Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before planned first dose of study drug
Receipt 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 agents
The participant has received prior treatment with a small molecule kinase inhibitor or a hormonal therapy (including investigational kinase inhibitors or hormones) within 4 weeks or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment; note: participants with prostate cancer currently receiving luteinizing hormone-releasing hormone (LHRH) or gonadotropin-releasing hormone (GnRH) agonists may be maintained on these agents
Chemotherapy, monoclonal antibody, or small molecule kinase inhibitor =< 21 days prior to first administration of study treatment
Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 14 days before the first dose of study treatment
The subject has received prior treatment with a small molecule kinase inhibitor or a hormonal therapy (including investigational kinase inhibitors or hormones) within 14 days or 5 half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment -OR- the subject has ever taken Cabozantinib; Note: subjects with prostate cancer currently receiving luteinizing hormone releasing hormone (LHRH) or gonadotropin releasing hormone (GnRH) agonist may be maintained on these agents
Receipt 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 agents
Receipt of any type of small molecular kinase inhibitor (including investigational kinase inhibitors) within 2 weeks of enrollment or receipt of any anti-cancer therapy (including investigational therapy, monoclonal antibodies, cytokine therapy) within 3 weeks of enrollment
Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 14 days before the first dose of study treatment
The subject has received prior treatment with a small molecule kinase inhibitor or a hormonal therapy (including investigational kinase inhibitors or hormones) within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment
Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 14 days before the first dose of study treatment
The subject has received prior treatment with a small molecule kinase inhibitor or a hormonal therapy (including investigational kinase inhibitors or hormones) within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment
No prior treatment with a small molecule kinase inhibitor or a hormonal therapy within 14 days or 5 half-lives (whichever is longer)
Prior treatment with a small molecule kinase inhibitor or a hormonal therapy (including investigational kinase inhibitors or hormones) within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment
The subject has received prior treatment with a small molecule kinase inhibitor or a hormonal therapy (including investigational kinase inhibitors or hormones) within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment
Receipt of any type of small molecular kinase inhibitor (including investigational kinase inhibitors) within 2 weeks or 5 half-lives (whichever is shorter) of enrollment or receipt of any anti-cancer therapy (including investigational therapy, monoclonal antibodies, cytokine therapy) within 3 weeks of enrollment
The subject has received prior treatment with a small molecule kinase inhibitor or a hormonal therapy (including investigational kinase inhibitors or hormones) within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment with the exception of patients receiving prior abiraterone or ketoconazole; for patients receiving prior abiraterone or ketoconazole, they must discontinue the medication within 5 half-lives of the compound before the first dose of study treatment in order to participate in this study; Note: subjects with prostate cancer currently receiving luteinizing-hormone-releasing hormone (LHRH) or gonadotropin-releasing hormone (GnRH) agonists must be maintained on these agents
The participant has received prior treatment with a small molecule kinase inhibitor or a hormonal therapy (including investigational kinase inhibitors or hormones) within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment
Prior treatment with a small molecule kinase inhibitor or a hormonal therapy (including investigational kinase inhibitors or hormones) within 14 days or five half-lives of the compound or active metabolites, whichever is longer, or before the first dose of study treatment
The subject has received prior treatment with a small molecule kinase inhibitor within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment
The subject has received prior treatment with a small molecule kinase inhibitor or a hormonal therapy (including investigational kinase inhibitors or hormones) within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment
Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitors) within 2 weeks of enrollment or receipt of any anti-cancer therapy (including investigational therapy, monoclonal antibodies, cytokine therapy) within 4 weeks of enrollment
Patients 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 treatment
Received JAK inhibitor therapy after allo-HSCT for any indication. Treatment with a JAK inhibitor before allo-HSCT is permitted.
CRLF2 rearrangement with JAK1 or JAK2 mutation (JAK+)
CRLF2 rearrangement without JAK mutation
Other JAK pathway alterations (eg, JAK2 fusions, erythropoietin receptor (EPO-R) fusions, SH2B3 deletions, interleukin-7 receptor-alpha (IL7RA) mutations) with or without CRLF2 rearrangement
Patients who have previously been treated with an IL-6, JAK or STAT inhibitor for any indication, such as ruxolitinib or tocilizumab
Participants who were treated with prior JAK inhibitors for aGvHD; except when the participant achieved complete or partial response and has been off JAK inhibitor treatment for at least 8 weeks prior to Cycle 1 Day 1
Patients previously treated with a Janus kinase (JAK) inhibitor
Hypersensitivity to any JAK inhibitor
Prior 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.
