Phase 1/2 Study of MRTX1719 in Solid Tumors With MTAP Deletion

Study Overview
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Brief Summary
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This is a Phase 1/2, 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.

Detailed Description
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This first-in-human clinical trial will begin with an exploration of MRTX1719 dose and regimen. As potentially viable regimens are identified, Phase 1b expansion cohorts may be implemented to ensure sufficient safety experience, PK information, compare food effect and relative bioavailability between capsules and tablets, and early evidence of clinical activity are available to recommend Phase 2 regimens. In Phase 2, separate cohorts of patients by histological diagnosis and/or baseline characteristics will be evaluated for the clinical activity and efficacy of MRTX1719.

Official Title
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A Phase 1/2 Multiple Expansion Cohort Trial of MRTX1719 in Patients With Advanced Solid Tumors With Homozygous MTAP Deletion

Conditions
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Mesothelioma, Non Small Cell Lung Cancer, Malignant Peripheral Nerve Sheath Tumors, Solid Tumor, Pancreatic Adenocarcinoma, Advanced Solid Tumor

Intervention / Treatment
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* Drug: MRTX1719


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed diagnosis of a solid tumor malignancy with homozygous deletion of the MTAP gene detected in tumor tissue or ctDNA Unresectable or metastatic disease. Patients must have received standard therapies appropriate for their tumor type and stage with disease progression on or after the most recent treatment. Phase 1 dose escalation, RECIST 1.1 measurable or evaluable disease Phase 1b and Phase 2 cohorts, RECIST 1.1 measurable 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: 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

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1/1B<br>Dose Escalation/Evaluation | Drug: MRTX1719<br>* MRTX1719 is a potent PRMT5-MTA inhibitor<br>|
| Experimental: Phase 2<br>MRTX1719 RP2D administered to separate cohorts of patients with selected solid tumor malignancies with MTAP homozygous deletion to include the following: Mesothelioma, Pancreatic Adenocarcinoma, NSCLC, Malignant Peripheral Nerve Sheath Tumor, Other Solid Tumors | Drug: MRTX1719<br>* MRTX1719 is a potent PRMT5-MTA inhibitor<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1: Number of Patients who Experience Dose-Limiting Toxicity |  | 21 days | 
| Phase 1/1B: Number of patients who experience a treatment-related adverse event |  | Up to 2 years | 
| Phase 2: Objective response rate (ORR) |  | 2 years | 
| Phase 2: Duration of response (DOR) |  | 2 years | 
| Phase 2: Progression free survival (PFS) |  | 2 years | 
| Phase 2: Overall survival (OS) |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration versus time curve (AUC) |  | Up to 4 days | 
| Time to achieve maximal plasma concentration (Tmax) |  | Up to 4 days | 
| Maximum observed plasma concentration (Cmax) |  | Up to 4 days | 
| Terminal elimination half-life (t1/2) |  | Up to 4 days | 
| Apparent total plasma clearance when dosed orally (CL/F) |  | Up to 4 days | 
| Apparent volume of distribution when dosed orally (Vz/F) |  | Up to 4 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MTAP Deletion, Mesothelioma, Non Small Cell Lung Cancer, Malignant Peripheral Nerve Sheath Tumors, Solid Tumor, MTAP, Malignant, Pancreatic adenocarcinoma, Pancreas Cancer, PRMT5, Synthetic Lethality, Advanced Solid Tumor, NSCLC