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.