The purpose of this study is to evaluate the safety and efficacy of a novel RAS(ON) inhibitor compared to standard(s) of care (SOC) treatment.

This is a global, randomized, open-label, Phase 3 study designed to evaluate whether treatment with RMC-6236 will improve progression free survival (PFS) or overall survival (OS) compared to Investigator's choice of standard of care chemotherapy in patients with metastatic PDAC who were previously treated with one prior line of therapy with 5-fluorouracil (5-FU) based or gemcitabine-based regimen.

Patients will be randomized in a 1:1 ratio to receive RMC-6236 (Arm A) or Investigator's choice of standard of care chemotherapy (Arm B).

Inclusion Criteria:

• At least 18 years old and has provided informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Histologically or cytologically confirmed PDAC with metastatic disease.
• Measurable disease per RECIST 1.1.
• Adequate organ function (bone marrow, liver, kidney, coagulation)
• Documented RAS mutation status, either mutant or wild-type. RAS mutations defined as nonsynonymous mutations in KRAS, NRAS, or HRAS at codons 12, 13, or 61 (G12, G13, or Q61).
• Able to take oral medications.

Exclusion Criteria:

• Prior therapy with direct RAS-targeted therapy (eg. degraders and/or inhibitors).
• History of or known central nervous system metastatic disease.
• Any conditions that may affect the ability to take or absorb study treatment
• Major surgery within 4 weeks prior to randomization.
• Patient is unable or unwilling to comply with protocol-required study visits or procedures