A Phase 1 Multiple Expansion Cohort Trial of MRTX1719 in Patients With Advanced Solid Tumors With Homozygous MTAP Deletion

Trial Details

Sponsor: Bristol-Myers Squibb (industry)

Phase: 1

Start date: June 9, 2022

Planned enrollment: 320

Trial ID: NCT05245500

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More trial details at ClinicalTrials.gov

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Investigational Drug AI Analysis

Show for: BMS-986504 (MRTX1719)

HealthScout AI Analysis

Goal: The goal of this trial is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of MRTX1719 in patients with advanced solid tumors harboring homozygous MTAP gene deletion.

Patients: The study is enrolling adults with unresectable or metastatic solid tumors confirmed to have a homozygous MTAP deletion. Eligible patients must have tumors amenable to biopsy, ECOG performance status 0-1, and adequate organ function. Prior treatment with PRMT5 or MAT2A inhibitors is not allowed, and patients with active brain metastases, recent significant hemorrhage, or major gastrointestinal issues affecting drug absorption are excluded.

Design: This is an open-label, non-randomized, multicenter Phase 1 trial. It consists of an initial dose escalation of MRTX1719 followed by expansion cohorts to further characterize safety, pharmacokinetics, food effect, and early evidence of efficacy.

Treatments: The trial is studying MRTX1719, an investigational, selective PRMT5 inhibitor designed for cancers with MTAP gene deletion. The drug specifically targets the PRMT5-MTA complex, exploiting high methylthioadenosine (MTA) levels in MTAP-deleted cancers, providing selectivity for tumor over normal tissues. Early clinical data show objective responses across various MTAP-deleted tumor types, with reductions in tumor size and a favorable safety profile, including low rates of cytopenias and no observed dose-limiting toxicities up to 400mg daily. In the expansion phase, MRTX1719 may be combined with standard of care therapies in selected cohorts.

Outcomes: Primary endpoints are the incidence of dose-limiting toxicities, treatment-related adverse events, objective response rate, duration of response, progression-free survival, and overall survival. Pharmacokinetic parameters—including AUC, Tmax, Cmax, terminal half-life, clearance, and volume of distribution—are assessed as secondary endpoints.

Burden on patient: Patient burden is expected to be high. Participants must undergo mandatory tumor biopsies at baseline and on-study, as well as frequent blood draws for pharmacokinetic analyses, particularly in the dose escalation phase. This likely requires multiple clinic visits, additional monitoring, and possible travel to specialized centers. The trial’s intensive safety monitoring, typical for early-phase studies, adds to the overall burden compared to standard care.

Eligibility

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