stage 2)Xx_NEWLINE_xXPatients are excluded if they have a history of prior treatment with ipilimumab, cluster of differentiation (CD)137 agonist, cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitor or agonist or bavituximabXx_NEWLINE_xXConcurrent use of a strong CYP3A inhibitor. Subjects who have received a strong CYP3A inhibitor prior to entering the study must have discontinued therapy for at least 5 half lives of the prohibited medication.Xx_NEWLINE_xXPrevious treatment with a BRAF or MEK inhibitorXx_NEWLINE_xXTreatment with a thiazolidinedione PPAR gamma inhibitor; e.g. Actos® (pioglitazone), and Avandia® (rosiglitzone)Xx_NEWLINE_xXThe subject has previously been treated with a PI3K inhibitor and taken off treatment due to treatment related AEs.Xx_NEWLINE_xXThe subject has been previously treated with a Mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitor.Xx_NEWLINE_xXPrior PI3Ki or selective FGFR inhibitor treatment (for patients enrolled to expansion part)Xx_NEWLINE_xXNo more than one prior line of antitumor therapy for metastatic disease, excluding prior treatment with tyrosine kinase inhibitors. An interval of at least 1 week is required for washout of the tyrosine kinase inhibitor.Xx_NEWLINE_xXPrior treatment with any Hsp90 inhibitor.Xx_NEWLINE_xXPrior treatment with phosphoinositide 3-kinase (PI3K) inhibitorXx_NEWLINE_xXBisphosphonates/tumor necrosis factor receptor super family, member 11a (RANK)-ligand inhibitor allowed if started prior to study treatmentXx_NEWLINE_xXPatients may not have received prior therapy with an Aurora kinase inhibitorXx_NEWLINE_xXThey have received treatment with orteronel or another lyase inhibitor in the pastXx_NEWLINE_xXAromatase Inhibitor (AI) resistant, defined as:Xx_NEWLINE_xXPrior treatment with an mTOR inhibitor.Xx_NEWLINE_xXPrior treatment with a BRAF inhibitor (including but not limited to dabrafenib, vemurafenib, and XL281/BMS-908662) or a MEK inhibitor (including but not limited to trametinib, AZD6244, and RDEA119) or ipilimumab or any other agent targeting a T-cell immunomodulatory pathway (including, but not limited to CTLA-4, PD-1, 4-1BB, OX40, GITR, CD27, and CD28)Xx_NEWLINE_xXPrior anti-cancer treatment with any HSP90 inhibitorXx_NEWLINE_xXPatients who have received prior treatment with a CDK inhibitor within 12 months of study enrollment.Xx_NEWLINE_xXPrior treatment with a PI3K inhibitorXx_NEWLINE_xXThe last dose of anti-VEGF tyrosine kinase inhibitor must be at least 7-days but not more than 56-days from enrollmentXx_NEWLINE_xXPrior therapy with a MEK inhibitor.Xx_NEWLINE_xXAny prior exposure to any VEGF or VEGF inhibitor including, but not limited to, bevacizumab, cediranib, vandetanib, sunitinib, pazopanib, aflibercept, or sorafenib (Phase II)Xx_NEWLINE_xXPart B, Part C and Part D only: Previous treatment with dabrafenib or any BRAF inhibitor, trametinib or another MEK inhibitor, or and Extracellular signal-regulated kinase inhibitor (exception: prior treatment with sorafenib is permitted). Patients who have received prior dabrafenib or another BRAF inhibitor may enrol into Part B4. Patients who have had prior dabrafenib or BRAF inhibitor therapy may enroll in Part C or Part D if they have had prior benefit to dabrafenib or BRAF inhibitor monotherapy, as determined by the investigator.Xx_NEWLINE_xXMust be 14 days from administration of non-cytotoxic agents (e.g., bevacizumab (except COHORT 2b), interferon, tamoxifen, thalidomide, cis-retinoic acid, tyrosine kinase inhibitor, etc.).Xx_NEWLINE_xXPatients are allowed prior VEGFR-tyrosine kinase inhibitor (TKI); patients will be stratified based on prior VEGFR-TKI therapyXx_NEWLINE_xXPart 2 ONLY: Previous treatment with dabrafenib, another RAF inhibitor, or a mitogen-activated protein kinase (MEK) inhibitor (exception: prior treatment with sorafenib is permitted).Xx_NEWLINE_xXPatients must not have received prior treatment with any VEGF receptor tyrosine kinase inhibitor (e.g., cediranib, sunitinib, pazopanib, sorafenib); however, prior