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

Mirati Therapeutics

Status and phase: Active, not recruiting; Phase 2; Phase 1

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

Treatments: Drug: MRTX0902; Drug: MRTX849

Study type: Interventional

Funder types: Industry

Identifiers

NCT05578092

CA247-0004

0902-001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 228 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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228 participants in 3 patient groups

Phase 1/1B Monotherapy

Experimental group

Description:

Dose Escalation/Evaluation

Treatment:

Drug: MRTX0902

Phase 1/1B Combination Therapy

Experimental group

Description:

Dose Escalation/Evaluation and Food Effect Assessment

Treatment:

Drug: MRTX849

Drug: MRTX0902

Phase 2

Experimental group

Description:

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

Treatment:

Drug: MRTX849

Drug: MRTX0902