Pancreatic CancerPhase 3RASolute 309NCT07805954
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
A Phase 3 study testing daraxonrasib, gemcitabine and nab-paclitaxel in people with Pancreatic Cancer and Pancreatic Cancer Metastatic, run by Revolution Medicines, Inc. at 5 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreatic Cancer, Pancreatic Cancer Metastatic, PDAC
- What is being tested?
- daraxonrasib, gemcitabine and nab-paclitaxel
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 400 participants
- Where
- 5 sitesUnited States
- Study dates
- 28 Aug 2026to Apr 2030
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
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- 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.
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
United States5 sites, 5 recruiting
- Recruiting
Mayo Clinic Florida
Jacksonville, Florida, 32224
Hani M. Babiker, 855-776-0015
- Recruiting
Mayo Clinic Arizona
Phoenix, Arizona, 85054
Tanios S. Bekaii-Saab, 855-776-0015
- Recruiting
Mayo Clinic Rochester
Rochester, Minnesota, 55905
Ben George, 855-776-0015
- Recruiting
HonorHealth Research Institute
Scottsdale, Arizona, 85258
Amy Malensek, 480-323-1350, amalensek@honorhealth.com
- Recruiting
Moffitt Cancer Center
Tampa, Florida, 33612
Cheyenne Schneider, 813-745-5166, Cheyenne.Schneider@moffitt.org
About this study
Official title: 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
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.
Read the detailed description
This is a global, randomized, open-label, Phase 3 study designed to evaluate whether treatment with daraxonrasib plus zoldonrasib will improve progression-free survival and/or overall survival compared with standard gemcitabine and nab-paclitaxel when given as first-line treatment in patients with metastatic KRAS G12D-mutated pancreatic adenocarcinoma.
Patients will be randomized to one of two arms: daraxonrasib + zoldonrasib (Arm A) or gemcitabine and nab-paclitaxel (Arm B).
- Conditions
- Pancreatic Cancer, Pancreatic Cancer Metastatic, PDAC, PDAC - Pancreatic Ductal Adenocarcinoma, Pancreatic Ductal Adenocarcinoma (PDAC), Pancreatic Adenocarcinoma Metastatic
- Being tested
- daraxonrasib, gemcitabine, nab-paclitaxel, zoldonrasib
- Keywords
- Pancreatic Cancer, PDAC, Pancreatic Ductal Adenocarcinoma, RAS, KRAS, RAS Mutation, Pancreatic Cancer Metastatic, Pancreatic Adenocarcinoma Metastatic, Pancreatic Adenosquamous Carcinoma, Pancreatic Adenocarcinoma
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
daraxonrasibDrug
oral tablets
gemcitabineDrug
intravenous (IV) infusion
nab-paclitaxelDrug
IV infusion
zoldonrasibDrug
oral tablets
| Study group | Role | What they receive |
|---|---|---|
| Arm A: daraxonrasib + zoldonrasib | Experimental | combination of study drugs Receives: Drug: daraxonrasib; Drug: zoldonrasib |
| Arm B: gemcitabine and nab-paclitaxel | Experimental | chemotherapy Receives: Drug: gemcitabine; Drug: nab-paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival (PFS)
PFS is defined as the time from randomization until disease progression or death from any cause, whichever occurs first. Progression is per response evaluation criteria in solid tumors (RECIST) v1.1 and as assessed by Investigator.
Measured: Up to approximately 4 years
Overall survival (OS)
OS is defined as the time from randomization until death from any cause.
Measured: Up to approximately 4 years
Secondary outcomes (9)
PFS by blinded independent central review (BICR)
PFS is 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
Measured: Up to approximately 4 years
Objective response rate (ORR)
Objective response is defined as partial response (PR) or complete response (CR) per RECIST v1.1, as assessed by the Investigator.
Measured: Up to approximately 4 years
Duration of response (DOR)
DOR is defined as time from first evidence of objective response (PR or CR) to disease progression or death due to any cause, whichever occurs first, as assessed by the investigator.
Measured: Up to approximately 4 years
Incidence of adverse events (AEs)
Percentage of patients with AEs as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5
Measured: Up to approximately 4 years
Changes in vital signs
Number of patients with changes from baseline in vital signs
Measured: Up to approximately 4 years
Changes in clinical laboratory test values
Number of patients with changes from baseline in clinical laboratory test values
Measured: Up to approximately 4 years
Concentration of daraxonrasib and zoldonrasib in Arm A
Pre-dose trough and post-dose blood concentrations of daraxonrasib and zoldonrasib at selected visits.
Measured: Up to Cycle 5 Day 1 (each cycle is 28 days)
Health-related outcome assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Pancreatic Cancer Module (EORTC QLQ-PAN26) pain scale
EORTC QLQ-PAN26 consists of 26 questions relating to disease symptoms, treatment side effects and emotional issues specific to pancreatic cancer. The pancreatic pain subscale assesses abdominal pain, back pain, and pain while lying down. Change in score from baseline in the pain subscale will be assessed with higher scores on the pain subscale indicating more severe pain and worsening function.
Measured: Up to approximately 4 years
Quality of life as assessed with European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) global health status score
EORTC QLQ-C30 consists of 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, pain, nausea/vomiting, dyspnoea, appetite loss, insomnia, constipation/diarrhea, and financial difficulties), and an overall scale for global health status. It uses a mix of 4-point scales and 7-point scales. Change from baseline in EORTC QLQ-C30 global health status will be assessed. Higher scores on functional scales reflect better functioning, whereas higher scores on symptom scales reflect higher symptom burden.
Measured: Up to approximately 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2026
- Study start28 Aug 2026
- Primary completionMar 2029 (estimated)
- Study completionApr 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pancreatic CancerStudies of the same condition, open and under way.
- More trials run by Revolution Medicines, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Revolution Medicines, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07805954
- Sponsor's protocol ID
- RMC-9805-309
- Acronym
- RASolute 309
- Status last verified
- Aug 2026
- First submitted
- 1 Sep 2026
- Last updated
- 16 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No