Patients must not have received prior JAK1 inhibitor therapy.
Prior treatment with JAK2 inhibitor therapy is not excluded; a JAK2 inhibitor will need to be stopped 1-2 days prior to starting conditioning regimen
Subjects who have previously received JAK inhibitor therapy
Treatment with ruxolitinib or other JAK inhibitor in the past
Any previous use of Janus kinase (JAK) inhibitor, osimertinib, or other EGFR-directed therapy for T790M-mt NSCLC.
PART 2: Received JAK inhibitor for at least 8 weeks immediately prior to conditioning and be able to continue until Day -4 pre-transplant
Patients cannot have any other form of chemotherapy for their MPN (other than hydroxyurea); specifically prior interferon or JAK2 inhibitors are prohibited
Any previous Janus kinase 2 gene (JAK2) inhibitor treatment prior to study enrollment, with the exception of ruxolitinib
Hypersensitivity to Janus kinase (JAK) inhibitor
Documented progressive disease during or after JAK inhibitor therapy
MF PATIENTS: Patients must be intermediate I risk or beyond and meet the following:\r\n* In need of treatment\r\n* Intolerant or refractory to ruxolitinib (or other investigational Janus kinase [JAK]-inhibitors) OR unlikely to benefit from ruxolitinib\r\n* Ineligible or refusal to undergo stem cell transplantation
Any prior or concomitant use of another JAK inhibitor
Previously received JAK inhibitor therapy for any indication.
Prior use of a JAK1 or JAK2 inhibitor
Patients must be resistant to, intolerant of, or ineligible for Janus kinase (JAK)2 inhibitor therapy, or have refused such therapy
History of prior janus kinase (JAK) or STAT3 inhibitor treatment
Previous allergic reactions to janus kinase (JAK) inhibitors or excipients
Prior therapy with ruxolitinib or other JAK inhibitors
Any chemotherapy (e.g., hydroxyurea), immunomodulatory drug therapy (e.g., thalidomide), immunosuppressive therapy, corticosteroids > 10 mg/day prednisone or equivalent, growth factor treatment (e.g., erythropoietin) or Janus kinase (JAK) inhibitor therapy =< 14 days prior to registration
Any 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 ruxolitinib
MF 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 assessment
Subjects previously treated with anagrelide or JAK inhibitors.
Prior treatment with a JAK inhibitor for any indication.
Subjects with any prior exposure to Janus kinase 2 (JAK2) inhibitor therapy (i.e. ruxolitinib or prior pacritinib therapy) are excluded
Prior treatment with a JAK inhibitor for any indication.
Prior treatment with more than 2 JAK2 inhibitors or with pacritinib
There is no maximum cumulative prior JAK2 inhibitor treatment
Treatment with a Janus kinase (JAK) inhibitor within 21 days of the planned first dose of MMB
Hypersensitivity to Janus kinase (JAK) inhibitor
Prior therapy with a janus kinase 2 (JAK2) or fms-related tyrosine kinase 3 (FLT3) inhibitor
Prior 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 eligible
Patients who have received prior treatment with JAK inhibitor
Patients must be off myeloproliferative neoplasm (MPN) directed therapy, such as Janus kinase (JAK)-inhibitors, for at least 2 weeks prior to administration of the study drug; NOTE: This does not include supportive transfusion, or hydroxyurea; these must be stopped prior to first day of treatment, but no wash –out period is required
Patients must be resistant to, intolerant of, or ineligible for JAK2 inhibitor therapy, based on severe anemia or thrombocytopenia
Prior treatment with more than two Janus kinase 2 (JAK2) inhibitors or with pacritinib
Moderate or severe cGVHD diagnosed and staged per National Institute of Health (NIH) criteria; responses to Janus kinase (JAK) inhibitors have not been restricted to specific organs, so any organ involvement is eligible
Hypersensitivity to JAK inhibitors
Subjects who have previously received JAK inhibitor therapy
Part B only: Prior treatment with SYK or Janus Kinase (JAK) inhibitors, except MF subjects.
Prior treatment with a JAK inhibitor or with an investigational agent, device, or procedure within 21 days of enrollment.
Myeloproliferative 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)
Any patient anticipating or scheduled to receive a tyrosine kinase inhibitor, FLT3 inhibitor, or JAK2 inhibitor (outside of this study) post-HCT
Received a prior IDH inhibitor.
