A Study of MPT-0118 in Subjects With Advanced or Metastatic Refractory Solid Tumors

Study Overview
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Brief Summary
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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
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MPT-0118 will be administered orally twice daily (BID). Pembrolizumab will be administered intravenously (IV) at a dose of 200 mg every 3 weeks.

Official Title
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A Phase 1/1b Study of MPT-0118 as Monotherapy and in Combination With Pembrolizumab in Subjects With Advanced or Metastatic Refractory Solid Tumors

Conditions
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Solid Tumor, Adult, Advanced Solid Tumor, Advanced Cancer, Metastatic Cancer, Refractory Cancer

Intervention / Treatment
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* Drug: MPT-0118
* Drug: MPT-0118 + pembrolizumab


Participation Criteria
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Eligibility Criteria
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Key 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) Key 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A:<br>Dose-escalation oral MPT-0118 BID | Drug: MPT-0118<br>* MPT-0118 is an inhibitor of MALT1 protease<br>|
| Experimental: Part B:<br>Dose-escalation oral MPT-0118 BID + pembrolizumab (IV) | Drug: MPT-0118 + pembrolizumab<br>* MPT-0118 is an inhibitor of MALT1 protease; pembrolizumab is a PD-1 inhibitor<br>|
| Experimental: Part C:<br>Dose-expansion oral MPT-0118 BID + pembrolizumab (IV) | Drug: MPT-0118 + pembrolizumab<br>* MPT-0118 is an inhibitor of MALT1 protease; pembrolizumab is a PD-1 inhibitor<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 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. | 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. | 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 | Through study completion, an average of 1 year | 
| 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 | 
| Part C: Progression-free survival (PFS) based on RECIST v1.1 and iRECIST |  | Through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A and B: Maximum plasma concentration of MPT-0118 |  | 1 cycle / 28 days | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MALT1 inhibitor