Phase 3 Study of Investigator Choice of Chemotherapy with or without Zoldonrasib as First-line Treatment in Metastatic KRAS G12D-mutated Pancreatic Adenocarcinoma

INTERVENTION: Product Name: RMC‐9805, Product Code:PRD12324715, Pharmaceutical Form: TABLET, Other descriptive name: , Strength: , Product Name: RMC‐9805 Matching Placebo, Product Code:N/A, Pharmaceutical Form: N/A, Other descriptive name: N/A , Strength: , Pharmaceutical form of the placebo: N/A CONDITION: Pancreatic Adenocarcinoma ; MedDRA version: 21.1Level: LLTClassification code: 10051971Term: Pancreatic adenocarcinoma Class: 10029104 Therapeutic area: Diseases [C] ‐ Neoplasms [C04] PRIMARY OUTCOME: Main Objective: To compare the efficacy of zoldonrasib plus Investigator choice of chemotherapy (mFFX or GnP) versus placebo plus Investigator choice of chemotherapy (mFFX or GnP) Primary end point(s): PFS, defined as the time from randomization until disease progression or death from any cause, whichever occurs first. Progression is assessed per RECIST v1.1 by Investigator, OS, defined as the time from randomization until death from any cause Secondary Objective: To compare additional measures of efficacy of treatment with zoldonrasib plus Investigator choice of chemotherapy (mFFX or GnP) versus placebo plus Investigator choice of chemotherapy (mFFX or GnP), To assess the safety and tolerability of zoldonrasib plus Investigator choice of chemotherapy (mFFX or GnP) versus placebo plus Investigator choice of chemotherapy (mFFX or GnP), To compare the effect on HRQoL of treatment with zoldonrasib plus Investigator choice of chemotherapy (mFFX or GnP) versus placebo plus Investigator choice of chemotherapy (mFFX or GnP), To characterize the PK of zoldonrasib plus Investigator choice of chemotherapy (mFFX or GnP) SECONDARY OUTCOME: Secondary end point(s):Change from baseline on the EORTC‐QLQ‐C30 global health status score Secondary end point(s):Change from baseline on the EORTC‐QLQ‐PAN26 pain scale Secondary end point(s):Clinically significant changes in laboratory test values and vital signs Secondary end point(s):DOR, defined as the time from first evidence of objective response (PR or CR) per RECIST v1.1 to disease progression or death due to any cause, whichever occurs first, as assessed by Investigator and BICR Secondary end point(s):Incidence and severity of TEAEs, TRAEs, and SAEs Secondary end point(s):Objective response of PR or CR per RECIST v1.1, as assessed by Investigator and BICR Secondary end point(s):PFS, defined as the time from randomization until disease progression or death from any cause, whichever occurs first. Progression is assessed per RECIST v1.1 by BICR Secondary end point(s):Predose and postdose blood concentrations of zoldonrasib INCLUSION CRITERIA: Adult patients (=18 years or legal age of consent), Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, Histologically of cytologically confirmed pancreatic adenocarcinoma, Metastatic disease, newly diagnosed within =6 weeks prior to screening, Documented KRAS G12D mutations identified by a validated assay, At least one measurable lesion per RECIST version 1.1, Adequate organ function (hematologic, hepatic and renal), Able to take oral medications