RASolute 305: A Phase 3, Randomized, Double-blind, Placebo-controlled Study of Investigator Choice of Chemotherapy (Modified FOLFIRINOX or Gemcitabine Plus Nab-Paclitaxel) With or Without Zoldonrasib (RMC-9805) as First-line Treatment in Patients With Metastatic KRAS G12D-mutated Pancreatic Adenocarcinoma

Trial Details

Sponsor: Revolution Medicines, Inc. (industry)

Phase: 3

Start date: May 22, 2026

Planned enrollment: 670

Trial ID: NCT07621718

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More trial details at ClinicalTrials.gov

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Investigational Drug AI Analysis

Show for: Zoldonrasib (RM-036)

TrialFetch AI Analysis

Goal: Determine whether adding zoldonrasib to first-line chemotherapy improves progression-free or overall survival in metastatic KRAS G12D-mutated pancreatic adenocarcinoma.

Patients: Adults with recently diagnosed, previously untreated metastatic pancreatic adenocarcinoma harboring KRAS G12D, measurable disease, ECOG performance status 0–1, and adequate organ function. Prior systemic therapy for advanced or metastatic disease and prior RAS-targeted therapy are excluded.

Design: Global, randomized, double-blind, placebo-controlled trial comparing zoldonrasib plus chemotherapy with placebo plus chemotherapy. The investigator chooses the chemotherapy regimen.

Treatments: Both arms receive either modified FOLFIRINOX or gemcitabine plus nab-paclitaxel, standard first-line chemotherapy options; patients also receive oral zoldonrasib or matching placebo. Zoldonrasib is an investigational KRAS G12D inhibitor that forms a complex with cyclophilin A and irreversibly binds active, GTP-bound KRAS G12D to block downstream signaling. Preliminary first-line pancreatic cancer combination studies reported response rates of 82% with modified FOLFIRINOX (22 evaluable patients) and 61% with gemcitabine plus nab-paclitaxel (31 evaluable patients); these noncomparative results do not establish zoldonrasib’s contribution or a survival benefit.

Outcomes: Primary endpoints are investigator-assessed progression-free survival by RECIST v1.1 and overall survival. Secondary measures include centrally reviewed progression-free survival, response rate and duration, adverse events, laboratory and vital-sign changes, pancreatic pain, global quality of life, and zoldonrasib blood concentrations.

Burden on patient: Moderate. Patients receive multiagent intravenous chemotherapy plus an oral study drug or placebo, with ongoing visits for treatment, imaging, safety assessments, and questionnaires. Patients receiving zoldonrasib also have blood sampling for drug concentrations at selected visits through cycle 5 day 1. No mandatory research biopsy or imaging frequency is specified; much of the visit burden is likely associated with chemotherapy and routine disease monitoring.

Last updated: Sep 2026

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