Key Eligibility Criteria Details

• Subject has documented diagnosis of MM and measurable disease, defined as any of the following:
  • M-protein ≥ 0.5 g/dL by serum protein electrophoresis (sPEP) or 
  • M-protein ≥ 200 mg/24-hour urine collection by urine protein electrophoresis (uPEP) or
  • For subjects without measurable disease in sPEP or uPEP: serum free light chain (sFLC) levels > 100 mg/L (10 mg/dL) involved light chain and an abnormal kappa/lambda FLC ratio.
• Subject has received 1 to 3 prior lines of antimyeloma therapy. (Note: One line can contain several phases [eg, induction, (with or without) hematopoietic stem cell transplant, (with or without) consolidation, and/or (with or without) maintenance therapy
• Must have received prior treatment with a lenalidomide-containing regimen
• Must have achieved minimal response or better to at least 1 prior antimyeloma therapy
• Must have documented disease progression during or after their last antimyeloma therapy
• ECOG PS 0-2
• May not have had progression during treatment or within 60 days of the last dose of a proteasome inhibitor
• If prior treatment with a bortezomib containing regimen, must have had a best response of minimal response or better and the subject could not have discontinued bortezomib due to toxicity
• No prior allo transplant
• No plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome or clinically significant light-chain amyloidosis
• No known CNS involvement of myeloma
• No grade 2 or higher peripheral neuropathy
• No other malignancy within 5 years
•  

Key Eligibility Criteria Details

• Histologically confirmed advanced, relapsed, or refractory hematologic malignancies
• Have already received currently available standard of care therapies
• No know CNS involvement
• ECOG PS 0-2 (0-1 for dose escalation phase)
• May have received auto or allo SCT
• Not currently candidate for auto or allo SCT
• No acute GVHD, but chronic GVHD allowed if not requiring steroids and GI tract not affected such that absorption of oral drugs are impared.
• Must be able to take oral medication
• For Multiple Myeloma
  • Measurable disease with either serum M-protein ≥1 g/dl, urine M-protein ≥200mg/24h, or abnormal serum free light-chain ratio and abnormal light chain values
  • Must have received prior tx with both immunomodulatory agent and a proteasome inhibitor
• For Lymphoma
  • HL or NHL (B-cell or T-cell) relapsed or refractory to at least 1 line of prior therapy
• For AML/MDS
  • Relapsed or refractory disease after at least one prior line of standard therapy
  • M3 (APL) is allowed if potentially curative therapies are no longer an option
• For CML
  • Must have received at least 2 lines of prior therapy, and each line must have used a standard TKI alone or in combination
  • If T315I mutation is present must have received ponatinib if a candidate
• For CLL
  • Must have received at least 1 line of prior therapy

Key Eligibility Criteria Details

• Multiple myeloma
• Refractory (progressed on or within 60 days) to most recent treatment
• Must have received >2 lines of prior therapy which must have included at least 2 consecutive cycles of each immune modulatory drug (IMiD) and a proteasome inhibitor alone or in combination
• Measurable disease at screening defined as one or more of the following:
  • Serum IgG, IgA, or IgM M-protein >0.5 g/dL
  • Urine M-protein >200 mg excreted in 24-hour collection sample
  • Involved serum free light chain >100 mg/L provided the FLC ratio is abnormal
• ECOG PS <2
• No prior treatment with pomalidomide, elotuzumab, or any PD-1/PD-L1 inhibitor
• No MGUS, Smoldering myeloma, Waldenstrom’s, amyloidosis, POEMS syndrome, or active plasma cell leukemia (20% peripheral blood of plasma cells or absolute plasma cell count of 2 x10^9/L)
• No active autoimmune disease
• No active infection or uncontrolled severe CV or pulmonary disease
• No chronic steroid use within 14 days of enrollment
• No known HBV/HCV/HIV
• No Grade >2 peripheral neuropathy
• Auto transplant allowed as long as at least 12 weeks prior
• Allo transplant allowed as long as at least 1 year prior

