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

Solid Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05245500
• Other study ID #: 1719-001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: June 2, 2022
• Est. completion date: April 30, 2026

Study information

• Verified date: October 2023
• Source: Mirati Therapeutics Inc.
• Contact: Mirati Therapeutics Study Locator Services
• Phone: 1-844-893-5530
• Email: miratistudylocator[@]careboxhealth.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 370
• Est. completion date: April 30, 2026
• Est. primary completion date: April 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

1. Phase 1 dose escalation, RECIST 1.1 measurable or evaluable disease

2. 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

Related Conditions & MeSH terms

• Adenocarcinoma
• Advanced Solid Tumor
• Carcinoma, Non-Small-Cell Lung
• Malignant Peripheral Nerve Sheath Tumors
• Mesothelioma
• Mesothelioma, Malignant
• Neoplasms
• Nerve Sheath Neoplasms
• Non Small Cell Lung Cancer
• Pancreatic Adenocarcinoma
• Solid Tumor

Intervention

Drug:
• MRTX1719
MRTX1719 is a potent PRMT5-MTA inhibitor

Locations

Country	Name	City	State
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Sarah Cannon Research Institute at HealthONE	Denver	Colorado
United States	NEXT Virginia	Fairfax	Virginia
United States	MD Anderson Cancer Center	Houston	Texas
United States	Oncology Consultants, P.A.	Houston	Texas
United States	Mayo Clinic	Jacksonville	Florida
United States	Froedtert Hospital & the Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Sarah Cannon Research Institute at Florida Cancer Specialists	Orlando	Florida
United States	Mayo Clinic	Phoenix	Arizona
United States	NorthShore Hematology Oncology Associates P.C New York Cancer and Blood Specialists	Port Jefferson Station	New York
United States	Mayo Clinic	Rochester	Minnesota
United States	START Center for Cancer Care	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Mirati Therapeutics Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1: Number of Patients who Experience Dose-Limiting Toxicity		21 days
Primary	Phase 1/1B: Number of patients who experience a treatment-related adverse event		Up to 2 years
Primary	Phase 2: Objective response rate (ORR)		2 years
Primary	Phase 2: Duration of response (DOR)		2 years
Primary	Phase 2: Progression free survival (PFS)		2 years
Primary	Phase 2: Overall survival (OS)		2 years
Secondary	Area under the plasma concentration versus time curve (AUC)		Up to 4 days
Secondary	Time to achieve maximal plasma concentration (Tmax)		Up to 4 days
Secondary	Maximum observed plasma concentration (Cmax)		Up to 4 days
Secondary	Terminal elimination half-life (t1/2)		Up to 4 days
Secondary	Apparent total plasma clearance when dosed orally (CL/F)		Up to 4 days
Secondary	Apparent volume of distribution when dosed orally (Vz/F)		Up to 4 days