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

Solid Tumor Clinical Trial

Official title:

A Phase 1/2 Multiple Expansion Cohort Trial of the SOS1 Inhibitor MRTX0902 in Patients With Advanced Solid Tumors Harboring Mutations in the KRAS MAPK Pathway

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05578092
• Other study ID #: 0902-001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: November 4, 2022
• Est. completion date: July 30, 2026

Study information

• Verified date: March 2024
• 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 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 228
• Est. completion date: July 30, 2026
• Est. primary completion date: June 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 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

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Carcinoma, Non-Small-Cell Lung
• Colo-rectal Cancer
• Neoplasms
• Non Small Cell Lung Cancer
• Solid Tumor

Intervention

Drug:
• MRTX0902
SOS1 inhibitor
• MRTX849
KRAS G12C inhibitor

Locations

Country	Name	City	State
Puerto Rico	Pan America center for Oncology Trials LLC	Rio Piedras
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	Denver Drug Development Unit - HealthONE	Denver	Colorado
United States	NEXT Oncology Virginia	Fairfax	Virginia
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	SCRI - TN Oncology Nashville Drug Development Unit Clinic	Nashville	Tennessee
United States	Yale University, Yale Cancer Center	New Haven	Connecticut
United States	Oregon Health and Science University	Portland	Oregon
United States	Seattle Cancer Care Alliance	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Mirati Therapeutics Inc.

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1: Number of Patients who Experience Dose-Limiting Toxicity		21 Days
Primary	Phase1/1B: 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 - MRTX0902 and adagrasib	Up to 4 days
Secondary	Time to achieve maximal plasma concentration	Tmax - MRTX0902 and adagrasib	Up to 4 days
Secondary	Maximum observed plasma concentration	Cmax - MRTX0902 and adagrasib	Up to 4 days
Secondary	Terminal elimination half-life	t1/2 - MRTX0902	Up to 4 days
Secondary	Apparent total plasma clearance when dosed orally	CL/F - MRTX0902	Up to 4 days
Secondary	Apparent volume of distribution when dosed orally	Vz/F - MRTX0902	Up to 4 days