Pancreatic CancerPhase 3RASolute 305NCT07621718
Study of Zoldonrasib + Chemo of Investigator's Choice vs Placebo + Chemo of Investigator's Choice as First-line Treatment in Metastatic KRAS G12D-mutated Pancreatic Adenocarcinoma ( RASolute 305 )
A Phase 3 study testing Zoldonrasib, Oxaliplatin and Leucovorin (Calcium Folinate) in people with Pancreatic Cancer and Pancreatic Cancer Metastatic, run by Revolution Medicines, Inc. at 19 sites in 2 countries.
Trial summary
The purpose of this study is to evaluate the efficacy of an investigational RAS(ON) inhibitor administered in combination with chemotherapy compared to placebo in combination with 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?
- Zoldonrasib, Oxaliplatin and Leucovorin (Calcium Folinate)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 670 participants
- Where
- 19 sitesin 2 countries
- Study dates
- 22 May 2026to 22 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.
- Diagnosis of metastatic disease ≤ 6 weeks prior to screening.
- Documented KRAS G12D mutation status.
- Measurable disease per RECIST v1.1.
- Adequate organ function (bone marrow, liver, kidney, coagulation).
- Able to take oral medications.
Who cannot join
- Prior treatment with systemic anticancer therapy in unresectable locally advanced or metastatic setting.
- Prior systemic RAS-targeted therapy any time prior to randomization.
- Presence of other known driver mutations with approved targeted therapies
- Active or known history of untreated central nervous system metastatic 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.
Trial locations and contacts
19 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
19 sites in 2 countries
United States18 sites, 18 recruiting
- Recruiting
Piedmont Cancer Institute
Atlanta, Georgia, 30318
Adams, 678-298-3238, kadams@piedmontcancerinstitute.com
- Recruiting
Piedmont Healthcare
Atlanta, Georgia, 30318
Mieri, 404-425-1777, Takiyyah.Hamilton@piedmont.org
- Recruiting
Johns Hopkins University
Baltimore, Maryland, 21287
Apostol, 410-502-7484, giclinicaltrials@jhmi.edu
- Recruiting
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Lindquist, 857-215-2351, DanielleA_Lindquist@DFCI.HARVARD.EDU
- Recruiting
University of Chicago Medical Center
Chicago, Illinois, 60637
Desgardin, 773-834-7188, adesgard@bsd.uchicago.edu
- Recruiting
Duke Cancer Center
Durham, North Carolina, 27710
Currier, 919-668-1861, gi-oncology-cru@dm.duke.edu
- Recruiting
Astera Cancer Care
East Brunswick, New Jersey, 08816
Yao, 732-390-7750 ext. ext 1012, eileen.peng@asterahealthcare.org
- Recruiting
University of Florida
Gainesville, Florida, 32610
Allegra, 352-294-5691, allisonallegra3@ufl.edu
Barnes, 352-273-8020, j.barnes1@ufl.edu
- Recruiting
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Ross, 713-794-1623, GIClinicalTrials@mdanderson.org
- Recruiting
Mayo Clinic Florida
Jacksonville, Florida, 32224
Babiker, 855-776-0015
- Recruiting
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232
Cardin, 800-811-8480, cip@vumc.org
- Recruiting
Rutgers Cancer University
New Brunswick, New Jersey, 08901
DiOrio, 732-235-2135, kassie.diorio@rutgers.edu
- Recruiting
Yale University
New Haven, Connecticut, 06511
Boateng, 203-314-7948, Kwasi.boateng@yale.edu
- Recruiting
Columbia University Irving Medical Center
New York, New York, 10032
Manji, 212-342-5162, cancerclinicaltrials@cumc.columbia.edu
- Recruiting
Mayo Clinic Arizona
Phoenix, Arizona, 85054
Bekaii-Saab, 855-776-0015
- Recruiting
Mayo Clinic Rochester
Rochester, Minnesota, 55905
Jazieh, 855-776-0015
- Recruiting
Moffitt Cancer Center
Tampa, Florida, 33612
Kim, 813-745-3691, Cheyenne.Schneider@moffitt.org
- Recruiting
The University of Arizona Cancer Center-North Campus
Tucson, Arizona, 85719
Zimmerman, 520-626-8286, priscaz@arizona.edu
United Kingdom1 site, 1 recruiting
- Recruiting
Royal Marsden Hospital
London, SW3 6JJ
About this study
Official title: 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
The purpose of this study is to evaluate the efficacy of an investigational RAS(ON) inhibitor administered in combination with chemotherapy compared to placebo in combination with chemotherapy.
Read the detailed description
This is a Phase 3, global, randomized, double-blind study designed to evaluate whether treatment with zoldonrasib in combination with Investigator choice of chemotherapy will improve progression-free survival or overall survival compared to placebo in combination with Investigator choice of chemotherapy when given to patients with previously untreated, 1L metastatic KRAS G12D-mutated pancreatic adenocarcinoma. Choice of chemotherapy (mFFX or GnP) will be at the discretion of the Investigator.
Patients will be randomized to one of two arms: zoldonrasib + Investigator choice of chemotherapy (Arm A) or placebo + Investigator choice of chemotherapy (Arm B).
- Conditions
- Pancreatic Cancer, Pancreatic Cancer Metastatic, PDAC, PDAC - Pancreatic Ductal Adenocarcinoma, Pancreatic Ductal Adenocarcinoma (PDAC), Pancreatic Adenocarcinoma Metastatic
- Being tested
- Zoldonrasib, Placebo, Oxaliplatin, Leucovorin (Calcium Folinate), 5-Fluorouracil
- 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.
ZoldonrasibDrug
oral tablets
PlaceboDrug
oral tablets
OxaliplatinDrug
IV infusion
Leucovorin (Calcium Folinate)Drug
IV infusion
5-FluorouracilDrug
IV infusion
IrinotecanDrug
IV infusion
Gemcitabine (GEM)Drug
IV infusion
Nab-paclitaxelDrug
IV infusion
| Study group | Role | What they receive |
|---|---|---|
| Arm A: zoldonrasib + chemotherapy | Experimental | study drug in combination with Investigator choice chemotherapy (mFFX or GnP) Receives: Drug: Zoldonrasib; Drug: Oxaliplatin; Drug: Leucovorin (Calcium Folinate); Drug: 5-Fluorouracil; Drug: Irinotecan; Drug: Gemcitabine (GEM); Drug: Nab-paclitaxel |
| Arm B: placebo + chemotherapy | Placebo comparator | placebo in combination with Investigator choice chemotherapy (mFFX or GnP) Receives: Drug: Placebo; Drug: Oxaliplatin; Drug: Leucovorin (Calcium Folinate); Drug: 5-Fluorouracil; Drug: Irinotecan; Drug: Gemcitabine (GEM); 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 assessed per response evaluation criteria in solid tumors (RECIST) v1.1 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 per 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 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) as assessed per RECIST v1.1 by Investigator and BICR.
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 and BICR.
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 clinically significant changes 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
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
Concentration of zoldonrasib in Arm A
Pre-dose trough and post-dose blood concentrations of zoldonrasib at selected visits.
Measured: Up to Cycle 5 Day 1 (each cycle is 28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2026
- Study start22 May 2026
- Primary completion30 Dec 2028 (estimated)
- Study completion22 Apr 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 670 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
- NCT07621718
- Sponsor's protocol ID
- RMC-9805-305
- Acronym
- RASolute 305
- Status last verified
- Jul 2026
- First submitted
- 26 May 2026
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No