Key Eligibility Criteria Details

• Measurable disease required
• ECOG PS <1
• Brain mets allowed but must not be active, cannot require steroids, have at least one measurable lesion outside of brain
• Excluded tumors:
  • No Pancreatic
  • No endometrial with ER>10%
  • No ovarian
  • No breast
  • No esophageal
  • No gastric
  • No glioma
  • No hepatocellular carcinoma
  • No lymphoma (except primary CNS lymphoma)
  • No leukemia
  • No melanoma
  • No MDS
  • No lung cancer
  • No renal cell
  • No bladder
• Must not have had other cancer within 2 years
• No prior PD-1/L-1 or CTLA-4 therapy
• No autoimmune disease
• No active steroids
• No known HIV, HBV, or HCV
• See "malignancy" list for accepted tumor types

Key Eligibility Criteria Details

• Multiple myeloma either
  • 3rd line after failure of BOTH proteasome inhibitor and IMiD OR
  • 4th line regardless of prior therapies
• Measurable disease activity as indicated by serum or urine M-protein, serum free light chain, biopsy-proven plasmacytoma, >5% bone marrow plasma cells.
• No plasma cell leukemia
• No CNS disease
• No severe autoimmune diseas
• No chronic pulmonary disease
• ANC (>1000/uL), Pplatelet count (>50,000/uL), hemoglobin (>8 g/dL),
• ALT and AST (each <3.0 x upper limit of normal), total bilirubin (<2 mg/dL), creatinine clearance (>30 mL/min),
• Cardiac ejection fraction >45%

Key Eligibility Criteria Details

• ECOG PS 0-1

• Age 18-80 years old

• Must have CLL/SLL requiring treatment per Hallek, 2008

• Must have at least one clinically measurable lesions defined as

  • Nodal lesion measuring >1.5cm in longest diameter and >1.0cm in longest perpendicular diameter OR

  • Spleen measuring >14cm in longest vertical dimension with a minimum of 2 cm enlargement OR

  • Liver measuring >20 cm in longest vertical dimenstion with a minimum of 2 cm of enlargement OR

  • Peripheral blood B lymphocyte count >5000/uL

• For single agent and obinutuzumab combo must have relapsed refractory disease as follows:

  • Must have received either prior chemoimmunotherapy or therapy with an approved BTK inhibitor unless significant co-morbidities or contraindications

• For ibrutinib combo arm, must have not received prior treatment with ibrutinib or BTK inhibitors and must have high-risk disease defined as follows:

  • 17p- and/or TP53 mutation positive in treatment naïve CLL OR

  • 17p- and/or TP53 mutation positive, and/or complex karyotype and/or progression <24 months after completion of 1st line chemoimmunotherapy in relapsed/refractory CLL

• Subjects with R/R SLL or CLL with bulky disease (LN>5.0cm) may only be enrolled after discussion with sponsor medical monitor

• Must have adequate lab values

• No prior allo or auto SCT within 12 months

• No known HIV/HBV/HCV

• No significant peripheral neuropathy

• No impaired cardiac function

Key Eligibility Criteria Details

• Histologically or cytologically confirmed advanced unresectable or metastatic solid malignancy
• Positive biomarker results from a CLIA certified lab, either tissue or blood sample
• ROS1 gene fusion positivity
• No non-small lung cancer (NSCLC)
• ECOG PS 0-2
• No symptomatic CNS metastases
• No known HIV/HBV/HCV
• No other malignancy within 3 years of study
• No prior treatment with crizotinib

Key Eligibility Criteria Details

• Histologically or cytologically confirmed advanced unresectable or metastatic solid malignancy
• Positive biomarker results from a CLIA certified lab, either tissue or blood sample
• No primary CNS malignancy
• One of the following PIK3CA mutations:
  • R88Q
  • ​G106A/D/R/S/V
  • K111N/R/E
  • G118D
  • N345D/H/I/K/S/T/Y
  • C420R
  • E453A/D/G/K/Q/R/V
  • E542A/D/G/K/Q/R/V
  • E545A/D/G/K/L/Q/R/V
  • Q546E/H/L/P/R
  • M1043I/T/V
  • H1047D/I/L/M/P/Q/R/T/Y
  • G1049A/C/D/R/S
  • Others only with study medical monitor approval
• ECOG PS 0-2
• No symptomatic CNS metastases
• No known HIV/HBV/HCV
• No other malignancy within 3 years of study
• No anti-hyperglycemic medication (no treated T2DM or T1DM)

