A Phase 1/1b Study of MPT-0118 as Monotherapy and in Combination With Pembrolizumab in Subjects With Advanced or Metastatic Refractory Solid Tumors
Trial Snapshot
- Phase
- Phase 1
- Sponsor
- Monopteros Therapeutics Inc.
- Enrollment
- 70
- Locations
- 5
- Primary Endpoint
- Part C: Number of subjects with TEAEs as assessed by NCI-CTCAE v5.0
Study Overview
Brief Summary
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
Detailed Description
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 Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Has a histologically- or cytologically-diagnosed solid tumor which is advanced or metastatic and which has progressed on or following at least one systemic therapy regimen administered for advanced or metastatic disease or for which no approved therapy exists. Subject's prior treatment should include all approved regimens that have demonstrated a survival advantage for the subject's disease, stage, and line of therapy.
- •Is aged ≥18 years at the time of signing the ICF
- •Has provided written informed consent
- •Has an ECOG Performance Status of 0 or 1
- •Has measurable disease per RECIST 1.1
- •Has an adequate tumor sample.
- •Has adequate liver, renal, hematologic, pulmonary, cardiac, and coagulation function.
- •Has a negative serum pregnancy test (for women of child-bearing potential) at Screening and a negative urine pregnancy test on Day 1 prior to the first dose of MPT 0118
- •Ability to swallow and retain and absorb oral medications in tablet or crushed form orally or via feeding tube (e.g., nasogastric feeding tube or percutaneous endoscopic gastrostomy feeding tube)
Exclusion Criteria
- •Has received cytotoxic chemotherapy, biologic agent, investigational agent, checkpoint inhibitors, or radiation therapy ≤3 weeks prior to the first dose of MPT-0118
- •Has received small-molecule kinase inhibitors or hormonal agents ≤14 days prior to the first dose of MPT-0118
- •Has been previously treated with a MALT1 inhibitor
- •Has clinically significant AEs that have not returned to baseline or ≤Grade 1 based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0
- •Has received systemic immunosuppressive agents within 14 days of the first dose of MPT-0118
- •Has undergone major surgery ≤6 weeks or minor surgery ≤14 days prior to the first dose of MPT-0118
- •Has clinically significant intercurrent disease
- •Part B and Part C: Has previously been treated with PD-1, PD-L1, or CTLA-4 inhibitors and required dose-interruption, permanent discontinuation, or systemic immunosuppression due to immune-related AEs
- •Has primary central nervous system (CNS) tumors or brain or leptomeningeal metastasis.
- •Has human immunodeficiency virus (HIV) infection
- •Has active hepatitis B or C infection
- •Women who are pregnant or breastfeeding
- •Has an unwillingness or inability to comply with procedures required in this protocol
- •Is currently receiving any other anticancer or investigational agent
Arms & Interventions
Part A:
Dose-escalation oral MPT-0118 BID
Intervention: MPT-0118 (Drug)
Part B:
Dose-escalation oral MPT-0118 BID + pembrolizumab (IV)
Intervention: MPT-0118 + pembrolizumab (Drug)
Part C:
Dose-expansion oral MPT-0118 BID + pembrolizumab (IV)
Intervention: MPT-0118 + pembrolizumab (Drug)
Outcomes
Primary Outcomes
Part C: Number of subjects with TEAEs as assessed by NCI-CTCAE v5.0
Time Frame: Through study completion, an average of 1 year
Incidence of TEAEs will be used to assess the safety of MPT-0118 + pembrolizumab
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 B: To determine the MTD or the RP2D of MPT-0118 + pembrolizumab
Time Frame: 1 cycle / 28 days
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.
Part A: To determine the MTD or the RP2D of MPT-0118
Time Frame: 1 cycle / 28 days
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.
Part C: Objective response rate (ORR) based on RECIST v1.1 and iRECIST
Time Frame: Through study completion, an average of 1 year
Secondary Outcomes
- Part A and B: ORR based on RECIST v 1.1 and iRECIST(Through study completion, an average of 1 year)
- Part A and B: DoR based on RECIST v 1.1 and iRECIST(Through study completion, an average of 1 year)
- Part A and B: PFS based on RECIST v 1.1 and iRECIST(Through study completion, an average of 1 year)
- Part C: Assessment of Overall Survival(Through study completion, an average of 1 year)
- Part A and B: Maximum plasma concentration of MPT-0118(1 cycle / 28 days)