treatment with bevacizumab is allowedXx_NEWLINE_xXPrior treatment with selumetinib or another specific mitogen-activated protein kinase (MEK)1/2 inhibitor (unless the subject meets criteria for re-treatment)Xx_NEWLINE_xXPrior treatment with cabozantinib (or other MET inhibitor) or CB-839Xx_NEWLINE_xXRequirement for continued proton pump inhibitor after randomizationXx_NEWLINE_xXHave received any prior treatment with an IDH inhibitor.Xx_NEWLINE_xXPrior treatment with an Akt inhibitor (prior PI3K or mTOR inhibitors are allowed)Xx_NEWLINE_xXPatient has received treatment previously with a PARP inhibitor.Xx_NEWLINE_xXPrior treatment with a known poly (ADP-ribose) polymerase (PARP) inhibitorXx_NEWLINE_xXPrior treatment with a known poly (ADP-ribose) polymerases (PARP) inhibitorXx_NEWLINE_xXARQ 197 is a sensitive substrate for 2C19 and 3A4, a strong inhibitor for 2C19 and moderate inhibitor by in vitro data only for 3A4; temsirolimus is a sensitive substrate for CYP 3A4 and a weak inhibitor of CYP2D6 and CYP3A4/5; per the UWinRx Drug Interaction Policy, the following medications are contraindicated or must be used with cautionXx_NEWLINE_xXNo prior therapy with a BRAF inhibitor or mitogen-activated protein kinase kinase (MEK) inhibitor or leflunomideXx_NEWLINE_xXPrior treatment with pan-histone deacetylases (HDAC) or mammalian target of rapamycin (mTOR) inhibitorXx_NEWLINE_xXPatients who have received prior treatment with an mTOR inhibitor (e.g. sirolimus, temsirolimus, everolimus)Xx_NEWLINE_xXPrior use of valproic acid or any other histone deacetylase (HDAC) inhibitor for lymphoma treatmentXx_NEWLINE_xXAny number of prior regimens for recurrent or metastatic SCCHN (i.e. palliative treatment) but without cetuximab or another EGFR inhibitorXx_NEWLINE_xXPrior treatment with an EGFR inhibitor other than cetuximab at any timeXx_NEWLINE_xXPrior treatment with an EGFR inhibitor as part of a regimen for recurrent or metastatic SCCHNXx_NEWLINE_xXPrior treatment with Src family kinase (SFK) inhibitor at any timeXx_NEWLINE_xXPrior therapy with an HSP90 inhibitorXx_NEWLINE_xXHave received a selective phosphoinositide-3-kinase alpha isoform (PI3K-alpha) inhibitorXx_NEWLINE_xXPrior treatment with fulvestrant, phosphoinositide 3-kinase (PI3K) inhibitor, or mechanistic target of rapamycin (mTOR) inhibitor for ABC or MBCXx_NEWLINE_xXPrior therapy with other CYP17 inhibitor(s) or investigational agent(s) targeting the androgen receptor for metastatic prostate cancerXx_NEWLINE_xXPatient received prior treatment for MM with a proteasome inhibitor and an immunomodulatory drug, unless not a candidate for a proteasome inhibitor or an immunomodulatory drug.Xx_NEWLINE_xXPrior treatment with an HDAC inhibitor.Xx_NEWLINE_xXAny history of prior treatment with ipilimumab or prior CD137 agonist or cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) inhibitor or agonistXx_NEWLINE_xXPatients who have received prior treatment with a P13K inhibitorXx_NEWLINE_xXa. ?2 prior therapies including proteasome inhibitor and immunomodulatory agent (IMiD)Xx_NEWLINE_xXPrevious treatment with a BRAF or MEK inhibitor.Xx_NEWLINE_xXPrior treatment with trastuzumab or other HER2-directed therapies or with a mammalian target of rapamycin (mTOR) inhibitor within 12 months of study entry (when cancer was not definitely hormone refractory)Xx_NEWLINE_xXPatients who have received prior treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus)Xx_NEWLINE_xXPatients who have received prior treatment with an mammalian target of rapamycin (mTOR) inhibitor (e.g., sirolimus, temsirolimus, everolimus)Xx_NEWLINE_xXPrior therapy with lapatinib or an ErbB2 inhibitor other than trastuzumab (including but not limited to trastuzumab-DM1 and neratinib) and capecitabine;Xx_NEWLINE_xXAt least 28 days from prior treatment (including adjuvant interferon) except in the case of a v-raf murine sarcoma viral oncogene homolog B1 (BRAF) inhibitor (such as vemurafenib); concurrent treatment with a BRAF