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: To determine whether adding zoldonrasib to first-line chemotherapy improves progression-free survival or overall survival compared with chemotherapy plus placebo in metastatic KRAS G12D-mutated pancreatic adenocarcinoma.

Patients: Adults with histologically or cytologically confirmed pancreatic adenocarcinoma, metastatic disease diagnosed within 6 weeks before screening, a documented KRAS G12D mutation, measurable disease by RECIST v1.1, ECOG performance status 0–1, and adequate organ function. Patients must not have received systemic anticancer therapy for unresectable locally advanced or metastatic disease or prior systemic RAS-targeted therapy. Key exclusions include another actionable driver alteration, active or untreated CNS metastases, impaired oral drug absorption, and major surgery within 28 days before randomization.

Design: Global, randomized, double-blind, placebo-controlled, first-line study. Patients are assigned to zoldonrasib or matching placebo, each combined with the investigator’s choice of modified FOLFIRINOX or gemcitabine plus nab-paclitaxel. Efficacy and safety follow-up may continue for approximately 4 years.

Treatments: The experimental arm receives oral zoldonrasib plus either modified FOLFIRINOX—oxaliplatin, leucovorin, fluorouracil, and irinotecan—or gemcitabine plus nab-paclitaxel. The control arm receives placebo with the same investigator-selected chemotherapy options, both of which are established first-line regimens for metastatic pancreatic adenocarcinoma. Zoldonrasib is an investigational mutant-selective KRAS G12D(ON) inhibitor that forms a tri-complex with cyclophilin A and covalently binds active, GTP-bound KRAS G12D, thereby suppressing downstream RAS signaling. Early, nonrandomized data in previously treated KRAS G12D-mutated pancreatic cancer reported a 30% objective response rate and 80% disease control rate at 1200 mg/day; these company-reported findings remain preliminary and do not establish benefit in the first-line combination setting. Early solid-tumor safety data identified mainly gastrointestinal adverse events and rash, with few reported grade 3 or higher treatment-related events, although toxicity may differ when combined with chemotherapy.

Outcomes: The co-primary outcomes are investigator-assessed progression-free survival by RECIST v1.1 and overall survival. Secondary outcomes include centrally reviewed progression-free survival, objective response rate, duration of response, adverse events graded by CTCAE v5, clinically significant changes in vital signs and laboratory values, pancreatic pain measured with EORTC QLQ-PAN26, global health status measured with EORTC QLQ-C30, and zoldonrasib pharmacokinetics through Cycle 5 Day 1.

Burden on patient: Estimated burden is moderate to high, driven primarily by intensive intravenous combination chemotherapy and associated clinic visits rather than unusual research procedures. Patients will require repeated infusions, laboratory monitoring, toxicity assessments, imaging for RECIST response, and long-term survival follow-up; those receiving modified FOLFIRINOX may also require prolonged fluorouracil infusion and pump management. Daily oral study drug or placebo adds adherence requirements, and the experimental arm includes pre-dose and post-dose pharmacokinetic blood sampling at selected visits through the start of Cycle 5. Quality-of-life questionnaires add limited burden, and no protocol-mandated research biopsy is specified.

Last updated: Jul 2026

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