A Phase 1/2 Multiple Expansion Cohort Trial of MRTX1133 in Patients With Advanced Solid Tumors Harboring a KRAS G12D Mutation

This first-in-human clinical trial will begin with an exploration of MRTX1133 dose and regimen. 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 MRTX1133.

Inclusion Criteria:

• Histologically confirmed diagnosis of a solid tumor malignancy harboring KRAS G12D mutation in tumor tissue or ctDNA.
• Unresectable or metastatic disease.
• Patients must have received standard therapies appropriate for their tumor type and stage; first-line treatment for PDAC for certain cohorts.
• Presence of tumor lesions to be evaluated per RECIST v1.1:
  1. in the Phase 1 dose escalation cohorts, patients must have measurable or evaluable disease.
  2. in the Phase 1b and Phase 2 cohorts, patients must have measurable disease.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate organ function.
• Age ≥ 18 years

Exclusion Criteria:

• Active brain metastases or carcinomatous meningitis.
• Prior treatment with a KRAS G12D inhibitor (Phase 1b & Phase 2 only).
• History of significant hemoptysis or hemorrhage within 4 weeks of the first dose of study treatment.
• History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions likely to alter absorption of study treatment or result in inability to swallow oral medications.
• History of malignant small bowel obstruction.
• Cardiac abnormalities.