A Phase 1/2 Study of MRTX0902 in Solid Tumors With Mutations in the KRAS MAPK Pathway
- Conditions
- Non Small Cell Lung CancerAdvanced Solid TumorSolid TumorColo-rectal Cancer
- Interventions
- Registration Number
- NCT05578092
- Lead Sponsor
- Mirati Therapeutics Inc.
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 228
-
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:
- MRTX0902 monotherapy: known KRAS mutations, known annotated recurrent activating SOS1, PTPN11, class III BRAF, or EGFR mutation, or known annotated recurrent inactivating NF1 mutation;
- 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
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase 1/1B Combination Therapy MRTX849 Dose Escalation/Evaluation and Food Effect Assessment Phase 1/1B Combination Therapy MRTX0902 Dose Escalation/Evaluation and Food Effect Assessment Phase 2 MRTX0902 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 Phase 1/1B Monotherapy MRTX0902 Dose Escalation/Evaluation Phase 2 MRTX849 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
- Primary Outcome Measures
Name Time Method Phase 1: Number of Patients who Experience Dose-Limiting Toxicity 21 Days Phase 2: Progression free survival (PFS) 2 years Phase 2: Objective response rate (ORR) 2 years Phase 2: Overall survival (OS) 2 years Phase1/1B: Number of patients who experience a treatment-related adverse event Up to 2 years Phase 2: Duration of response (DOR) 2 years
- Secondary Outcome Measures
Name Time Method Area under the plasma concentration versus time curve Up to 4 days AUC - MRTX0902 and adagrasib
Time to achieve maximal plasma concentration Up to 4 days Tmax - MRTX0902 and adagrasib
Apparent total plasma clearance when dosed orally Up to 4 days CL/F - MRTX0902
Maximum observed plasma concentration Up to 4 days Cmax - MRTX0902 and adagrasib
Terminal elimination half-life Up to 4 days t1/2 - MRTX0902
Apparent volume of distribution when dosed orally Up to 4 days Vz/F - MRTX0902
Trial Locations
- Locations (24)
Fred Hutchinson Cancer Center
🇺🇸Seattle, Washington, United States
Local Institution - 001-120
🇺🇸Colorado Springs, Colorado, United States
Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
Local Institution - 1-13NVX8W8
🇺🇸Newark, Delaware, United States
Local Institution - 001-113
🇺🇸Washington, District of Columbia, United States
Sarah Cannon Research Institute at Florida Cancer Specialists
🇺🇸Orlando, Florida, United States
Local Institution - 001-118
🇺🇸Baltimore, Maryland, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
Local Institution - 001-125
🇺🇸Minneapolis, Minnesota, United States
Mayo Clinic - Cancer Center - Rochester - PPDS
🇺🇸Rochester, Minnesota, United States
Local Institution - 001-115
🇺🇸Hackensack, New Jersey, United States
Local Institution - 001-117
🇺🇸Bronx, New York, United States
University of Cincinnati Cancer Institute
🇺🇸Cincinnati, Ohio, United States
Local Institution - 001-109
🇺🇸Portland, Oregon, United States
Local Institution - 001-116
🇺🇸Pittsburgh, Pennsylvania, United States
Local Institution - 001-102
🇺🇸Nashville, Tennessee, United States
Sarah Cannon Research Institute Central Office
🇺🇸Nashville, Tennessee, United States
Local Institution - 001-121
🇺🇸Austin, Texas, United States
Local Institution - 001-112
🇺🇸Dallas, Texas, United States
Texas Oncology-Fort Worth Cancer Center
🇺🇸Fort Worth, Texas, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Local Institution - 001-123
🇺🇸Tyler, Texas, United States
NEXT Virginia
🇺🇸Fairfax, Virginia, United States
Pan American Center for Oncology Trials, LLC
🇵🇷Rio Piedras, Puerto Rico