Prior treatment with dasatinib, or any BCR-ABL1 inhibitor other than imatinib
The 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 participate
Previous treatment with XL184 (cabozantinib) or another MET/HGF inhibitor (tivantinib, crizotinib)
Patients 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 eligible
Prior therapy with PLX3397 unless discontinued for intolerance (i.e., non-progression on prior kinase inhibitor)
Prior treatment with a smoothened inhibitor (SMOi) and/or hypomethylating agent.
Any previous treatment with pevonedistat or other NEDD8 inhibitor
Prior treatment with a mitogen activated-protein kinase (MAPK) inhibitor
Prior treatment (at least 1 full treatment cycle) with a farnesyltransferase inhibitor.
Prior exposure to a WNT inhibitor
Previous therapy with histone deacetylase (HDAC) inhibitor.
Previous treatment with any prior BET inhibitor therapy
Prior therapy with AT13387 or another HSP90 inhibitor
Crizotinib, or any other cMET inhibitor or HGF-targeting inhibitor.
The subject has received cabozantinib or another c-Met inhibitor (please note ARQ 197 is not considered a MET inhibitor for purposes of this study)
Prior treatment with an MDM2 inhibitor.
Previous treatment with sunitinib or kinase inhibitor other than imatinib Wash-out
Prior therapy with any known inhibitor of MNK-1 or MNK-2.
Prior treatment with small molecule bromodomain and extra terminal (BET) family inhibitor.
Subjects who were intolerant to a BTK inhibitor
Participants who have received a prior inhibitor of Wee1 kinase activity
Prior treatment with a RAF inhibitor
Previous treatment with vismodegib or any other hedgehog pathway inhibitor
Prior treatment with WEE1 inhibitor
Prior treatment with Mcl-1 inhibitor.
Prior exposure to a BTK or BCL-2 inhibitor
Prior treatment with a drug of the focal adhesion kinase (FAK) inhibitor class.
Participants enrolling to the MET cohort who have received a prior MET inhibitor may not be on anticoagulant therapy unless the investigator has deemed it safe to temporarily hold to facilitate the baseline tumor biopsy
Participants who have received prior treatment with a CHK1 inhibitor.
Prior treatment (at least 1 full treatment cycle) with a farnesyltransferase inhibitor.
Prior treatment with Bromodomain and Extra-Terminal (BET) inhibitor
Previous therapy with histone deacetylase (HDAC) inhibitor
Prior treatment with CTLA-4 inhibitor
Prior treatment with an hepatocyte growth factor (HGF)/cMet inhibitor such as rilotumumab, crizotinib, MetMAb, or ARQ197
No history of prior BTK-inhibitor-containing therapy.
Patients having received any prior BCL2 inhibitor therapy
Has received prior treatment with PT2977 or another HIF-2? inhibitor
No platelet inhibitor drugs within 5 days prior to infusion and during the immediate study 6 Day follow-up period.
Subject has received a prior targeted IDH2 inhibitor
Previous treatment with epacadostat, SD-101, or any other IDO inhibitor or CpG molecule
The participant has received a prior c-Met inhibitor
Patients having received any prior BCL2 inhibitor therapy
Prior 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.
Prior treatment with venetoclax or other Bcl-2 inhibitor
Cancer 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.
Prior exposure to docetaxel, selinexor, or another selective inhibitor of nuclear transport (SINE) compound
Prior or concurrent treatment with AR antagonists or CYP17 enzyme inhibitor.
Anticipated ribonuclease inhibitor (RAI) treatment within 18 weeks of treatment
Prior aromatase inhibitor therapy first initiated > 4 weeks prior to study enrollment
AZD1775 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 alternatives
Subjects with prior treatment with an MDM2 inhibitor
Prior treatment with crizotinib, or any other cMET or HGF inhibitor
Prior systemic therapy with a small molecule oral kinase inhibitor, including but not limited to: pazopanib, sunitinib, sorafenib, everolimus, sirolimus, vemurafenib, dasatinib and trametinib
Has had prior exposure to tazemetostat or other inhibitor(s) of enhancer of zeste homologue-2 (EZH2)
Prior receipt of an indoleamine 2,3-dioxygenase (IDO) inhibitor
Prior BTK inhibitor treatment.
Previous treatment with a c-MET inhibitor or HGF-targeting therapy (applies only to Group 2)
Prior treatment with an MDM2 inhibitor.
