A Study of ERAS-007 in Patients With Advanced Gastrointestinal Malignancies

Inclusion Criteria: * Age ≥ 18 years. * Willing and able to give written informed consent. * Have histologically or cytologically confirmed metastatic CRC harboring applicable mutation(s) (e.g., BRAF V600E; KRAS or NRAS mutations) or metastatic PDAC harboring KRAS mutation based on an analytically validated assay performed on tumor tissue in a certified testing laboratory. * Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. * Adequate bone marrow and organ function. * Have ECOG performance status of 0 or 1. * Willing to comply with all protocol-required visits, assessments, and procedures. * Able to swallow oral medication. Exclusion Criteria: * Prior therapy with a RAS, MEK, or ERK inhibitor. Depending on which treatment arm the patient is assigned, other therapies could also be prohibitive. * Anti-cancer therapy ≤ 21 days or 4 half-lives prior to first dose of study drug, whichever is shorter. * Palliative radiation ≤ 7 days prior to first dose of study drug. * Symptomatic brain metastasis or leptomeningeal disease. * Gastrointestinal conditions that may affect absorption of oral medications * Active infection requiring systemic therapy, or a known history of HIV infection, hepatitis B virus, or hepatitis C virus. * History of chronic inflammatory bowel disease or Crohn's disease requiring medical intervention (immunomodulatory or immunosuppressive medications or surgery) ≤ 12 months prior to first study drug dose. * Active, clinically significant interstitial lung disease or pneumonitis. * Impaired cardiovascular function or clinically significant cardiovascular disease. * History of thromboembolic or cerebrovascular events ≤ 6 months prior to first dose. * Major surgery within 28 days of enrollment, or anticipation of major surgery during study treatment. * Known intolerance or contraindication to encorafenib, cetuximab, or palbociclib. * Pregnant or breastfeeding women. * Any evidence of severe or uncontrolled systemic disease or evidence of any other significant clinical disorder or laboratory finding that renders the patient inappropriate to participate in the study.