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 G12Dmutation in tumor tissue or ctDNA.

• Unresectable or metastatic disease.

• Patients must have received standard therapies appropriate for their tumor type andstage; 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 orevaluable 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 ofstudy treatment.

• History of intestinal disease, inflammatory bowel disease, major gastric surgery, orother gastrointestinal conditions likely to alter absorption of study treatment orresult in inability to swallow oral medications.

• History of malignant small bowel obstruction.

• Cardiac abnormalities.