Key Eligibility Criteria Details

• Histologically or cytologically confirmed advanced unresectable or metastatic solid malignancy
• Positive biomarker results from a CLIA certified lab, either tissue or blood sample
• No breast cancer (breast cancer is excluded)
• Either ERBB2 (HER2) amplification defined as a copy number of 6 or higher via FISH, CISH or DNA NGS assay OR
• Any of the following ERBB2 mutations:
  • 222C; R226S; E265K; D277H; G292R; G309A/E; S310F/Y; C311R/S; E321G; C334S; S418T; A440T; P551L; R552S; S653C; V659E; G660D; R678Q; T733I; L755P/S_T759del; I767M; L768S; D769H/N/Y; Y772_A775dup; A775_G776ins(SVMA/VVMA/YAMA/YVMA/YVMD); G776delins(VC/VV/LC); V777L; G778_P780dup; V779A/L; T798M; L841V; V842I; N857S; T862A; L869R; H878Y; R896C​​G
• ​TMB must be <10 mutations/megabase
• ECOG PS 0-2
• No symptomatic CNS metastases
• No known HIV/HBV/HCV
• No other malignancy within 3 years of study
• No prior treatment with crizotinib
• No active autoimmune disease

Key Eligibility Criteria Details

• Histologically or cytologically confirmed advanced unresectable or metastatic solid malignancy
• Positive biomarker results from a CLIA certified lab, either tissue or blood sample
• No breast cancer (breast cancer is excluded)
• Either ERBB2 (HER2) amplification defined as a copy number of 6 or higher via FISH, CISH or DNA NGS assay OR
• Any of the following ERBB2 mutations:
  • 222C; R226S; E265K; D277H; G292R; G309A/E; S310F/Y; C311R/S; E321G; C334S; S418T; A440T; P551L; R552S; S653C; V659E; G660D; R678Q; T733I; L755P/S_T759del; I767M; L768S; D769H/N/Y; Y772_A775dup; A775_G776ins(SVMA/VVMA/YAMA/YVMA/YVMD); G776delins(VC/VV/LC); V777L; G778_P780dup; V779A/L; T798M; L841V; V842I; N857S; T862A; L869R; H878Y; R896C​​G
• Must ALSO have one of the following alterations
  • ​TMB > or =10 mutations/megabase
  • MSI-h
  • dMMR (negative IHC for MLH1, MSH2, MSH6, or PMS2_
• ECOG PS 0-2
• No symptomatic CNS metastases
• No known HIV/HBV/HCV
• No other malignancy within 3 years of study
• No prior treatment with crizotinib
• No active autoimmune disease

Key Eligibility Criteria Details

• Histologically or cytologically confirmed advanced unresectable or metastatic solid malignancy
• Positive biomarker results from a CLIA certified lab, either tissue or blood sample
• Not Non-small cell lung cancer (NO NSCLC)
• ALK gene fusion positivety defined as a 3' AALK fusion with a protein coding 5' gene fusion partner, predicted to be in frame with an intact kinase domain
• ECOG PS 0-2
• No symptomatic CNS metastases
• No known HIV/HBV/HCV
• No other malignancy within 3 years of study
• No prior treatment with crizotinib

Key Eligibility Criteria Details

• Histologically or cytologically confirmed advanced unresectable or metastatic solid malignancy
• Positive biomarker results from a CLIA certified lab, either tissue or blood sample
• Either PTEN protein loss as determined by a CLIA or equivalently certified immunohistochemistry assay OR
• PTEN loss of function defined as PTEN dominant negative missense mutations or deleterious in-frame and missense mutations affecting protein function
• ECOG PS 0-2
• No symptomatic CNS metastases
• No known HIV/HBV/HCV
• No other malignancy within 3 years of study
• No prior treatment with crizotinib
• No insuline dependent diabetes

Key Eligibility Criteria Details

• Histologically or cytologically confirmed advanced unresectable or metastatic solid malignancy
• Positive biomarker results from a CLIA certified lab, either tissue or blood sample
• One of the following mutations in AKT:
  • ​AKT 1 : E17K, L52R, or Q79K
  • AKT 2 : E17K
  • AKT 3: E17K, L51R, or Q78K
• ECOG PS 0-2
• No symptomatic CNS metastases
• No known HIV/HBV/HCV
• No other malignancy within 3 years of study
• No prior treatment with crizotinib
• No insulin dependent diabetes

