Pancreatic CancerPhase 3RASolute 302NCT06625320
Phase 3 Study of Daraxonrasib (RMC-6236) in Patients With Previously Treated Metastatic Pancreatic Ductal Adenocarcinoma (PDAC)
A Phase 3 study testing RMC-6236, Gemcitabine and nab-paclitaxel in people with Pancreatic Cancer and PDAC, run by Revolution Medicines, Inc. at 60 sites in 7 countries.
Trial summary
The purpose of this study is to evaluate the safety and efficacy of a novel RAS(ON) inhibitor compared to standard(s) of care (SOC) treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreatic Cancer, PDAC, PDAC - Pancreatic Ductal Adenocarcinoma
- What is being tested?
- RMC-6236, 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
- 500 participants
- Where
- 60 sitesin 7 countries
- Study dates
- 16 Oct 2024to Dec 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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 PDAC with metastatic disease.
- Measurable disease per RECIST 1.1.
- Adequate organ function (bone marrow, liver, kidney, coagulation)
- Documented RAS mutation status, either mutant or wild-type. RAS mutations defined as nonsynonymous mutations in KRAS, NRAS, or HRAS at codons 12, 13, or 61 (G12, G13, or Q61).
- Able to take oral medications.
Who cannot join
- Prior therapy with direct RAS-targeted therapy (eg. degraders and/or inhibitors).
- History of or known central nervous system metastatic disease.
- Any conditions that may affect the ability to take or absorb study treatment
- Major surgery within 4 weeks prior to randomization.
- Patient is unable or unwilling to comply with protocol-required study visits or procedures
Trial locations and contacts
60 sites in 7 countries.
60 sites in 7 countries
United States37 sites
University of Michigan
Ann Arbor, Michigan, 48109
Rocky Mountain Cancer
Aurora, Colorado, 80012
Johns Hopkins
Baltimore, Maryland, 21287
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Roswell Park Cancer Institute
Buffalo, New York, 14263
The University of Chicago Medical Center
Chicago, Illinois, 60637
University of Cincinnati Medical Center
Cincinnati, Ohio, 45219
Texas Oncology Sammons
Dallas, Texas, 75246
Karmanos Cancer Institute
Detroit, Michigan, 48201
City of Hope-Duarte
Duarte, California, 91010
Duke University Medical Center
Durham, North Carolina, 27710
Virginia Cancer Specialists
Fairfax, Virginia, 22031
Banner MD Anderson Cancer Center
Gilbert, Arizona, 85234
The Queen's Medical Center
Honolulu, Hawaii, 96813
MD Anderson Cancer Center
Houston, Texas, 77030
Texas Oncology - Central South
Irving, Texas, 75063
Mayo Clinic Cancer Center - Florida
Jacksonville, Florida, 32224
Cedars-Sinai Medical Center
Los Angeles, California, 90048
UCLA
Los Angeles, California, 90095
University of Miami Sylvester Comprehensive Cancer Center
Miami, Florida, 33136
Sarah Cannon Research Institute (Tennessee)
Nashville, Tennessee, 37203
NYU Lagone Health
New York, New York, 10016
Memorial Sloan Kettering Cancer Center
New York, New York, 10022
Columbia University Medical Center
New York, New York, 10032
Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104
Cancer Care Centers of Brevard Inc
Palm Bay, Florida, 32909
Abramson Cancer Center Clinical Research Unit
Philadelphia, Pennsylvania, 19104
Mayo Clinic Cancer Center - Phoenix
Phoenix, Arizona, 85054
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
Oregon Health and Science University
Portland, Oregon, 97239
Mayo Clinic Cancer Center - Rochester
Rochester, Minnesota, 55905
Huntsman Cancer Institute
Salt Lake City, Utah, 84112
UC San Diego Health Moores Cancer Center
San Diego, California, 92037
Mission Hall UCSF
San Francisco, California, 94158
Fred Hutchinson Cancer Center
Seattle, Washington, 98109
Washington University
St Louis, Missouri, 63110
Moffitt Cancer Center
Tampa, Florida, 33612
Japan6 sites
National Cancer Center
Chiba, 277-8577
Aichi Cancer Center
Nagoya, 4648681
