NSCLCPhase 3RASolve 308NCT07777822
Study of Pembrolizumab + Pemetrexed + Platinum Chemotherapy With or Without Zoldonrasib as First Line Treatment in Metastatic Non-squamous RAS G12D-Mutated NSCLC
A Phase 3 study testing zoldonrasib, pembrolizumab and pemetrexed + cisplatin /carboplatin in people with NSCLC and Non-small Cell Lung Cancer, run by Revolution Medicines, Inc. at 4 sites in United States.
Trial summary
The purpose of this study is to evaluate the efficacy of an investigational RAS(ON) inhibitor administered in combination with pembrolizumab and platinum-based chemotherapy doublet compared to placebo in combination with pembrolizumab and platinum-based chemotherapy doublet. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- NSCLC, Non-small Cell Lung Cancer, Non-Small Cell Lung Cancer NSCLC
- What is being tested?
- zoldonrasib, pembrolizumab and pemetrexed + cisplatin /carboplatin
- 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
- 430 participants
- Where
- 4 sitesUnited States
- Study dates
- 14 Aug 2026to Feb 2031
- 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, previously untreated metastatic non-squamous NSCLC.
- Known PD-L1 status
- Documented RAS G12D mutation status.
- Measurable disease per RECIST v1.1.
- Adequate organ function (bone marrow, liver, kidney, coagulation, thyroid).
- Able to take oral medications.
Who cannot join
- Prior treatment with systemic anticancer therapy in metastatic setting for NSCLC.
- Prior systemic therapy with any RAS-directed therapy.
- Untreated (symptomatic or asymptomatic) central nervous system metastatic disease.
- Any conditions that may affect the ability to take or absorb study drug.
- Major surgery on or within 28 days prior to randomization.
- Patient is unable or unwilling to comply with protocol-required study visits or procedures.
- Additional inclusion and exclusion criteria may apply
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States4 sites, 4 recruiting
- Recruiting
Alaska Oncology and Hematology
Anchorage, Alaska, 99508
Talia Wyckoff, 907-257-9851, talia@alaskaoncology.com
- Recruiting
Helios CR, Inc. - The Oncology Institute of Hope and Innovation - Fort Lauderdale
Fort Lauderdale, Florida, 33316
Kylee Charlemagne, 754-294-4466, kylee.charlemagne@heliosclinical.com
- Recruiting
Florida Clinical Trials Group, LLC
Plantation, Florida, 33322
Sandra Perez, 772-297-3057 ext. Ext 102, perezs@floridactg.com
- Recruiting
Florida Clinical Trials Group
Plantation, Florida, 33322
Sandra Perez, 772-297-3057 ext. Ext 102, perezs@floridactg.com
About this study
Official title: A Randomized, Double-blind, Phase 3 Study of Pembrolizumab + Pemetrexed + Platinum Chemotherapy With or Without Zoldonrasib (RMC-9805) as First Line Treatment in Patients With Metastatic Non-squamous RAS G12D-Mutated Non-small Cell Lung Cancer (RASolve 308)
The purpose of this study is to evaluate the efficacy of an investigational RAS(ON) inhibitor administered in combination with pembrolizumab and platinum-based chemotherapy doublet compared to placebo in combination with pembrolizumab and platinum-based chemotherapy doublet.
Read the detailed description
This is a Phase 3, global, randomized, double-blind study designed to evaluate whether treatment with zoldonrasib in combination with pembrolizumab and platinum-based chemotherapy doublet will improve progression-free survival compared to placebo in combination with pembrolizumab and platinum-based chemotherapy doublet when given to patients with previously untreated, 1L metastatic RAS G12D-mutated, non-squamous non-small cell lung cancer (NSCLC).
Patients will be randomized to one of two arms: zoldonrasib + pembrolizumab + platinum-based chemotherapy doublet (Arm A) or placebo + pembrolizumab + platinum-based chemotherapy doublet (Arm B).