Key Eligibility Criteria Details

• Histologically or cytologically confirmed advanced unresectable or metastatic solid malignancy
• Positive biomarker results from a CLIA certified lab, either tissue or blood sample
• Tumor mutational burden-high (TMB-H) determined by CLIA opr quivalently certified assay, via tissue or blood
• No prior treatment with anti-PD1 or anti-PD-L1 agents
• ECOG PS 0-2
• No symptomatic CNS metastases
• No known HIV/HBV/HCV
• No other malignancy within 3 years of study
• No prior treatment with crizotinib
• No active autoimmune disease

Key Eligibility Criteria Details

• Histologically or cytologically confirmed advanced unresectable or metastatic solid malignancy
• Positive biomarker results from a CLIA certified lab, either tissue or blood sample
• Microsatellite instability high (MSI-h) or deficient mismatch repair dMMR
• No prior treatment with anti-PD1 or anti-PD-L1 agents
• ECOG PS 0-2
• No symptomatic CNS metastases
• No known HIV/HBV/HCV
• No other malignancy within 3 years of study
• No prior treatment with crizotinib
• No active autoimmune disease

Key Eligibility Criteria Details

At least 3 months/3 cycles of anti-leukemic tx immediatelyprior to trial
At least PR according to NCI-WG criteria after last dose of 2nd/3rd line treatment
ECOG PS 0-2
No fludarabine-refractory subjects
No prior maintencance therapy
No known transformation to acute leukemia
No prior BMT
No active AIHA

Key Eligibility Criteria Details

• Naïve to cytotoxic chemotherapy (endocrine or targeted therapy allowed)
• Scheduled to receive at least 4 repeated consecutive cycles with one of the following reference HEC (alone or in combination with other chemo agents) on Day 1
  • Cisplatin as single IV dose >70mg/m2
  • Cyclophosphamide >1500mg/m2
  • Carmustine (BCNU) >250 mg/m2
  • Dacarbazine (DTIC)
  • Mechloretamine (nitrogen mustard)
• ECOG PS 0-2
• Adequate laboratory values
• Cannot be scheduled to receive MEC or HEC on Day 2-5 of a cycle
• No active nausea of vomiting in 24 hours prior to chemo
• No symptomatic CNS disease
• No systemic steroids within 3 days of HEC
• No anti-emetic medicine within 24 hours of HEC

Key Eligibility Criteria Details

• Has undergone 1 allogeneic stem cell transplant from any type of donor and any donor source for hematologic disorder. Recipients of myeloablative and reduced-intesity conditioning regimens are eligible
• Clinically suspected Grade II to IV aGVHD per MAGIC criteria
• Evidence of myeloid engraftment
• Creatinine <2
• No more than 1 prior aHCT
• No more than 2 days of steroids for GVHD
• No presence of GVHD overlap syndrome
• No active HBV or HCV
• No known HIV
• No relapse of underlying malignancy post aHCT

Key Eligibility Criteria Details

Must have FGFR gene alteration as measured in CLIA-certified lab
None of the following malignancies:
Bladder cancer (urothelial)
Cholangiocarcinoma
Endometrial cancer
Glioblastoma multiforme (GBM)
Received at least 1 prior line of therapy
No standard therapy expected to result in durable remission
ECOG PS 0-1
No CNS disease
No acute/chronic pancreatitis
No impared cardiac function
No corneal or retinal disorder
No other cancer within 3 years
_

Key Eligibility Criteria Details

ALK or ROS1 mutation, trnaslocation, rearrangement, or amplification by CLIA-certified laboratory (IHC or FISH allowed)

May not have ALK+ lung cancer (butROS1 positive lung CA allowed)
Relapsed or progressive disease
ECOG PS 0-1
2nd line or higher
No standard therapy withdurable remission expected
No CNS disease