Osaka International Cancer
Osaka, 541-8567
National Cancer Center Hospital
Tokyo, 104-0045
Cancer Institute Hospital of JFCR
Tokyo, 135-8550
Kanagawa Cancer Center
Yokohama, 241-8515
France4 sites
Institut Paoli Calmettes
Marseille, 13009
Centre Eugene Marquis
Rennes, 35042
Hopital Paul Brousse
Villejuif, 94804
Gustave Roussy
Villejuif, 94805
Germany4 sites
Charité Universitätsmedizin, Campus Berlin Mitte
Berlin, 13353
Nationales Centrum fur
Heidelberg, 69120
Universitatsklinikum Ulm, Zentru
München, 81377
Universitatsklinikum Ulm
Ulm, 89081
Italy4 sites
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan
IEO-Istituto Europeo di Oncologia
Milan
IOV-Istituto Oncologico
Padova, 35128
Azienda Ospedaliera
Pisa, 56126
Spain4 sites
Hospital Unversitari
Barcelona, 08035
Hospital 12 de Octubre
Madrid, 28041
Clinica Universidad de Navarra
Pamplona, 31008
Hospital Clinico de Valencia
Valencia, 46010
About this study
Official title: RASolute 302: A Phase 3 Multicenter, Open-label, Randomized Study of Daraxonrasib (RMC-6236) Versus Investigator's Choice of Standard of Care Therapy in Patients With Previously Treated Metastatic Pancreatic Ductal Adenocarcinoma (PDAC)
The purpose of this study is to evaluate the safety and efficacy of a novel RAS(ON) inhibitor compared to standard(s) of care (SOC) treatment.
Read the detailed description
This is a global, randomized, open-label, Phase 3 study designed to evaluate whether treatment with RMC-6236 will improve progression free survival (PFS) or overall survival (OS) compared to Investigator's choice of standard of care chemotherapy in patients with metastatic PDAC who were previously treated with one prior line of therapy with 5-fluorouracil (5-FU) based or gemcitabine-based regimen.
Patients will be randomized in a 1:1 ratio to receive RMC-6236 (Arm A) or Investigator's choice of standard of care chemotherapy (Arm B).
- Being tested
- RMC-6236, Gemcitabine, nab-paclitaxel, Irinotecan, Liposomal irinotecan
- Keywords
- Pancreatic Cancer, PDAC, Pancreatic Ductal Adenocarcinoma, RAS, KRAS, NRAS, HRAS, RAS Wild-Type, RAS Q61 Mutation, RAS G12 Mutation, RAS G13 Mutation
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RMC-6236Drug
Oral Tablets
GemcitabineDrug
intravenous (IV) infusion
nab-paclitaxelDrug
IV infusion
IrinotecanDrug
IV infusion
Liposomal irinotecanDrug
IV infusion
5-fluorouracilDrug
IV infusion
leucovorinDrug
IV infusion
OxaliplatinDrug
IV infusion
| Study group | Role | What they receive |
|---|---|---|
| RMC-6236 | Experimental | Study drug Receives: Drug: RMC-6236 |
| Investigator's choice of standard of care therapy | Active comparator | Patients randomized to Investigator's choice of standard of care chemotherapy will receive one of the following four treatments:
* Gemcitabine and nab-paclitaxel (GnP)
* Oxaliplatin, leucovorin, irinotecan, and 5-FU (Modified FOLFIRINOX: mFOLFIRINOX)
* Liposomal irinotecan (Nal-IRI + 5-FU/LV)
* Oxaliplatin, leucovorin and 5-FU IV (FOLFOX) Receives: Drug: Gemcitabine; Drug: nab-paclitaxel; Drug: Irinotecan; Drug: Liposomal irinotecan; Drug: 5-fluorouracil; Drug: leucovorin; Drug: Oxaliplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival (PFS) in the RAS G12-mutant population
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 blinded independent central review (BICR)
Measured: Up to approximately 3 years
Overall survival (OS) in the RAS G12-mutant population
OS is defined as the time from randomization until death from any cause.
Measured: Up to approximately 3 years
Secondary outcomes (10)
PFS in the all-patient population
PFS is defined as the time from randomization until disease progression or death from any cause, whichever occurs first. Progression is per RECIST v1.1 and as assessed by BICR.
Measured: Up to approximately 3 years
OS in the all-patient population
OS is defined as the time from randomization until death from any cause.
