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

Sponsor

Mirati Therapeutics Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05245500

Collaborator

(none)

339

Enrollment

Locations

Arms

Anticipated Duration (Months)

56.5

Patients Per Site

2.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Mesothelioma Non Small Cell Lung Cancer Malignant Peripheral Nerve Sheath Tumors Solid Tumor Pancreatic Adenocarcinoma Advanced Solid Tumor	Drug: MRTX1719	Phase 1/Phase 2

Detailed 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, 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

339 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 2, 2022

Anticipated Primary Completion Date :

Jan 31, 2024

Anticipated Study Completion Date :

Jan 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase 1/1B Dose Escalation/Evaluation	Drug: MRTX1719 MRTX1719 is a potent PRMT5-MTA inhibitor
Experimental: Phase 2 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 MRTX1719 is a potent PRMT5-MTA inhibitor

Arm

Intervention/Treatment

Experimental: Phase 1/1B

Dose Escalation/Evaluation

Drug: MRTX1719

MRTX1719 is a potent PRMT5-MTA inhibitor

Experimental: Phase 2

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

MRTX1719 is a potent PRMT5-MTA inhibitor

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 (Phase 2 only).
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sarah Cannon Research Institute at HealthONE	Denver	Colorado	United States	80218
2	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
3	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
4	Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
5	MD Anderson Cancer Center	Houston	Texas	United States	77030
6	START Center for Cancer Care	San Antonio	Texas	United States	78229