inhibitor +/- mitogen activate protein kinase kinase (MEK) inhibitor is permitted; concurrent treatment with an anti-programmed death-1 (PD1) agent is permittedXx_NEWLINE_xXPrior neoadjuvant therapy (endocrine therapy or chemotherapy) or CDK4/6 inhibitorXx_NEWLINE_xXPrior treatment with ibrutinib, a PD-1 inhibitor, a PD-L1 inhibitor, or a CTLA-4 inhibitorXx_NEWLINE_xXPatients must be resistant to, intolerant of, or ineligible for JAK2 inhibitor therapy, based on severe anemia or thrombocytopeniaXx_NEWLINE_xXPrior EGFR tyrosine kinase inhibitor (TKI) therapy with progression, and documented EGFR T790M mutation on tumor biopsy; however, this need not be only second lineXx_NEWLINE_xXSubject has received a prior EGFR inhibitor within 6 days prior to the first dose of study drug.Xx_NEWLINE_xXMust have received ? 2 prior anti-MM therapies including a proteasome inhibitor and an IMiD. The most recent proteasome inhibitor must not have been carfilzomib.Xx_NEWLINE_xXPrior FGFR inhibitor therapyXx_NEWLINE_xXPrior treatment with selective inhibitor of nuclear export (SINE) inhibitorXx_NEWLINE_xXRequirement of therapy with a UGT1A1 Inhibitor, or use within 7 days of enrollment on this protocolXx_NEWLINE_xXPrior therapy with a BRAF inhibitorXx_NEWLINE_xXCOHORT 2 ONLY: Prior treatment with a VEGF inhibitor (e.g. sunitinib, bevacizumab, sorafenib or other dedicated VEGF inhibitor)Xx_NEWLINE_xXCOHORT 1 ONLY: Prior treatment with a VEGF inhibitor (e.g. sunitinib, bevacizumab, sorafenib or other dedicated VEGF inhibitor)Xx_NEWLINE_xXPrior treatment with a BRAF or mitogen-activated protein kinase kinase (MEK) inhibitor for metastatic melanoma (treatment in the adjuvant setting is allowed)Xx_NEWLINE_xXPrevious treatment with a phosphatidylinositol 3-kinase (P1-3K) inhibitorXx_NEWLINE_xXPrior treatment with vemurafenib or other BRAF inhibitor within 42 days of first dose of study drugXx_NEWLINE_xXHistory of significant toxicity related to another phosphatidylinositol 3-kinase (PI3K) inhibitor or mammalian target of rapamycin (mTOR) inhibitor requiring treatment discontinuationXx_NEWLINE_xXPrior treatment with PI3K inhibitorXx_NEWLINE_xXHistory of significant toxicity related to mTOR inhibitor requiring treatment discontinuationXx_NEWLINE_xXPrior allergic reaction or severe intolerance (meeting the criteria for a serious adverse event, a grade 3 or 4 AE, or permanent treatment discontinuation) to a poly ADP ribose polymerase (PARP) inhibitor.Xx_NEWLINE_xXPrior allergic reaction or severe intolerance (meeting the criteria for a serious adverse event, a grade 3 or 4 AE, or permanent treatment discontinuation) to a poly ADP ribose polymerase (PARP) inhibitor.Xx_NEWLINE_xXPrior exposure to lenvatinib or mammalian target of rapamycin (mTOR) inhibitorXx_NEWLINE_xXScheduled to begin, or within 18 months of beginning, treatment with an aromatase inhibitor at the time of the first study assessment (i.e., TP0)Xx_NEWLINE_xXNo prior use of a selective estrogen receptor modulator (SERM) or aromatase inhibitor (AI) for chemopreventionXx_NEWLINE_xXEligible to receive, but not yet begun, aromatase inhibitor therapyXx_NEWLINE_xXTaking any of the following drugs at the time of study participation: epidermal growth factor receptor inhibitor, topoisomerase 1 inhibitor (camptothecin, irinotecan); buspirone, benzodiazepines, zolpidem, calcium channel blockers (such as felodipine, nifedipine, verapamil); digoxin or quinidine; codeine or fentanyl; phenytoin, propranolol, rifampin, or theophyllineXx_NEWLINE_xXReceived sirolimus within the 14 days prior to starting study as voriconazole is a potent inhibitor of sirolimus metabolismXx_NEWLINE_xXPatients undergoing concurrent cytotoxic chemotherapy and radiation therapy (concurrent Herceptin and/or tamoxifen/aromatase inhibitor allowed)Xx_NEWLINE_xX>= 5/10 arthralgia (in hands, wrist, knees, or hips) while being treated with anastrozole or letrozole which is felt by the patient to be caused by their aromatase inhibitor, as measured by