Measured: Up to approximately 3 years
Objective response in the RAS G12 and all-patient populations
Objective response is defined as partial response (PR) or completed response (CR) per RECIST v1.1, assessed by BICR.
Measured: Up to approximately 3 years
Time to deterioration (TTD) in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Pancreatic Cancer Module (EORTC QLQ-PAN26) in the RAS G12 and all-patient populations
TTD is defined as the time from randomization to the first occurrence of deterioration as defined by a change of at least 10 points, or death, whichever occurs first, in each subscale in EORTC QLQ-PAN26.
Measured: Up to approximately 3 years
Time to deterioration (TTD) in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in the RAS G12 and all-patient populations
TTD is defined as the time from randomization to the first occurrence of deterioration as defined by a change of at least 10 points, or death, whichever occurs first, in each subscale and global QoL score in EORTC QLQ-C30.
Measured: Up to approximately 3 years
Objective response per investigator in RAS G12 and all- patient populations
Objective response is defined as PR or CR per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, as assessed by the investigator.
Measured: Up to approximately 3 years
Duration of response (DOR) in RAS G12 and all-patient populations
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 BICR and by the investigator.
Measured: Up to approximately 3 years
Time to response (TTR) in RAS G12 and all-patient populations
TTR is defined as time from randomization to first evidence of objective response (PR or CR), as assessed by BICR and by the investigator.
Measured: Up to approximately 3 years
Percentage of patients with adverse events (AEs)
Measured: Up to approximately 3 years
Pharmacokinetics of RMC-6236 in RAS G12 and all-patient populations
Pharmacokinetics are defined by blood concentrations of RMC-6236 over time.
Measured: Up to approximately 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2024
- Study start16 Oct 2024
- Primary completionJun 2026 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- 500 participants (actual)
Sponsor and investigators
- Lead sponsor
- Revolution Medicines, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Revolution Medicines
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06625320
- Sponsor's protocol ID
- RMC-6236-302
- Acronym
- RASolute 302
- Status last verified
- Nov 2025
- First submitted
- 20 Sep 2024
- Last updated
- 2 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Expanded access
- Available
Publications
O'Reilly EM, Wainberg ZA, Hendifar AE, Borad MJ, Pietrantonio F, Pant S, Hammel P, Cremolini C, Manji GA, Oberstein PE, Garrido-Laguna I, Springfeld C, Azad NS, Ueno M, Chui SY, Zhang Y, Patel H, Lee Y, Salman Z, Wolpin BM; RASolute 302 Trial Investigators. Daraxonrasib or Chemotherapy in Previously Treated Metastatic Pancreatic Cancer. N Engl J Med. 2026 Jul 23;395(4):325-337. doi: 10.1056/NEJMoa2605555. Epub 2026 May 31.
PubMed 42223072
Study at a glance
From the registry record, last updated by the sponsor on 2 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- RASolute 302: A Phase 3 Multicenter, Open-label, Randomized Study of Daraxonrasib (RMC-6236) Versus Investigator's Choice of Standard of Care Therapy in Patients With Previously Treated Metastatic Pancreatic Ductal Adenocarcinoma (PDAC)
- ClinicalTrials.gov ID
- NCT06625320
- Acronym / sponsor ID
- RASolute 302 / RMC-6236-302
- Keywords
- Pancreatic Cancer, PDAC, Pancreatic Ductal Adenocarcinoma, RAS, KRAS, NRAS, HRAS, RAS Wild-Type
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 500 participants (actual)
- Lead sponsor
- Revolution Medicines, Inc.Industry (pharma, biotech, devices)
- Study start
- 16 Oct 2024 (actual)
- Primary completion
- Jun 2026 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 3 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the safety and efficacy of a novel RAS(ON) inhibitor compared to standard(s) of care (SOC) treatment.
Detailed description
This is a global, randomized, open-label, Phase 3 study designed to evaluate whether treatment with RMC-6236 will improve progression free survival (PFS) or overall survival (OS) compared to Investigator's choice of standard of care chemotherapy in patients with metastatic PDAC who were previously treated with one prior line of therapy with 5-fluorouracil (5-FU) based or gemcitabine-based regimen.