Key Eligibility Criteria Details

Any of the following molecular alterations
CDK4 amplification or mutation
CDK6 amplification or mutation
Cyclin D1 (CCND1) amplification
Cyclin D2 (CCND3) amplifcation
p16 (CDKN2A) mutationNone of the following malignancies:
ER/PR or HER2 positive breast cancer (TNBC only allowed)
Sarcoma (Eligible but cohort on hold)
Lung Cancer (Eligible but cohort on hold)
liposarcoma
prostate cancer
melanoma
teratoma
mantle cell lymphoma_
ECOG PS 0-1
No CNS involvement
At least one prior metastatic therapy
No expectation that further therapy will result in durable remission

Key Eligibility Criteria Details

None of the following malignancies:
NSCLC (non-small cell lung cancer)
CRC (colorectal cancer)
Melanoma
Pancreatic
Biliary
Low-grade serous ovarian
Mutation in any of the following:
RAF, RAS, NF1, MEK

Key Eligibility Criteria Details

Mutation or translocation of at least one of following genes:


FGFR 1/2/3, FLT3, cKIT,VEGFR 1/2, RET,
TrkA (NTRK1),PDGFRa/b,CSF-1R_
None of the following tumors:
Breast
RCC (kidney/renal)
Bladder
HCC (hepatocellular)
Endometrial
Squamous NSCLC
Heme malignancies (exceptFLT3 AML and MM)
At least one prior therapy for disease
ECOG 0-1
No brain mets
No anticoagulation

Key Eligibility Criteria Details

Newly diagnosed or refractory multiple myeloma
Measurable disease by either:
� Serum M protein
� Urine M protein
� qIgA (in IgA myeloma that can only be reliably measured this way)
ECOG PS 0-1
LVEF >40%
If prior tx with lenalidomide/dexamethasone must not have progressed within 3 months of starting therapy.
No Waldenstrom's macroglobulinemia or POEMS syndrome
No plasma cell leukemia, MDS, or amyloidosis
No prior tx with carfilzomib or oprozomib

Key Eligibility Criteria Details

• Relapsed/Refractory CLL or relapsed/refractory SLL with confirmed diagnosis per iwCLL 2008
• Active disease meeting at least 1 of the iwCLL 2008 criteria for requiring treatment
• Must have been previously treated for CLL or SLL with at least one prior regimen according to current guidelines
• Must have measurable nodal lesion(s) by CT
• ECOG PS
• ANC>or=1.0
• Plt>or=50
• AST/ALT
• No prior treatment with BTK or PI3K directed therapy
• No history of CNS lymphoma/leukemia
• No history of Richter's transformation or prolymphocytic leukemia
• No allo trx within 6 months, no auto trx within 3 months
• No malabsorption syndromes or other chronic GI disease
• No active HBV/HCV. No known HIV
• No other cancer within the lat 3 years (with few exceptions)
• No need for PPI therapy (must be stopped prior to study)

Key Eligibility Criteria Details

Confirmed CLL
ECOG 0-2
No intracranial involvement orprimary CNS lymphoma
No auto HCT within 3 months of entry
No allo HCT within 12 months

Key Eligibility Criteria Details

Previously treated ( at least 2 cycles)CLL/SLL
One or more high-risk cytogenetic features (del 17p, del 11q, p53 mutation)
Has at least one of following clinical criteria:
1.Progressive marrow failure (anemia or thrombocytopenia)
2.Massive, progressive, or symptomatic splenomegaly
3.Massive, progressive, or symptomatic lymphadenopathy
4.Progressive lymphocytosis as follows:
Either increase in ALC>50% over 2 months
or lymphocyte doubling time 30K)
5.Autoimmune anemia or thrombocytopenia
6.B-symptoms or unintentional weight loss
At least1 nodal lesion measuring>2 by>1 cm

ECOG PS 0-2
No prior allo HCT. Auto HCT only if at least 3 months prior.
No prior ibrutinib or other BTK inhibitor

Key Eligibility Criteria Details

Relapsed/refractory myeloma with at least 2 prior therapies
Measurable disease by M-protein, FLC, or plasmacytoma
ECOG PS 0-2
Acceptable renal, marrow, hepatic, cardiac fxn
No non-secretory disease
No POEMS syndrome or amyloidosis
No plasma cell leukemia or Waldenstroms
No symptomatic CNS disease
No recent high dose steroid use_