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

Study Identifier:
1719-001
CT.gov Identifier:
NCT05245500
EudraCT Identifier:
N/A
EU Trial (CTIS) Number:
N/A
Study Contact Information:
(210) 593-5651 or [email protected]
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Study Summary

This is a Phase 1, open-label, multicenter, study of the safety, tolerability, PK, PD, and anti-tumor activity of MRTX1719 patients with advanced, unresectable or metastatic solid tumor malignancy with homozygous deletion of the MTAP gene.

Symmetric dimethylarginine (SDMA) and intron retention are known PD BMs of PRMT5 inhibition. Therefore, PD effects of BMS-986504 were assessed via changes in plasma and tumor SDMA levels (mass spec and IHC), intron retention, and gene expression (RNASeq) based on samples collected at baseline (BL) and cycle 2 day 1 (C2D1). Additional analyses correlating efficacy outcomes with PD results and select mutations at BL were performed in clinically evaluable pts.

To report efficacy from the dose escalation and expansion phases in patients with NSCLC and safety in patients across multiple tumor types.

Efficacy was assessed in patients with NSCLC, and safety was assessed in enrolled patients across all tumors

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Non-Small Cell Lung Cancer
  • Pancreas
  • Solid Tumor
  • Mesothelioma
  • Bile Duct
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I
    Sex
    Female & Male
    Age
    18+ years
    Study Drug
    N/A
    Study Status
    Indicates the current recruitment status or the expanded access status
    Recruiting

    Requirements information
    Inclusion criteria
    • Inclusion Criteria
    • * Histologically confirmed diagnosis of a solid tumor malignancy with homozygous deletion of the MTAP gene detected in tumor tissue.
    • * Unresectable or metastatic disease.
    • * Presence of a tumor lesion amenable to mandatory biopsy for pharmacodynamic evaluation at baseline and on-study unless Sponsor-confirmed as medically unsafe or infeasible.
    • * Age ≥ 18 years.
    • * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
    • * Adequate organ function.
    Exclusion criteria
    • Exclusion Criteria
    • * Prior treatment with a PRMT5 or MAT2A inhibitor therapy.
    • * Active brain metastases or carcinomatous meningitis.
    • * History of significant hemoptysis or hemorrhage within 4 weeks of the first dose of study treatment.
    • * Major surgery within 4 weeks of first dose of study treatment.
    • * History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions (eg, uncontrolled nausea, vomiting, malabsorption syndrome) likely to alter absorption of study treatment or result in inability to swallow oral medications.
    • * Cardiac abnormalities.
    • * Other protocol-defined Inclusion/Exclusion criteria apply.
    • Exclusion criteria specific to the BMS-986504 with anti-PD-1 treatment substudy include lung radiation (> 30 Gy) within 6 months before the first treatment dose, active or prior documented autoimmune disease, immunosuppressant use within 28 days before the first treatment dose, history of primary immunodeficiency or allogeneic transplant, or receipt of a live vaccine within 30 days before the first treatment dose. Exclusion criteria specific to the PDAC substudy include a history of select lung diseases, connective tissue disorders, peripheral artery disease, chronic leukemias, or the ongoing need for warfarin or for a treatment known to inhibit or induce cytochrome P450 3A4 or 2C8 that cannot be switched to an alternative treatment prior to study entry.

    Clinical Study Information for Healthcare Providers

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START San Antonio
    San Antonio, TX, United States, 78229
    Investigator
    Kyriakos Papadopoulos
    Status
    Recruiting
    Condition(s) Treated at Site
    Non-Small Cell Lung Cancer
    Pancreas
    Solid Tumor
    Mesothelioma
    Bile Duct