1035TiP - A phase I/Ib study of MPT-0118 as monotherapy and in combination with pembrolizumab in subjects with advanced or metastatic solid tumors

Background

MPT-0118 is an inhibitor of mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) protease developed by Monopteros Therapeutics for the treatment of solid tumors. Despite the transforming effects of immune checkpoint therapy (ICT), objective response rates are still low in solid tumors. In the tumor microenvironment (TME), regulatory T-cells (T_reg) are unstable and can be reprogrammed to lose their immunosuppressive function and secrete interferon-γ, offering a strategy to sensitize unresponsive tumors to ICT. Blockade of MALT1 protease by MPT-0118 induces T_reg reprogramming in the TME without affecting T_reg in healthy tissue, which allows for cytotoxic T-lymphocyte-mediated tumor lysis and recruitment of new tumor-infiltrating lymphocytes. The increased inflammation caused by these effects then increases programmed death-ligand 1 expression allowing synergy between MPT-0118 and pembrolizumab.

Trial design

Monopteros Therapeutics is conducting a first-in-human, phase 1/1b open-label, multicenter, dose-escalation, safety, pharmacokinetics, and biomarker study of MPT-0118 as monotherapy and in combination with pembrolizumab in approximately 70 adults with advanced/metastatic refractory solid tumors. The study will be conducted in 3 parts: Part A: MPT-0118 monotherapy with 3+3 dose-escalation Part B: MPT-0118 in combination with standard dose of pembrolizumab with 3+3 dose-escalation Part C: Cohort expansion of MPT-0118 and pembrolizumab combination at the recommended phase 2 dose (RP2D) MPT-0118 will be administered orally twice daily to subjects in each part of the study, and pembrolizumab will be administered intravenously to subjects in Parts B, and C. Subjects will receive treatment in 3- or 4-week cycles and may continue on the study as long as they are tolerating treatment without disease progression. The primary objectives of Parts A and B are to determine the safety and tolerability, maximum tolerated dose, dose limiting toxicities, and RP2D of MPT-0118 as monotherapy and in combination. The primary objectives of Part C are to confirm safety in combination and to evaluate the preliminary anti-tumor activity.

Clinical trial identification

NCT04859777.

Editorial acknowledgement

Legal entity responsible for the study

Monopteros Therapeutics Inc.

Funding

Monopteros Therapeutics Inc.

Disclosure

E.A. Lim: Financial Interests, Stocks/Shares: Pfizer. A. Pande: Financial Interests, Personal, Advisory Role: Monopteros Therapeutics; Financial Interests, Member of the Board of Directors: Sio Gene Therapie; Financial Interests, Member of the Board of Directors: Karuna Therapeutics; Financial Interests, Member of the Board of Directors: Immunovant; Financial Interests, Member of the Board of Directors: Autifony Therapeutics; Financial Interests, Member of the Board of Directors: Perception Neurosciences; Financial Interests, Advisory Role: MAPS Public Benefit Corporation; Financial Interests, Advisory Role: MMS Holdings; Financial Interests, Advisory Role: Datavant; Financial Interests, Advisory Role: PureTech Health; Financial Interests, Advisory Role: Avanir Pharmaceuticals. P. Keller: Financial Interests, Personal, Full or part-time Employment: Monopteros Therapeutics; Financial Interests, Personal, Leadership Role: Divide and Conquer. All other authors have declared no conflicts of interest.