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.