Patients who have received prior treatment with a phosphoinositide 3-kinase (P13K) inhibitor
Patients must not have received prior HSP90 inhibitor therapy
Beginning adjuvant aromatase inhibitor therapy, with no previous use within the last 6 weeks
Primary 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 treatment
Prior receipt of a PIM inhibitor
Prior treatment with an FTase inhibitor
Prior 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;
Prior treatment with ASN007 or another ERK1/2 inhibitor
Prior treatment with an antibody-drug conjugate (ADC) which consists of an exatecan derivative that is a topoisomerase I inhibitor (eg, DS-8201)
Prior treatment with any Hsp90 inhibitor.
Prior treatment with crizotinib or any other cMET or HGF inhibitor
Prior treatment with any Hsp90 inhibitor.
Prior use of trametinib or other MAPK inhibitor in any context
Prior treatment with hsp90 inhibitor
Patients who have received prior treatment with a P13K inhibitor
Patient 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, Antileukotriene
Prior treatment with an investigational EZH2 inhibitor
A history of prior significant toxicity, other than thrombocytopenia, from another Bcl-2 family protein inhibitor
Progressed during treatment or within 12 months of completion of adjuvant therapy with an aromatase inhibitor
Prior use of aromatase inhibitor therapy apart from assisted reproduction
Prior treatment with vorinostat or other HDAC inhibitor
Prior exposure to ibrutinib or to a BCR inhibitor (eg Btk or PI3 kinase or Syk inhibitors) or a BCL-2 inhibitor (eg venetoclax)
Patients who have received prior treatment with nintedanib or any other VEGFR inhibitor are not eligible
Current 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 days
If 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 months
Prior therapy with an Abelson murine leukemia viral oncogene homolog (ABL) kinase inhibitor such as nilotinib, ponatinib, dasatinib, or imatinib
Have received prior treatment with an IDH1 inhibitor.
Prior 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.
Subjects with prior treatment with an MDM2 inhibitor
Prior treatment with a TORC1, dual TORC1/2 inhibitor, or BCL-2/xL inhibitor
Prior treatment with a histone deacetylase inhibitor
Prior therapy with an angiogenesis inhibitor
Prior therapy with a hedgehog inhibitor
Any previous treatment with a HDAC inhibitor, including citarinostat
Use of a protease inhibitor for any indication within three months prior to start of study treatment
Any 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 sofosbuvir
Prior therapy with another hedgehog inhibitor
Patients who have received prior treatment with a P13K inhibitor or RAD001 (if discontinued for toxicity)
Has had prior exposure to tazemetostat or other inhibitor(s) of EZH2
Prior treatment with inhibitor of MET or HGF
Prior exposure to ibrutinib or to a BCR inhibitor or a BCL-2 inhibitor.
Prior receipt of an IDO inhibitor.
Prior receipt of a BET inhibitor (Treatment Group B only).
Prior receipt of an LSD1 inhibitor including INCB059872 (Treatment Group C only).
Immediate 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).
Prior exposure to a BCL-2 inhibitor (eg, venetoclax/ABT-199)
Has had prior exposure to tazemetostat or other inhibitor(s) of enhancer of zeste homolog 2 (EZH2)
Has had prior exposure to tazemetostat or other inhibitor(s) of enhancer of zeste homologue-2 (EZH2)
Prior therapy with histone deacetylase (HDAC) inhibitor.
Patients who have received prior treatment with a mutant-specific IDH1 inhibitor (with the exception of glioma patients)
Prior treatment with a MET inhibitor or HGF targeting agent
Histologically 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.
Prior therapy with an IDO1 or arginase 1 inhibitor.
Use of 5-alpha reductase inhibitor within the 3 months prior to dosing.
Group 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)
Treatment with a complement inhibitor at any time.
Previous treatment with a c-MET inhibitor or HGF-targeting therapy.
Prior exposure to a BTK inhibitor
Previous 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).
EGFR, 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.
Prior therapy with a histone deacetylase (HDAC) inhibitor
History of a prior significant toxicity, other than thrombocytopenia, from another Bcl-2 family protein inhibitor
Previous treatment with any aminopeptidase inhibitor
Participants with concurrent use of calcineurin-inhibitor plus sirolimus (either agent alone is acceptable)
Patients may not have received previous therapy with a MET inhibitor
Prior therapy with everolimus or an aromatase inhibitor
Prior treatment with an HGF/cMet inhibitor such as rilotumumab, crizotinib, MetMAb (onartuzumab), or ARQ197 (tivantinib)
Patients who have received prior treatment with a phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (P13K) inhibitor
Prior or current treatment with a cMet inhibitor
Patients who have received or been treated with an tumor necrosis factor-alpha inhibitor such as adalimumab (Humira) within four weeks of starting on study
Prior treatment with any Hsp90 inhibitor.
