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.