Zoldonrasib plus Daraxonrasib vs Gemcitabine and Nab-Paclitaxel as first-line treatment for metastatic KRAS G12D pancreatic cancer

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This global phase 3 trial randomizes patients with untreated metastatic pancreatic ductal adenocarcinoma and KRAS G12D mutations to receive either daraxonrasib plus zoldonrasib or the standard regimen of gemcitabine and nab-paclitaxel as first-line therapy. The study is open-label and compares progression-free survival and overall survival between arms. Eligible participants have good performance status, measurable disease, and confirmed KRAS G12D status, and must have no prior systemic therapy for metastatic disease. Primary concerns include safety and tolerability of the combination versus chemotherapy, with predefined efficacy endpoints and interim analyses planned. Locations include multiple sites in the United States operated by major cancer centers.

Why it matters

Who can join: the full rules

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, including adenosquamous carcinoma, not previously treated in the locally advanced unresectable or metastatic setting.
* No prior treatment in the locally advanced unresectable or metastatic setting
* Diagnosis of metastatic disease ≤ 6 weeks prior to informed consent.
* Documented KRAS G12D mutation status.
* Measurable disease per RECIST v1.1.
* Adequate organ function (bone marrow, liver, kidney, coagulation).

Exclusion Criteria:

* Mutation status with known driver mutations for which there are approved targeted therapies.
* Acinar cell carcinoma, pancreatic neuroendocrine tumors, tumors involving islet cells or islet cell neoplasms, and other non-adenocarcinoma pancreatic malignancies.
* Tumors determined to originate from non-pancreatic primary sites.
* Prior treatment with MAPK-pathway targeted therapy or administration of RAS-targeted vaccine in the metastatic setting.
* Active or known history of untreated central nervous system metastatic or leptomeningeal 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.
* Additional inclusion \& exclusion criteria may apply.

Where it's running

• Mayo Clinic Arizona
  Phoenix, Arizona, United States Recruiting
• HonorHealth Research Institute
  Scottsdale, Arizona, United States Recruiting
• Mayo Clinic Florida
  Jacksonville, Florida, United States Recruiting
• Moffitt Cancer Center
  Tampa, Florida, United States Recruiting
• Mayo Clinic Rochester
  Rochester, Minnesota, United States Recruiting
• Rhode Island Hospital
  Providence, Rhode Island, United States Recruiting

Study contacts

• Study coordinator: Revolution Medicines Study Director
• Email: medinfo@revmed.com
• Phone: 1-844-2-REVMED

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• Zoldonrasib + chemotherapy vs placebo + chemotherapy as first-line treatment for metastatic KRAS G12D pancreatic cancer

  This trial tests whether adding zoldonrasib to standard chemotherapy helps people with newly diagnosed metastatic KRAS G12D pancreatic cancer.

  Recruiting at 25 sites Phase 3 Revolution Medicines, Inc. · Phoenix, Arizona and 24 other locations · NCT07621718

• Daraxonrasib alone or with gemcitabine and nab-paclitaxel for first-line metastatic pancreatic cancer

  This trial will see if daraxonrasib, alone or with gemcitabine and nab-paclitaxel, helps people with newly diagnosed metastatic pancreatic cancer live longer or slow tumor growth compared with standard gemcitabine and nab-paclitaxel.

  Recruiting at 61 sites Phase 3 Revolution Medicines, Inc. · Phoenix, Arizona and 81 other locations · NCT07491445

• Atebimetinib plus gemcitabine and nab‑paclitaxel as first‑line treatment for metastatic pancreatic cancer

  This trial will test whether adding the MAPK pathway drug atebimetinib to gemcitabine and nab‑paclitaxel helps people with newly diagnosed metastatic pancreatic ductal adenocarcinoma live longer.

  Recruiting at 76 sites Phase 3 Immuneering Corporation · Huntsville, Alabama and 75 other locations · NCT07562152

• RMC-5127 for advanced cancers with KRAS G12V mutation

  This trial will test whether the experimental drug RMC-5127, alone or with daraxonrasib or cetuximab, helps adults with advanced KRAS G12V-mutant solid tumors.

  Recruiting at 9 sites Phase 1 Revolution Medicines, Inc. · New Haven, Connecticut and 8 other locations · NCT07349537

• Daraxonrasib after surgery for resected pancreatic ductal adenocarcinoma (PDAC)

  This trial tests whether taking daraxonrasib after surgery can help prevent cancer from coming back in adults with resected PDAC who completed perioperative chemotherapy.

  Recruiting at 85 sites Phase 3 Revolution Medicines, Inc. · Birmingham, Alabama and 85 other locations · NCT07252232

• TNG462 combined with RAS inhibitors or chemotherapy for MTAP‑loss pancreatic and RAS‑mutant lung cancer

  This trial will test whether taking oral TNG462 together with RAS inhibitors or standard chemotherapy is safe and helps people with MTAP‑loss pancreatic cancer or RAS‑mutant non‑small cell lung cancer.

  Recruiting at 18 sites Phase 1/2 Tango Therapeutics, Inc. · Scottsdale, Arizona and 17 other locations · NCT06922591

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.