No prior MET inhibitor is allowed
Prior therapy with HDAC inhibitor
Participants who have a history of prior MM treatment with panobinostat, or an alternative histone deacetylase (HDAC)-inhibitor
Have received prior therapy with an immunomodulatory agent, a proteosome inhibitor, and glucocorticoids
No prior treatment with any HSP90 or histone deacetylase (HDAC) inhibitor compound is allowed
Patients who have received prior treatment with a phosphatidylinositol 3 kinase (P13K) inhibitor
Prior anti-neoplastic treatment with any HSP90 or histone deacetylase (HDAC) inhibitor compound
Previous therapy with a topoisomerase I or II inhibitor
Prior treatment with CGM097 or other p53/HDM2-interaction inhibitor
History of hormone replacement therapy (estrogens with or without progestin) or an aromatase inhibitor (anastrazole, letrozole, exemestane) within 8 weeks prior to day 1
Prior therapy with a PDGFR or c-Met inhibitor
Prior treatment with a histone deacetylase (HDAC) inhibitor
Prior treatment with an HSP90 inhibitor (e.g. 17-AAG, IPI-504, AUY922, STA-9090 [ganetespib] etc.)
Prior histone deacetylases (HDAC) inhibitor, deacetylase (DAC) inhibitor, heat shock protein (Hsp)90 inhibitor or valproic acid for the treatment of cancer
a documented NTRK fusion and a clinical history of relapse following a response to a prior TRK inhibitor
a documented NTRK fusion unresponsive to a prior TRK inhibitor
a documented NTRK fusion and a clinical history of intolerance to a prior TRK inhibitor
Received prior HDAC inhibitor therapy
Prior therapy with any known inhibitor of MNK1 or MNK2.
Prior treatment with a licensed or experimental smoothened inhibitor.
Randomized cohort only: Prior treatment with a Janus kinase inhibitor other than ruxolitinib.
Prior history of a hypertensive reaction to a kinase inhibitor
Prior treatment with BIBF 1120 or any other VEGFR inhibitor within 4 weeks
Prior treatment with a BTK inhibitor.
Prior therapy with a known heat shock protein 90 (HSP90) inhibitor
Patients who have received prior treatment with a P13K inhibitor
Prior treatment with gamma secretase inhibitor or other Notch signaling inhibitor.
Prior or current treatment with a c-MET inhibitor or HGF-targeting therapy
15. Prior treatment with drugs an FAK inhibitor.
Prior therapy with an IGF-1R inhibitor.
Prior treatment with an HSP90 inhibitor
No prior Aurora kinase inhibitor
AKT INHIBITOR MK2206 ARM: Previous AKT inhibitor therapy
Patients 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 infusion
Cohort 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 AI
Prior treatment with a Hsp90 inhibitor
Patients 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 infusion
Prior treatment with small molecule bromodomain and extra terminal family inhibitor
Previous therapy with histone deacetylase inhibitor.
Must have received or may still be receiving one or more therapies including octreotide or serotonin synthesis inhibitor (SSI) or other somatostatin analogues
Prior treatment with filanesib (ARRY-520) or any other KSP inhibitor.
Prior treatment with any Hsp90 inhibitor.
Patients may not have received prior therapy with an Aurora kinase inhibitor
They have received treatment with orteronel or another lyase inhibitor in the past
Aromatase Inhibitor (AI) resistant, defined as:
Prior anti-cancer treatment with any HSP90 inhibitor
Have received any prior treatment with an IDH inhibitor.
ARQ 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 caution
Prior treatment with Src family kinase (SFK) inhibitor at any time
Prior therapy with an HSP90 inhibitor
Prior treatment with an HDAC inhibitor.