verbally addressing the following question: please rate your pain by picking a number, from 0 to 10 (0 being none and 10 being as bad as you can imagine) that best describes your pain from your aromatase inhibitor breast cancer medication on AVERAGE, over the past week\r\n* Note: Patients may, or may not, be taking non-opioid analgesicsXx_NEWLINE_xXConcurrent use of the aromatase inhibitor exemestaneXx_NEWLINE_xXSubjects who have previously received JAK inhibitor therapyXx_NEWLINE_xXBe on same oral tyrosine kinase inhibitor (TKI) for >= 3 monthsXx_NEWLINE_xXUse of a Factor Xa inhibitor (e.g. apixaban, rivaroxaban, or edoxaban) =< 3 months prior to randomizationXx_NEWLINE_xXHave previously received an investigational BET inhibitor (including previous participation in this study or Study ZEN003694-001)Xx_NEWLINE_xXPatients may not have received cytotoxic, biologic or small molecule kinase inhibitor systemic therapy for at least 3 weeks prior to the first dose of study treatmentXx_NEWLINE_xXPrior treatment with a Bruton's tyrosine kinase (BTK) inhibitorXx_NEWLINE_xXGroup 3: Patients must have a confirmed diagnosis of unresectable GIST that has progressed and/or patients must have experienced intolerance to imatinib and not received additional kinase-inhibitor therapy. Patients must not have a known D842V mutation in PDGFR?.Xx_NEWLINE_xXPrior treatment with an inhibitor that is targeted primarily to FGFRsXx_NEWLINE_xXPrior treatment with everolimus or another mammalian target of rapamycin (mTOR) inhibitor (temsirolimus)Xx_NEWLINE_xXConcurrent use of calcineurin-inhibitor plus sirolimus (either agent alone is acceptable)Xx_NEWLINE_xXPatients may have had prior HER1/EGFR inhibitor therapy but must have fully recovered from any skin toxicities prior to registrationXx_NEWLINE_xXCurrent use or use within past two weeks of an monoamine oxidase inhibitor (MAOI)Xx_NEWLINE_xXCurrently using select CYP2D6 inhibitor or inducer medicationsXx_NEWLINE_xXSubjects who have not yet initiated but plan to undergo dosing with a tyrosine kinase inhibitor (TKI) or Raf inhibitor, either alone or with a MEK inhibitor, for treatment of metastatic melanoma, colon cancer, hepatic cell carcinoma, or thyroid cancerXx_NEWLINE_xXMyeloproliferative neoplasms (MPN): must have < 5% peripheral / marrow blasts\r\n* Note: Prior use of a Janus kinase 2 (JAK2) inhibitor is allowed up to 4 weeks before day 0 of allogeneic hematopoietic cell transplantation (alloHCT)Xx_NEWLINE_xXAny patient anticipating or scheduled to receive a tyrosine kinase inhibitor, FLT3 inhibitor, or JAK2 inhibitor (outside of this study) post-HCTXx_NEWLINE_xXPatients currently on endocrine therapy (tamoxifen, ralozifene or an aromatase inhibitor)Xx_NEWLINE_xXUse of any selective estrogen receptor modulator or aromatase inhibitor within 6 months of randomization, including, but not limited to: tamoxifen, raloxifene, arzoxifene, acolbifene, anastrozole, exemestane, and letrozoleXx_NEWLINE_xXUse of endocrine therapy (selective estrogen receptor modulator, aromatase inhibitor, gonadotrophin releasing hormone [GnRH] agonist) within 6 months of start of studyXx_NEWLINE_xXUse of any selective estrogen receptor modulator or aromatase inhibitor (tamoxifen, raloxifene, arzoxifene, acolbifine, anastrozole, exemestane, letrozole) within the previous 6 monthsXx_NEWLINE_xXProton pump inhibitor use at least once daily for at least twelve months prior to enrolment, and stable dose of PPI for the three months before enrolmentXx_NEWLINE_xXPatients may not have had prior treatment with mTOR, peptidase inhibitor 3, skin-derived (PI3) kinase or Akt inhibitorsXx_NEWLINE_xXPrior treatment with a dual mTORC1/mTORC2 inhibitor (CC-223 arms only) or BTK inhibitor (PCI-32765) (CC-292 arms only). [Prior treatment with rapamycin analogues, PI3K or AKT inhibitors, lenalidomide and rituximab are allowed].Xx_NEWLINE_xXHormonal therapy (tamoxifen, an aromatase inhibitor, or Lupron) is not permitted during radiation or during the subsequent 4 