This is a Phase 1/1b open-label, dose-escalation, and cohort expansion study with BID (tablet) oral dose of MPT-0118 in subjects with advanced or metastatic refractory solid tumors. The study will be conducted in 3 parts: * Part A: MPT-0118 dose-escalation * Part B: MPT-0118 dose-escalation in combination with pembrolizumab * Part C: Cohort expansion of MPT-0118 in combination with pembrolizumab
MPT-0118 will be administered orally twice daily (BID). Pembrolizumab will be administered intravenously (IV) at a dose of 200 mg every 3 weeks.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
70
MPT-0118 is an inhibitor of MALT1 protease
MPT-0118 is an inhibitor of MALT1 protease; pembrolizumab is a PD-1 inhibitor
St. John's Cancer Center
Santa Monica, California, United States
RECRUITINGMassachusetts General Hospital
Boston, Massachusetts, United States
RECRUITINGColumbia University
New York, New York, United States
RECRUITINGMD Anderson Cancer Center
Houston, Texas, United States
RECRUITINGNEXT Oncology
San Antonio, Texas, United States
RECRUITINGPart A: To determine the MTD or the RP2D of MPT-0118
The incidence and severity of treatment-emergent adverse events (TEAEs) qualifying as protocol-defined DLTs in Cycle 1 will guide the establishment of the protocol-defined RP2D and/or MTD.
Time frame: 1 cycle / 28 days
Part B: To determine the MTD or the RP2D of MPT-0118 + pembrolizumab
The incidence and severity of TEAEs qualifying as protocol-defined DLTs in Cycle 1 will guide the establishment of the protocol-defined RP2D and/or MTD.
Time frame: 1 cycle / 28 days
Part C: Number of subjects with TEAEs as assessed by NCI-CTCAE v5.0
Incidence of TEAEs will be used to assess the safety of MPT-0118 + pembrolizumab
Time frame: Through study completion, an average of 1 year
Part C: Objective response rate (ORR) based on RECIST v1.1 and iRECIST
Time frame: Through study completion, an average of 1 year
Part C: Duration of response (DoR) based on RECIST v1.1 and iRECIST
Time frame: Through study completion, an average of 1 year
Part C: Progression-free survival (PFS) based on RECIST v1.1 and iRECIST
Time frame: Through study completion, an average of 1 year
Part A and B: Maximum plasma concentration of MPT-0118
Time frame: 1 cycle / 28 days
Part A and B: ORR based on RECIST v 1.1 and iRECIST
Time frame: Through study completion, an average of 1 year
Part A and B: DoR based on RECIST v 1.1 and iRECIST
Time frame: Through study completion, an average of 1 year
Part A and B: PFS based on RECIST v 1.1 and iRECIST
Time frame: Through study completion, an average of 1 year
Part C: Assessment of Overall Survival
Time frame: Through study completion, an average of 1 year
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