Patients who have received prior treatment with a P13K inhibitor
Prior treatment with selective inhibitor of nuclear export (SINE) inhibitor
Previous treatment with a phosphatidylinositol 3-kinase (P1-3K) inhibitor
Patients who discontinue monoamine oxidase (MAO)-inhibitor (I)’s within 14 days prior to starting the investigational drug
Received sirolimus within the 14 days prior to starting study as voriconazole is a potent inhibitor of sirolimus metabolism
Concurrent use of the aromatase inhibitor exemestane
Prior treatment with an inhibitor that is targeted primarily to FGFRs
Concurrent use of calcineurin-inhibitor plus sirolimus (either agent alone is acceptable)
Prior treatment with a topoisomerase I inhibitor
Prior treatment with an antibody-drug conjugate (ADC) that consists of an exatecan derivative that is a topoisomerase I inhibitor (eg, DS-8201a)
Prior treatment with a check-point inhibitor targeting PD-1, unless not a candidate.
History of receiving treatment with any c-MET signaling pathway inhibitor (marketed or investigational agents)
Prior exposure to a SINE compound (i.e. an XPO-1 inhibitor), including selinexor.
Has received prior treatment with enhancer of zeste homolog (EZH) inhibitor
Cohort 1 only: prior treatment with previous VEGFR active multikinase inhibitor
Cohort 2 only: more than one prior treatment with VEGFR active multikinase inhibitor prior to original start of lenvatinib
History of a prior intolerable toxicity, in the opinion of the investigator from another B-cell lymphoma (BCL)-2 family protein inhibitor study.
Prior therapy with any CDK inhibitor.
Prior treatment with CDK4/6 inhibitor
Patient who received any CDK4/6 inhibitor
Prior treatment with a CDK 4/6 inhibitor.
Patient has a known hypersensitivity to ribociclib or any of its excipients, or prior treatment with CDK 4/6 inhibitor
For enrollment to arm 2: participants must have a confirmed CDK4 or CDK6 high-level amplification, identified via DFCI/BWH OncoPanel or any CLIA-certified method
Participants who have received prior treatment with a CDK4/6 inhibitor
Prior exposure to transcriptional kinase family CDK inhibitors, such as the CDK7 and CDK9 inhibitors alvocidib (Flavopiridol), dinaciclib, and seliciclib. Exception: previous exposure to cell cycle CDK inhibitors such as CDK4 and CDK6 (eg, palbociclib) is allowed
Previous treatment with a CDK 4/6 inhibitor or an mTOR inhibitor
Prior therapy with any CDK inhibitor
Prior treatment on a CDK inhibitor
have a diagnosis of metastatic ER+ breast cancer in patients who received and progressed on at least two lines of endocrine therapy, with one that included a CDK4/CDK6 inhibitor (e.g., palbociclib or ribociclib);
Received a prior CDK4/6 inhibitor
No prior therapy with any CDK 4/6 inhibitors.
Prior use of CDK4/6 inhibitors
Patient who received any CDK4/6 inhibitor
Patients who have received prior treatment with a selective CDK4 inhibitor
Previous CDK4/6 inhibitor
Patient 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 setting
Received any previous treatment with alvocidib or any other CDK inhibitor
Documented 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,
Participants who have received prior treatment with a CDK4/6 inhibitor
Patients who have been in the past enrolled on a study of a Cdk inhibitor
Prior treatment with CDK4/6 inhibitor
Prior treatment with any CDK4/6 inhibitor.
Group 1 - Patients must not have received prior treatment with any CDK4/6 inhibitors
Group 2 - Patients must have disease progression while on or within one month after CDK4/6 inhibitor based therapy
Group 3 - Patients must have disease progression while on or within one month after CDK4/6 inhibitor based therapy (except those patients who received prior LEE011 based therapy).
Prior treatment with any CDK 4/6 inhibitor
Patient who has received a prior CDK4/6 inhibitor
Prior treatment with any CDK 4/6 inhibitor.
Prior treatment with a CDK4/6 inhibitor and/or bazedoxifene
Patient who received any CDK4/6 inhibitor.
The participant has previously received treatment with any CDK4 and CDK6 inhibitor.
Participants 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 treatment
Previously treated on any CDK 4/6 inhibitor.
Progressed on more than one CDK 4/6 inhibitor
Prior treatment with any CDK4/6 inhibitor therapy
Prior treatment with a MEK inhibitor or a CDK4/6 inhibitor.
Patients who have received prior treatment with a CDK inhibitor within 12 months of study enrollment.
Prior neoadjuvant therapy (endocrine therapy or chemotherapy) or CDK4/6 inhibitor
No history of prior CDK 4/6 inhibitor use
Patients 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 malignancy
Concurrent use or anticipated need for medications that are mainly metabolized by UGT1A9 including their administration within 7-days prior to the first dose of study drug (e.g., raloxifene, valproic acid, propofol, propranolol, dapagliflozin, darexaban, mycophenolic acid, and tapentadol)
Concomitant therapy with valproic acid/valproate-containing therapies
Patients who are being treated with Valproic Acid for any of its indication (epilepsy, mood disorder) must be excluded or must stop using the medication.