Patients will be randomized in a 1:1 ratio to receive RMC-6236 (Arm A) or Investigator's choice of standard of care chemotherapy (Arm B).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| RMC-6236 | Experimental | Drug: RMC-6236Study drug |
| Investigator's choice of standard of care therapy | Active comparator | Drug: Gemcitabine, Drug: nab-paclitaxel, Drug: Irinotecan, Drug: Liposomal irinotecan, Drug: 5-fluorouracil, Drug: leucovorin, Drug: OxaliplatinPatients randomized to Investigator's choice of standard of care chemotherapy will receive one of the following four treatments: * Gemcitabine and nab-paclitaxel (GnP) * Oxaliplatin, leucovorin, irinotecan, and 5-FU (Modified FOLFIRINOX: mFOLFIRINOX) * Liposomal irinotecan (Nal-IRI + 5-FU/LV) * Oxaliplatin, leucovorin and 5-FU IV (FOLFOX) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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 PDAC with metastatic disease.
- Measurable disease per RECIST 1.1.
- Adequate organ function (bone marrow, liver, kidney, coagulation)
Key exclusion criteria (5 listed)
- Prior therapy with direct RAS-targeted therapy (eg. degraders and/or inhibitors).
- History of or known central nervous system metastatic disease.
- Any conditions that may affect the ability to take or absorb study treatment
- Major surgery within 4 weeks prior to randomization.
- Patient is unable or unwilling to comply with protocol-required study visits or procedures
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RMC-6236Oral Tablets | Drug | RMC-6236 |
| Gemcitabineintravenous (IV) infusion | Drug | Investigator's choice of standard of care therapy |
| nab-paclitaxelIV infusion | Drug | Investigator's choice of standard of care therapy |
| IrinotecanIV infusion | Drug | Investigator's choice of standard of care therapy |
| Liposomal irinotecanIV infusion | Drug | Investigator's choice of standard of care therapy |
| 5-fluorouracilIV infusion | Drug | Investigator's choice of standard of care therapy |
| leucovorinIV infusion | Drug | Investigator's choice of standard of care therapy |
| OxaliplatinIV infusion | Drug | Investigator's choice of standard of care therapy |
Primary outcome
Progression free survival (PFS) in the RAS G12-mutant population
Time frame: Up to approximately 3 years
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 blinded independent central review (BICR)
Overall survival (OS) in the RAS G12-mutant population
Time frame: Up to approximately 3 years
OS is defined as the time from randomization until death from any cause.
10 secondary outcomes
PFS in the all-patient population
Time frame: Up to approximately 3 years
OS in the all-patient population
Time frame: Up to approximately 3 years
Objective response in the RAS G12 and all-patient populations
Time frame: Up to approximately 3 years
Time to deterioration (TTD) in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Pancreatic Cancer Module (EORTC QLQ-PAN26) in the RAS G12 and all-patient populations
Time frame: Up to approximately 3 years
Time to deterioration (TTD) in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in the RAS G12 and all-patient populations
Time frame: Up to approximately 3 years
Objective response per investigator in RAS G12 and all- patient populations
Time frame: Up to approximately 3 years
Duration of response (DOR) in RAS G12 and all-patient populations
Time frame: Up to approximately 3 years
Time to response (TTR) in RAS G12 and all-patient populations
Time frame: Up to approximately 3 years
Percentage of patients with adverse events (AEs)
Time frame: Up to approximately 3 years
Pharmacokinetics of RMC-6236 in RAS G12 and all-patient populations
Time frame: Up to approximately 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jun 2026.
- Derived from this study: PubMed 42223072O'Reilly EM, Wainberg ZA, Hendifar AE, Borad MJ, Pietrantonio F, Pant S, Hammel P, Cremolini C, Manji GA, Oberstein PE, Garrido-Laguna I, Springfeld C, Azad NS, Ueno M, Chui SY, Zhang Y, Patel H, Lee Y, Salman Z, Wolpin BM; RASolute 302 Trial Investigators. Daraxonrasib or Chemotherapy in Previously Treated Metastatic Pancreatic Cancer. N Engl J Med. 2026 Jul 23;395(4):325-337. doi: 10.1056/NEJMoa2605555. Epub 2026 May 31.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Revolution Medicines
60 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing RMC-6236, Gemcitabine and nab-paclitaxel in people with Pancreatic Cancer and PDAC, run by Revolution Medicines, Inc. at 60 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 2 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 60 sites in United States, Japan, France, Germany, Italy and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression free survival (PFS) in the RAS G12-mutant population (time frame: Up to approximately 3 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06625320, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jun 2026.