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

Start Date13 Apr 2021

Sponsor / Collaborator

Monopteros Therapeutics, Inc.Startup

100 Clinical Results associated with MPT-0118

100 Translational Medicine associated with MPT-0118

100 Patents (Medical) associated with MPT-0118

Literatures (Medical) associated with MPT-0118

01 May 2023·Journal of immunotherapy and precision oncology

Translational Studies Using the MALT1 Inhibitor (S)-Mepazine to Induce Treg Fragility and Potentiate Immune Checkpoint Therapy in Cancer.

Article

Author: Fu, Amina ; Sun, Yi ; Keller, Peter ; Mazo, Irina ; Gao, Yun ; Litchfield, Kevin ; Grass, Carina ; Jenkins, Russell W ; Seeholzer, Thomas ; Kazer, Samuel W ; Mempel, Thorsten R ; von Andrian, Ulrich H ; Krappmann, Daniel ; Feederle, Regina ; Di Pilato, Mauro

IntroductionRegulatory T cells (Tregs) play a critical role in the maintenance of immune homeostasis but also protect tumors from immune-mediated growth control or rejection and pose a significant barrier to effective immunotherapy. Inhibition of MALT1 paracaspase activity can selectively reprogram immune-suppressive Tregs in the tumor microenvironment to adopt a proinflammatory fragile state, which offers an opportunity to impede tumor growth and enhance the efficacy of immune checkpoint therapy (ICT).MethodsWe performed preclinical studies with the orally available allosteric MALT1 inhibitor (S)-mepazine as a single-agent and in combination with anti-programmed cell death protein 1 (PD-1) ICT to investigate its pharmacokinetic properties and antitumor effects in several murine tumor models as well as patient-derived organotypic tumor spheroids (PDOTS).Results(S)-mepazine demonstrated significant antitumor effects and was synergistic with anti-PD-1 therapy in vivo and ex vivo but did not affect circulating Treg frequencies in healthy rats at effective doses. Pharmacokinetic profiling revealed favorable drug accumulation in tumors to concentrations that effectively blocked MALT1 activity, potentially explaining preferential effects on tumor-infiltrating over systemic Tregs.ConclusionsThe MALT1 inhibitor (S)-mepazine showed single-agent anticancer activity and presents a promising opportunity for combination with PD-1 pathway-targeted ICT. Activity in syngeneic tumor models and human PDOTS was likely mediated by induction of tumor-associated Treg fragility. This translational study supports ongoing clinical investigations (ClinicalTrials.gov Identifier: NCT04859777) of MPT-0118, (S)-mepazine succinate, in patients with advanced or metastatic treatment-refractory solid tumors.

100 Deals associated with MPT-0118

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced cancer	Phase 1	US	Monopteros Therapeutics, Inc.Startup	13 Apr 2021
Advanced Malignant Solid Neoplasm	Phase 1	US	Monopteros Therapeutics, Inc.Startup	13 Apr 2021
Refractory Cancer	Phase 1	US	Monopteros Therapeutics, Inc.Startup	13 Apr 2021
B-Cell Lymphoma	Phase 1	DE	Helmholtz Zentrum München Deutsches Forschungszentrum	05 Apr 2021

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