This is an open-label, multi-center Phase 1 study of LY3410738, an oral, covalent isocitrate dehydrogenase (IDH) inhibitor, in patients with IDH1 and/or IDH2-mutant advanced hematologic malignancies who may have received standard therapy
This study includes 2 parts: dose escalation and dose expansion. The dose escalation will enroll eligible patients with select IDH-mutant advanced hematologic malignancies. Once the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of LY3410738 is established, the dose expansion will begin and enroll into 5 cohorts to further evaluate safety and clinical activity
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
260
Oral LY3410738
Oral venetoclax
Subcutaneous or intravenous azacitidine
To determine the maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D)
For Dose Escalation
Time frame: Up to 30 months
To assess the activity of LY3410738 as measured by the overall response rate (ORR) per the Investigator assessment
For Dose Expansion
Time frame: Up to 30 months
To determine the safety profile and tolerability of LY3410738 including acute and chronic toxicities by collecting and evaluating adverse events and treatment emergent adverse events
For Dose Escalation
Time frame: Up to 30 months
To characterize the pharmacokinetics (PK) properties of LY3410738 by collecting and evaluating serum at protocol specified time points
For Dose Escalation
Time frame: Up to 30 months
To characterize the pharmacodynamic properties of LY3410738 as expressed by change in 2-HG oncometabolite levels in plasma
For Dose Escalation
Time frame: Up to 30 months
To assess the activity of LY3410738 as measured by the overall response rate (ORR) per Investigator assessment
For Dose Escalation
Time frame: Up to 30 months
To assess the activity of LY3410738 as measured by Best Overall Response (BOR) per Investigator assessment
For Dose Expansion
Time frame: Up to 30 months
To assess the activity of LY3410738 by Complete Remission (CR) Rate (CRR) plus partial hematologic recovery (AML patients)
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City of Hope National Medical Center
Duarte, California, United States
UCLA Medical Center
Los Angeles, California, United States
University of California, Davis - Health Systems
Sacramento, California, United States
H Lee Moffitt Cancer Center
Tampa, Florida, United States
Northwestern University
Chicago, Illinois, United States
University of Chicago Hospital
Chicago, Illinois, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Roswell Park Cancer Institute
Buffalo, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States
...and 27 more locations
For Dose Expansion
Time frame: Up to 30 months
To assess the activity of LY3410738 by Duration of Response
For Dose Expansion
Time frame: Up to 30 months
To assess the activity of LY3410738 by Hematologic improvement in patients with MDS
For Dose Expansion
Time frame: Up to 30 months
To determine the safety profile and tolerability of LY3410738 including acute and chronic toxicities by collecting and evaluating Adverse events and treatment emergent adverse events
For Dose Expansion
Time frame: Up to 30 months
To characterize the pharmacokinetics (PK) properties of LY3410738 by collecting and evaluating serum at protocol specified time points
For Dose Expansion
Time frame: Up to 30 months
To characterize the pharmacodynamic properties of LY3410738 as expressed by change in 2-HG oncometabolite levels in plasma.
For Dose Expansion
Time frame: Up to 30 months