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

A Phase 1 Multiple Expansion Cohort Trial of the SOS1 Inhibitor MRTX0902 in Patients With Advanced Solid Tumors Harboring Mutations in the KRAS MAPK Pathway

This is a Phase 1, 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.

Study Overview

• Status: Terminated
• Conditions: Solid Tumor; Non Small Cell Lung Cancer; Advanced Solid Tumor; Colo-rectal Cancer
• Intervention / Treatment: Drug: MRTX849; Drug: MRTX0902

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.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 1

Contacts and Locations

Study Locations

• Puerto Rico
  • Rio Piedras, Puerto Rico, 00935
    • Local Institution - 001-114
• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Local Institution - 001-108
  • Delaware
    • Newark, Delaware, United States, 19713-2055
      • Local Institution - 001-119
  • Florida
    • Orlando, Florida, United States, 32827-7400
      • Local Institution - 001-111
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Local Institution - 001-103
  • Minnesota
    • Rochester, Minnesota, United States, 55905-0001
      • Local Institution - 001-110
  • New Jersey
    • Hackensack, New Jersey, United States, 07601-2191
      • Local Institution - 001-115
  • Ohio
    • Cincinnati, Ohio, United States, 45219-2364
      • Local Institution - 001-106
  • Oregon
    • Portland, Oregon, United States, 97239-3011
      • Local Institution - 001-109
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • Local Institution - 001-116
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Local Institution - 001-101
    • Nashville, Tennessee, United States, 37203
      • Local Institution - 001-102
  • Texas
    • Dallas, Texas, United States, 75246-2003
      • Local Institution - 001-112
    • Fort Worth, Texas, United States, 76104-2154
      • Local Institution - 001-122
    • Houston, Texas, United States, 77030
      • Local Institution - 001-107
    • Tyler, Texas, United States, 75708-3154
      • Local Institution - 001-123
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Local Institution - 001-104
  • Washington
    • Seattle, Washington, United States, 98109
      • Local Institution - 001-105

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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. Phase 1 dose escalation, RECIST 1.1 measurable or evaluable 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).
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1/1B Monotherapy; Dose Escalation/Evaluation	Drug: MRTX0902; SOS1 inhibitor
Experimental: Phase 1/1B Combination Therapy; Dose Escalation/Evaluation and Food Effect Assessment	Drug: MRTX849; KRAS G12C inhibitor; Other Names: adagrasib (KRAZATI); Drug: MRTX0902; SOS1 inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of patients who experience a treatment-related adverse event	Up to 2 years
Number of Patients who Experience Dose-Limiting Toxicity	21 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the plasma concentration versus time curve	AUC - MRTX0902 and adagrasib	Up to 4 days
Time to achieve maximal plasma concentration	Tmax - MRTX0902 and adagrasib	Up to 4 days
Maximum observed plasma concentration	Cmax - MRTX0902 and adagrasib	Up to 4 days
Terminal elimination half-life	t1/2 - MRTX0902	Up to 4 days
Apparent total plasma clearance when dosed orally	CL/F - MRTX0902	Up to 4 days
Apparent volume of distribution when dosed orally	Vz/F - MRTX0902	Up to 4 days

Collaborators and Investigators

• Sponsor: Mirati Therapeutics Inc.
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2022
• Primary Completion (Actual): February 3, 2026
• Study Completion (Actual): February 3, 2026

Study Registration Dates

• First Submitted: October 10, 2022
• First Submitted That Met QC Criteria: October 10, 2022
• First Posted (Actual): October 13, 2022

Study Record Updates

• Last Update Posted (Actual): February 19, 2026
• Last Update Submitted That Met QC Criteria: February 16, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: NSCLC; Non Small Cell Lung Cancer; EGFR; Colorectal Cancer; Malignant; Solid Tumor; Advanced Solid Tumor; KRAS; CRC; SOS1
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Respiratory Tract Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Colonic Diseases; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Colorectal Neoplasms; Colonic Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents; adagrasib
• Other Study ID Numbers: CA247-0004 (Other Identifier: Bristol-Myers Squibb Protocol ID); 0902-001 (Other Identifier: Mirati Therapeutics Protocol ID)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No