weeks (the entire dose-limiting toxicity [DLT] window)Xx_NEWLINE_xXHave received at least 3 prior lines of therapy, including a proteasome inhibitor [PI] and an immunomodulatory agent [IMiD] OR have disease that is double refractory to a PI and IMiDXx_NEWLINE_xXPrior exposure to approved receptor tyrosine kinase inhibitors is permitted; at least 5 half-lives must have elapsed since the completion of the kinase inhibitor and the initiation of study treatmentXx_NEWLINE_xXPrior exposure to ABT888 or other PARP inhibitors is permitted in all cohorts except the cohort evaluating BRCA-mutated PARP inhibitor naive patients, where prior PARP inhibitor treatment will not be permitted; prior exposure to cyclin-dependent kinase inhibitors other than SCH727965 is permittedXx_NEWLINE_xXSubjects on a potent CYP3A4 inhibitor or CPY3A4 inducer who cannot be changed to another medication are excludedXx_NEWLINE_xXPatients with melanoma must also meet the following criteria: a. If melanoma is BRAF wild-type or has BRAF mutations that are not amenable to BRAF inhibitor therapy, and the patient is a candidate for immunotherapy, must have received ipilimumab; b. If melanoma is positive for the V600E or V600K BRAF mutation, must have received at least one line of prior therapy with a BRAF-specific inhibitor; either alone or in combination.Xx_NEWLINE_xXLess than 2 weeks or 5 plasma half-lives (whichever is greater) since last use of a medication or ingestion of an agent, beverage, or food that is a potent inhibitor or inducer of the cytochrome P450 (CYP)3A or CYP2C9 pathways (patients should discontinue taking any regularly-taken medication that is a potent inhibitor or inducer of the CYP3A or CYP2C9 pathways)Xx_NEWLINE_xXNo history of prior CDK 4/6 inhibitor useXx_NEWLINE_xXParticipants who are receiving any other investigational agents; history of prior PI3K, mTOR or CDK 4/6 inhibitor use for breast cancerXx_NEWLINE_xXDiagnosis of MM with relapsed or refractory disease and have had at least 3 different prior lines of therapy including proteasome inhibitor (e.g., bortezomib or carfilzomib) and immunomodulatory therapy (IMiD; e.g., lenalidomide or pomalidomide), or have double refractory disease to a proteasome inhibitor and IMiD, defined as progression on or within 60 days of treatment with these agents.Xx_NEWLINE_xXPrior or ongoing treatment with a PARP1 inhibitorXx_NEWLINE_xXPostmenopausal women, men, or premenopausal women for whom endocrine therapy (tamoxifen, aromatase inhibitor [AI] with or without ovarian suppression or fulvestrant), with or without a CDK4/6 inhibitor is planned after FES-PET/CT is completed.Xx_NEWLINE_xXCurrent or prior androgen deprivation therapy; a history of use of a 5-alpha reductase inhibitor is allowed, provided it was discontinued at least one month prior to study entryXx_NEWLINE_xXCandidate to undergo immune checkpoint inhibitor (ICI) therapy for SCLC or NSCLC (ICI as any line of chemotherapy is acceptable) as deemed by individual’s treating oncologistXx_NEWLINE_xXParticipants who have received any treatment regimen including a VEGF-R inhibitor such as bevacizumab or cediranib, or plan to receive such agents as part of initial management for glioblastomaXx_NEWLINE_xXImmune checkpoint inhibitor therapy within 30 days of the first dose of study treatmentXx_NEWLINE_xXPrior treatment with a topoisomerase I inhibitorXx_NEWLINE_xXPrior treatment with an antibody-drug conjugate (ADC) that consists of an exatecan derivative that is a topoisomerase I inhibitor (eg, DS-8201a)Xx_NEWLINE_xXPrior treatment with a check-point inhibitor targeting PD-1, unless not a candidate.Xx_NEWLINE_xXRenal Cell Carcinoma: documented histological or cytological diagnosis of renal cell cancer with a clearcell or papillary component; progression following at least two prior lines of standard therapy including a checkpoint inhibitor and an anti-VEGFR inhibitor; archival tissue or fresh tumor biopsyXx_NEWLINE_xXHistory of receiving treatment with any c-MET