This study will evaluate the safety and clinical activity of MRTX849 (adagrasib) in combination with palbociclib in patients with advanced solid tumor malignancies with KRAS G12C mutation.

This study will evaluate the pharmacokinetics and preliminary clinical activity of MRTX849 (adagrasib) in combination with palbociclib in patients with advanced solid tumor malignancies with KRAS G12C mutation. MRTX849 is an orally available small molecule inhibitor of KRAS G12C and palbociclib is a small molecule inhibitor of CDK 4 and 6.

Inclusion Criteria:

• Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation
• Unresectable or metastatic disease.
• No available treatment with curative intent
• Adequate organ function

Exclusion Criteria:

• History of significant toxicity on prior KRAS G12C or CDK4/6 inhibitor therapies
• History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions likely to alter the absorption of study treatment or result in an inability to swallow
• Other active cancer
• Cardiac abnormalities