A Phase 1/2 Study of MRTX0902 in Solid Tumors With Mutations in the KRAS MAPK Pathway

NCT ID: NCT05578092

Last Updated: 2025-09-30

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 228 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-12-02
• Study Completion Date: 2026-07-30

Brief Summary

This is a Phase 1/2, open-label, multicenter, study evaluating the safety, tolerability, PK, PD, and anti-tumor activity of MRTX0902 alone and in combination with MRTX849 (adagrasib) in patients with advanced solid tumor malignancy harboring mutations in the KRAS-MAPK pathways.

Detailed Description

This first-in-human clinical trial will begin with an exploration of MRTX0902 dose and regimen. Once safety experience and PK data are available for the monotherapy regimen, dose escalation of the combination of MRTX0902 and adagrasib will be initiated, and will include a separate preliminary food effect assessments on MRTX0902 PK in combination with adagrasib. As potentially viable regimens are identified, Phase 1b expansion cohorts may be implemented to ensure collection of sufficient safety and 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 MRTX0902 in combination with adagrasib.

Conditions

Solid Tumor; Advanced Solid Tumor; Non Small Cell Lung Cancer; Colo-rectal Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 1/1B Monotherapy

Dose Escalation/Evaluation

Group Type: EXPERIMENTAL

MRTX0902

Intervention Type: DRUG

SOS1 inhibitor

Phase 1/1B Combination Therapy

Dose Escalation/Evaluation and Food Effect Assessment

Group Type: EXPERIMENTAL

MRTX0902

Intervention Type: DRUG

SOS1 inhibitor

MRTX849

Intervention Type: DRUG

KRAS G12C inhibitor

Phase 2

MRTX0902 and adagrasib combination RP2D administered to separate cohorts of patients with selected solid tumor malignancies with KRAS G12C mutation to include the following: NSCLC, CRC, Other Solid Tumors

Group Type: EXPERIMENTAL

MRTX0902

Intervention Type: DRUG

SOS1 inhibitor

MRTX849

Intervention Type: DRUG

KRAS G12C inhibitor

Interventions

MRTX0902

SOS1 inhibitor

Intervention Type: DRUG

MRTX849

KRAS G12C inhibitor

Intervention Type: DRUG

Other Intervention Names

adagrasib (KRAZATI)

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed diagnosis of a solid tumor malignancy with any of the following oncogenic mutations detected in tumor tissue or ctDNA by a sponsor-approved test:

1. MRTX0902 monotherapy: known KRAS mutations, known annotated recurrent activating SOS1, PTPN11, class III BRAF, or EGFR mutation, or known annotated recurrent inactivating NF1 mutation;

2. MRTX0902 and adagrasib combination therapy: KRAS G12C mutation.

• Unresectable or metastatic disease
• No available treatment with curative intent; standard treatment is not available or patient declines
• Presence of tumor lesions to be evaluated per RECIST 1.1:

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.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate organ function

Exclusion Criteria

• Active brain metastases or carcinomatous meningitis
• Prior treatment with a KRAS G12C inhibitor (for Phase 1b expansion for MRTX0902 and adagrasib combination, and Phase 2 cohorts only)
• 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 pneumonitis or interstitial lung disease
• Ongoing need for medication with following characteristics: substrate of CYP3A; strong inducer or inhibitor or CYP3A and/or P-gp; strong inhibitors of BRCP and proton pump inhibitors
• Cardiac abnormalities
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mirati Therapeutics Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

Local Institution - 001-108

New Haven, Connecticut, United States

Local Institution - 001-119

Newark, Delaware, United States

Local Institution - 001-111

Orlando, Florida, United States

Local Institution - 001-103

Baltimore, Maryland, United States

Local Institution - 001-110

Rochester, Minnesota, United States

Local Institution - 001-115

Hackensack, New Jersey, United States

Local Institution - 001-106

Cincinnati, Ohio, United States

Local Institution - 001-109

Portland, Oregon, United States

Local Institution - 001-116

Pittsburgh, Pennsylvania, United States

Local Institution - 001-101

Nashville, Tennessee, United States

Local Institution - 001-102

Nashville, Tennessee, United States

Local Institution - 001-112

Dallas, Texas, United States

Local Institution - 001-122

Fort Worth, Texas, United States

Local Institution - 001-107

Houston, Texas, United States

Local Institution - 001-123

Tyler, Texas, United States

Local Institution - 001-104

Fairfax, Virginia, United States

Local Institution - 001-105

Seattle, Washington, United States

Local Institution - 001-114

Rio Piedras, , Puerto Rico

Countries

United States; Puerto Rico

Related Links

https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html

BMS Clinical Trial Information

https://www.bmsclinicaltrials.com/us/en/clinical-trials/NCT05578092.html

BMS Clinical Trial Patient Recruiting

Other Identifiers

CA247-0004

Identifier Type: OTHER

Identifier Source: secondary_id

0902-001

Identifier Type: OTHER

Identifier Source: secondary_id

CA247-0004

Identifier Type: -

Identifier Source: org_study_id