Patients requiring concurrent administration of valproic acid are not eligible for this trial
Prior treatment with histone deacetylase (HDAC) inhibitors (e.g. valproic acid, Zolinza (SAHA), romidepsin (Istodax)
Has taken valproic acid, or another histone deacetylase inhibitor, within 2 weeks prior to study day 1
Prior histone deacetylase (HDAC), deacetylase (DAC), heat shock protein (HSP)90 inhibitors or valproic acid for the treatment of cancer is allowed
Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first panobinostat treatment
Patients who have received histone deacetylase (HDAC) inhibitors (including valproic acid, entinostat, vorinostat) are excluded
Patients with a prior history of treatment with histone deacetylase (HDAC) inhibitors (e.g., SNDX-275/entinostat, LAQ-824, LBH589, PXD-101/belinostat, etc); patients who have received valproic acid will be excluded from this study
Needing valproic acid for any medical condition during the study or within 5 days prior to first panobinostat treatment
Patients should not have taken valproic acid or another histone deacetylase inhibitor for at least 2 weeks prior to enrollment
History of severe allergic reaction to sunitinib or valproic acid; inability to receive sunitinib or valproic acid
Previous treatment with sunitinib or valproic acid for uveal melanoma
Active treatment with valproic acid for non-oncological conditions, if this cannot be safely switched to an alternative agent
Prior myelosuppressive chemotherapy or other investigational drug therapy within the last 6 months prior to initiation of sunitinib or valproic acid
Patients taking concomitant histone deacetylase (HDAC) inhibitors; use of HDAC inhibitor like compounds such as valproic acid for epilepsy is permitted if there is at least a 2 week wash out
Any condition that would prohibit patient from initiating valproic acid; current or prior valproic acid treatment is allowed (do not need to be >= lower limit of normal [LLN] for laboratory for enrollment)
History of valproic acid (VPA) use
Patients must not have received valproic acid within 30 days of study entry
Patients requiring concomitant therapy with phenytoin, phenobarbital, carbamazepine, or valproic acid
Prior anti-cancer treatment with MLN9708 (ixazomib), histone deacetylase (HDAC), deacetylase (DAC), heat shock protein (HSP)90 inhibitors or valproic acid
Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first panobinostat treatment
Use of any UDP glucuronosyltransferase 1 family, polypeptide A9 (UGT1A9) inhibitor including: acitretin, amitriptyline, androsterone, cyclosporine, dasatinib, diclofenac, diflunisal, efavirenz, erlotinib, estradiol (17-beta), flutamide, geftinib, gemfibrozil, glycyrrhetinic acid, glycyrrhizin, imatinib, imipramine, ketoconazole, lineoleic acid, mefenamic acid, mycophenolic acid, niflumic acid, nilotinib, phenobarbital, phenylbutazone, phenytoin, probenecid propofol, quinidine, ritonavir, Sorafenib, sulfinpyrazone, valproic acid and verapamil from screening through follow-up period
Patients asking or who have had prior treatment with a drug like vorinostat (i.e., valproic acid) within the last 30 days
Participants should not have taken valproic acid or another histone deacetylase inhibitor for at least 2 weeks prior to study enrollment
Patient 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 period
Patients should not have taken valproic acid or another histone deacetylase inhibitor for at least 2 weeks prior to enrollment
Patient needing valproic acid during the study or within 5 days prior to first dose
Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first PANOBINOSTAT treatment
Patients receiving histone deacetylase (HDAC) inhibitors or compounds with HDAC inhibitor like activity, such as valproic acid, are ineligible; patients who have received such agents may enroll on this study after a 14-day washout period
Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first panobinostat treatment
Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first panobinostat treatment
Valproic acid for the treatment of cancer
Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first panobinostat treatment
Prior histone deacetylase (HDAC), deacetylase (DAC), heat shock protein 90 (HSP90) inhibitors or valproic acid for the treatment of cancer
Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first panobinostat treatment
Allergy to valproic acid
Patients 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 period
Patient 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 period
Concurrent use of valproic acid is not allowed
Patients 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.
