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

Mirati Therapeutics

Status and phase: Enrolling; Phase 2; Phase 1

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

Treatments: Drug: MRTX1719

Study type: Interventional

Funder types: Industry

Identifiers

NCT05245500

1719-001

CA240-0007

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 580 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.
• 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.
• Other protocol-defined Inclusion/Exclusion criteria apply.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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580 participants in 3 patient groups

Phase 1/1B

Experimental group

Description:

Dose Escalation/Evaluation

Treatment:

Drug: MRTX1719

Phase 2

Experimental group

Description:

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

Treatment:

Drug: MRTX1719

Phase 1b Sub-Study

Experimental group

Description:

MRTX1719 in combination with standard of care therapy in selected solid tumor malignancies with MTAP homozygous deletion

Treatment:

Drug: MRTX1719