signaling pathway inhibitor (marketed or investigational agents)Xx_NEWLINE_xXPrior receipt of a selective FGFR4 inhibitor within the last 6 months.Xx_NEWLINE_xXPrior exposure to a SINE compound (i.e. an XPO-1 inhibitor), including selinexor.Xx_NEWLINE_xXHas received prior treatment with enhancer of zeste homolog (EZH) inhibitorXx_NEWLINE_xXCohort 1 only: prior treatment with previous VEGFR active multikinase inhibitorXx_NEWLINE_xXCohort 2 only: more than one prior treatment with VEGFR active multikinase inhibitor prior to original start of lenvatinibXx_NEWLINE_xXALK positive NSCLC patients must either be treatment naive in the advanced setting or have had disease progression on or intolerance to at least 1 previous ALK inhibitor; ROS1 positive NSCLC patients must either be treatment naive in the advanced setting or have had disease progression on or intolerance to at least 1 previous ROS1 inhibitorXx_NEWLINE_xXCurrent or prior androgen deprivation therapy; previous use of a 5-alpha reductase inhibitor is allowed, provided it was discontinued at least one month prior to study entryXx_NEWLINE_xXPatients should be potential candidates for therapy with an EGFR tyrosine kinase inhibitor or with an anti-EGFR monoclonal antibody by clinical criteriaXx_NEWLINE_xXCurrent or recent use of reproductive hormone therapy, tamoxifen, aromatase inhibitor or other estrogen inhibitors within the last 90 days, which may affect biomarkersXx_NEWLINE_xXPrior treatment with mammalian target of rapamycin (mTOR) inhibitors will be allowed as long as the patient did not have >= grade 3 toxicity attributed to the mTOR inhibitor with prior therapyXx_NEWLINE_xXPrior treatment with an mTOR inhibitor (including sirolimus) is allowed; however, patients with >= grade 3 toxicities with an mTOR inhibitor are excludedXx_NEWLINE_xXHistory of a prior intolerable toxicity, in the opinion of the investigator from another B-cell lymphoma (BCL)-2 family protein inhibitor study.Xx_NEWLINE_xXPrior therapy should include at least a proteasome inhibitor (PI), an immunomodulatory drug (IMid), an alkylating agent, and a steroid and should be refractory or intolerant to at least 1 PI and at least 1 IMid.Xx_NEWLINE_xXNon-clear cell histology: 0-3 prior systemic therapies and may include mTOR inhibitorXx_NEWLINE_xXTreatment with gemfibrozil (or other strong CYP2C8 inhibitor) within 14 days before the first dose of TAK-580.Xx_NEWLINE_xXHistory of prior significant toxicity from another MEK or ERK inhibitor requiring discontinuation of treatmentXx_NEWLINE_xXMinimum of 3 prior lines of therapy including an immunomodulatory drug (IMiD) and a proteasome inhibitor (PI)Xx_NEWLINE_xXPatients with Philadelphia chromosome (Ph) positive (+) pre-B cell ALL OR Ph+ MPAL will be eligible if they have been refractory to or intolerant of treatment with at least 1 second-generation or third-generation tyrosine kinase inhibitor (TKI)Xx_NEWLINE_xXParticipants must not have had prior treatment with an EGFR kinase inhibitor, EGFR directed therapy or investigational agentXx_NEWLINE_xXProgressive Disease (PD) during prior aromatase inhibitor (AI) therapy.Xx_NEWLINE_xXDiscontinuation on prior BTK inhibitor or PI3K delta inhibitor due to adverse events within prior 9 monthsXx_NEWLINE_xXProgression on prior BTK or PI3K delta inhibitorXx_NEWLINE_xXCML in blast phase, resistant or intolerant to tyrosine kinase inhibitor therapyXx_NEWLINE_xXPrevious treatment with dabrafenib, trametinib, other RAF inhibitor, other MEK or ERK inhibitorXx_NEWLINE_xXPatients with EGFR and ALK alterations should have been treated with at least 1 line of targeted tyrosine kinase inhibitorXx_NEWLINE_xXHas had prior chemotherapy, within 2 weeks prior to study treatment; patients on targeted therapy (tyrosine kinase inhibitor) may go on the study after 5 days off therapyXx_NEWLINE_xXRequires treatment with a strong CYP 3A inhibitorXx_NEWLINE_xXPatients who have received adequate prior treatment with a highly selective FGFR inhibitorXx_NEWLINE_xX