Prior HDAC, deacetylase (DAC), heat shock protein (HSP)90 inhibitors or valproic acid for treatment of cancer
Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first panobinostat treatment
Patients will be excluded if they are receiving Valproic Acid (VPA) therapy.
Patients may not have taken another histone deacetylase inhibitor (i.e. valproic acid, vorinostat) for at least 2 weeks prior to enrollment
Concurrent use of other histone deacetylase inhibitors (e.g. valproic acid) are prohibited except for histone deacetylase (HDAC) inhibitors or HDAC-inhibitor like agents used for non-cancer treatment (e.g. epilepsy), where a 14 day washout is allowed
RECURRENT/ PROGRESSIVE DIPG (STRATUM 1): Patients have had valproic acid within 28 days prior to enrollment
Prior histone deacetylases (HDAC), deacetylase (DAC), heat shock protein 90 (HSP90) inhibitors or valproic acid for the treatment of cancer
Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first LBH589 treatment
Patients should not have taken valproic acid, another histone deacetylase (HDAC) inhibitor, for at least 2 weeks prior to enrollment
Patients will be excluded if they have received previous therapy with HDAC, DAC, HSP90 inhibitors or valproic acid anticancer therapy. Valproic acid therapy is not allowed for any reason while on this study.
Patients must not be receiving valproic acid
Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first panobinostat treatment
Treatment with valproic acid within 14 days prior to initiation of study and during the study
Prior use of valproic acid or any other histone deacetylase (HDAC) inhibitor for lymphoma treatment
Use of valproic acid for any medical condition while receiving protocol treatment or within 5 days prior to first panobinostat dose
For subjects assigned to take vorinostat, prior exposure to vorinostat or other known histone deacetylase (HDAC) inhibitors for cancer therapy; patients should not have taken valproic acid, another histone deacetylase inhibitor, for at least 2 weeks prior to study enrollment; note: this criterion does NOT apply to subjects treated on the Expansion Cohort (accruals post February 1, 2013)
Prior therapy with other histone deacetylase (HDAC) inhibitors, including valproic acid
Patients requiring concurrent administration of valproic acid are also excluded
Patients currently taking valproic acid
Histone deacetylase (HDAC), deacetylase (DAC), heat shock protein (HSP)90 inhibitors or valproic acid for the treatment of cancer within 30 days; only Food and Drug Administration (FDA) approved drug are vorinostat and romidepsin the rest are considered investigational and are not allowed
Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first PANO treatment
Any contraindication to dexamethasone or valproic acid such as known allergies or sensitivity
Participants who have previously received a cyclin-dependent kinase (CDK) 4/6 inhibitor
For Part I (abemaciclib + endocrine therapy): The participant must have demonstrated evidence of disease progression on a Cyclin Dependent Kinase 4 (CDK4) and Cyclin Dependent Kinase 6 (CDK6) inhibitor (either palbociclib or ribociclib) plus endocrine therapy for advanced or metastatic disease as the most recent therapy immediately preceding study entry. The participant should remain on the current endocrine therapy while receiving abemaciclib.
Prior therapy with any cyclin-dependent kinase (Cdk) 4 inhibitor
one 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.
Prior therapy with a cyclin-dependent kinase (CDK) inhibitor
History of exposure to alvocidib or any other cyclin-dependent kinase 9 (CDK9) inhibitor.
Arm 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;
Prior therapy with any cyclin-dependent kinase (CDK) inhibitor
Prior treatment with any cyclin dependent kinase (CDK) inhibitor
Has been previously treated with a cyclin-dependent kinase (CDK) inhibitor
For 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.
Prior treatment with drug targeting cyclin-dependent kinase (CDK) family
Prior cyclin-dependent kinase (CDK)4/6 inhibitor exposure
received prior treatment with any cyclin-dependent kinase (CDK) 4 and CDK 6 inhibitor
Have 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.
Have 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.
Have 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)
Disease 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.
Have received treatment with a prior cyclin-dependent kinase (CDK4) and CDK 6 inhibitor.
Prior therapy with any cyclin-dependent kinase 4/6 (CDK4/6) inhibitor
Prior systemic anticancer therapy for SCLC (including previous therapy with a cyclin-dependent kinase [CDK] inhibitor)
Patients who have received prior treatment with a selective cyclin-dependent kinase 4/6 (CDK4/6) inhibitor
Stage I Arm B: history of significant toxicity related to cyclin-dependent kinase (CDK)4/6 inhibitor, bone marrow transplant or extensive radiotherapy to ?25 percent (%) of bone marrow Stage II: