Study of Zoldonrasib + Chemo of Investigator's Choice vs Placebo + Chemo of Investigator's Choice as First-line Treatment in Metastatic KRAS G12D-mutated Pancreatic Adenocarcinoma ( RASolute 305 )

This is a Phase 3, global, randomized, double-blind study designed to evaluate whether treatment with zoldonrasib in combination with Investigator choice of chemotherapy will improve progression-free survival or overall survival compared to placebo in combination with Investigator choice of chemotherapy when given to patients with previously untreated, 1L metastatic KRAS G12D-mutated pancreatic adenocarcinoma. Choice of chemotherapy (mFFX or GnP) will be at the discretion of the Investigator.

Patients will be randomized to one of two arms: zoldonrasib + Investigator choice of chemotherapy (Arm A) or placebo + Investigator choice of 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 pancreatic adenocarcinoma.
• Diagnosis of metastatic disease ≤ 6 weeks prior to screening.
• Documented KRAS G12D mutation status.
• Measurable disease per RECIST v1.1.
• Adequate organ function (bone marrow, liver, kidney, coagulation).
• Able to take oral medications.

Exclusion criteria

• Prior treatment with systemic anticancer therapy in unresectable locally advanced or metastatic setting.
• Prior systemic RAS-targeted therapy any time prior to randomization.
• Presence of other known driver mutations with approved targeted therapies
• Active or known history of untreated central nervous system metastatic disease.
• Any conditions that may affect the ability to take or absorb study drug.
• Major surgery within 28 days prior to randomization.
• Patient is unable or unwilling to comply with protocol-required study visits or procedures.