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

Inclusion Criteria:

• Histologically confirmed diagnosis of a solid tumor malignancy with any of thefollowing oncogenic mutations detected in tumor tissue or ctDNA by asponsor-approved test:

1. MRTX0902 monotherapy: known KRAS mutations, known annotated recurrentactivating SOS1, PTPN11, class III BRAF, or EGFR mutation, or known annotatedrecurrent 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 orpatient declines

• Presence of tumor lesions to be evaluated per RECIST 1.1. Phase 1 dose escalation,RECIST 1.1 measurable or evaluable disease

• Presence of a tumor lesion amenable to mandatory biopsy for pharmacodynamicevaluation at baseline and on-study unless Sponsor-confirmed as medically unsafe orinfeasible.

• 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 andadagrasib combination).

• History of significant hemoptysis or hemorrhage within 4 weeks of the first dose ofstudy 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 andproton pump inhibitors

• Cardiac abnormalities

• History of intestinal disease, inflammatory bowel disease, major gastric surgery, orother gastrointestinal conditions (eg, uncontrolled nausea, vomiting, malabsorptionsyndrome) likely to alter absorption of study treatment or result in inability toswallow oral medications