Study of MRTX1133 in Patients With Advanced Solid Tumors Harboring a KRAS G12D Mutation

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:
• in the Phase 1 dose escalation cohorts, patients must have measurable or evaluable disease.
• 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.