Advanced Cancer, Advanced Solid Tumor, Metastatic Cancer, Refractory Cancer, Solid Tumor, Adult
Conditions
Keywords
MALT1 inhibitor
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.
Interventions
DRUGMPT-0118 + pembrolizumab
MPT-0118 is an inhibitor of MALT1 protease; pembrolizumab is a PD-1 inhibitor
DRUGMPT-0118
MPT-0118 is an inhibitor of MALT1 protease
Sponsors
Monopteros Therapeutics Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Part A: Each dose-escalation cohort will initially recruit single-subject cohorts until a subject has a Grade 2 or greater adverse event (AE) during the DLT period considered at least possibly related to MPT-0118, at which time 2 additional subjects will be enrolled in that cohort, and a 3 + 3 design will subsequently be utilized. Part B: Each dose-escalation cohort will initially recruit 3 patients to receive MPT-0118 + pembrolizumab in a standard 3+3 design; the cohort will be expanded in the event of a DLT. Part C: Once the RP2D has been established for MPT-0118 monotherapy and combination therapy with MPT-0118 + pembrolizumab, expansion cohorts will be enrolled to further evaluate combination therapy.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. 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. 2. Is aged ≥18 years at the time of signing the ICF 3. Has provided written informed consent 4. Has an ECOG Performance Status of 0 or 1 5. Has measurable disease per RECIST 1.1 6. Has an adequate tumor sample. 7. Has adequate liver, renal, hematologic, pulmonary, cardiac, and coagulation function. 8. 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 9. 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) Key
Exclusion criteria
1. Has received cytotoxic chemotherapy, biologic agent, investigational agent, checkpoint inhibitors, or radiation therapy ≤3 weeks prior to the first dose of MPT-0118 2. Has received small-molecule kinase inhibitors or hormonal agents ≤14 days prior to the first dose of MPT-0118 3. Has been previously treated with a MALT1 inhibitor 4. 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 5. Has received systemic immunosuppressive agents within 14 days of the first dose of MPT-0118 6. Has undergone major surgery ≤6 weeks or minor surgery ≤14 days prior to the first dose of MPT-0118 7. Has clinically significant intercurrent disease 8. 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 9. Has primary central nervous system (CNS) tumors or brain or leptomeningeal metastasis. 10. Has human immunodeficiency virus (HIV) infection 11. Has active hepatitis B or C infection 12. Women who are pregnant or breastfeeding 13. Has an unwillingness or inability to comply with procedures required in this protocol 14. Is currently receiving any other anticancer or investigational agent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part C: Progression-free survival (PFS) based on RECIST v1.1 and iRECIST | Through study completion, an average of 1 year | — |
| Part A: To determine the MTD or the RP2D of MPT-0118 | 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 B: To determine the MTD or the RP2D of MPT-0118 + pembrolizumab | 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 C: Number of subjects with TEAEs as assessed by NCI-CTCAE v5.0 | Through study completion, an average of 1 year | Incidence of TEAEs will be used to assess the safety of MPT-0118 + pembrolizumab |
| Part C: Objective response rate (ORR) based on RECIST v1.1 and iRECIST | Through study completion, an average of 1 year | — |
| Part C: Duration of response (DoR) based on RECIST v1.1 and iRECIST | Through study completion, an average of 1 year | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
Countries
United States
Contacts
Primary ContactPeter Keller
Outcome results
None listed