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Study of Zoldonrasib (RMC-9805) Plus Daraxonrasib (RMC-6236) Versus Gemcitabine and Nab-Paclitaxel as First-Line Treatment in Metastatic KRAS G12D-Mutated Pancreatic Adenocarcinoma

RecruitingPhase 3

A Phase 3, Randomized, Open-Label Study of Zoldonrasib (RMC-9805) Plus Daraxonrasib (RMC-6236) Versus Gemcitabine and Nab-Paclitaxel as First-Line Treatment in Patients With Metastatic KRAS G12D-Mutated Pancreatic Adenocarcinoma

Who can join

Ages 18 and older · All sexes

Full eligibility criteria
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.

About the study

The purpose of this study is to evaluate the efficacy of combination therapy with two investigational RAS(ON) inhibitors (daraxonrasib and zoldonrasib) compared to chemotherapy.

What is being tested

Sponsor: Revolution Medicines, Inc. · Participants: 400 · Started: Aug 28, 2026

Contact the study team

Official record on ClinicalTrials.gov — NCT07805954

Locations in the U.S.

FloridaMoffitt Cancer Center, Tampa

Conditions

From ClinicalTrials.gov, data retrieved Sep 30, 2026. Each study sets its own eligibility; the study team decides who can join.