- Conditions
- NSCLC, Non-small Cell Lung Cancer, Non-Small Cell Lung Cancer NSCLC, Non-Squamous Non Small Cell Lung Cancer, Lung Cancer (NSCLC), Metastatic NSCLC - Non-Small Cell Lung Cancer
- Being tested
- zoldonrasib, Placebo, pembrolizumab, pemetrexed + cisplatin /carboplatin
- Keywords
- NSCLC, Non-Small Cell Lung Cancer, Non-Squamous Non Small Cell Lung Cancer, Metastatic Non-Squamous Non-Small Cell Lung Cancer, RAS, KRAS, NRAS, HRAS, RAS Mutation, Lung Cancer, G12D, RAS G12D
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Lung 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
pembrolizumabDrug
IV infusion or Subcutaneous injection
pemetrexed + cisplatin /carboplatinDrug
Also called Platinum-based chemotherapy doublet
IV infusion of either pemetrexed + cisplatin or pemetrexed + carboplatin
| Study group | Role | What they receive |
|---|---|---|
| Arm A: zoldonrasib + pembrolizumab + chemotherapy doublet | Experimental | study drug in combination with pembrolizumab and platinum-based chemotherapy doublet Receives: Drug: zoldonrasib; Drug: pembrolizumab; Drug: pemetrexed + cisplatin /carboplatin |
| Arm B: placebo + pembrolizumab + chemotherapy doublet | Placebo comparator | placebo in combination with pembrolizumab and platinum-based chemotherapy doublet Receives: Drug: Placebo; Drug: pembrolizumab; Drug: pemetrexed + cisplatin /carboplatin |
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 blinded independent central review (BICR).
Measured: Up to approximately 5 years
Secondary outcomes (11)
Overall survival (OS)
OS is defined as the time from randomization until death from any cause.
Measured: Up to approximately 5 years
Objective response rate (ORR)
Objective response is defined as partial response (PR) or complete response (CR) as assessed per RECIST v1.1 by BICR.
Measured: Up to approximately 5 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. Response and progression are per RECIST v1.1, as assessed by BICR.
Measured: Up to approximately 5 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 5 years
Changes in vital signs
Number of patients with changes in vital signs.
Measured: Up to approximately 5 years
Changes in clinical laboratory test values
Number of patients with changes in clinical laboratory test values.
Measured: Up to approximately 5 years
Quality of life as assessed with European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
EORTC QLQ-C30 is a 30-item cancer-specific instrument consisting of 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, nausea and vomiting, and pain), 7 single item scales (pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties), and a 2-item global health status/quality of life scale. Change from baseline in EORTC QLQ-C30 physical functioning scale and 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 5 years
Time to confirmed deterioration in physical function and global health status, as measured by EORTC QLQ-C30
Time to confirmed deterioration in physical functioning subscale and overall global health status scale, as measured by EORTC QLQ-C30. Higher scores on the Higher scores on the EORTC QLQ-C30 functional scales reflect better functioning, whereas higher scores on symptom the scales reflect higher symptom burden. Time to confirmed deterioration in EORTC QLQ-C30 physical functioning subscale and overall health status scale is defined as the time from randomization until the date of the first clinically meaningful deterioration, or death.
Measured: Up to approximately 5 years
Changes in Non-Small Cell Lung Cancer (NSCLC)-related symptoms, measured by the NSCLC-Symptom Assessment Questionnaire (NSCLC-SAQ)
The NSCLC-SAQ is a participant reported outcome measure with seven items assessing key NSCLC symptoms such as: cough, pain, dyspnea, fatigue, and appetite. Change from baseline in pulmonary symptoms of cough and dyspnea will be evaluated, with higher scores indicating more severe symptoms.
Measured: Up to approximately 5 years
Time to Confirmed Deterioration of NSCLC-related symptoms, as measured by NSCLC-SAQ
Time to confirmed deterioration in patient-reported pulmonary symptoms of cough and dypsnea, as measured by NSCLC-SAQ. Higher scores for the pulmonary symptoms on the NSCLC-SAQ indicate more severe symptoms. Time to confirmed deterioration in NSCLC-SAQ measures is defined as the time from randomization until the date of the first clinically meaningful deterioration, or death.
Measured: Up to approximately 5 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 21 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2026
- Study start14 Aug 2026
- Primary completionOct 2029 (estimated)
- Study completionFeb 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NSCLCStudies 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
- 430 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
- NCT07777822
- Sponsor's protocol ID
- RMC-9805-308
- Acronym
- RASolve 308
- Status last verified
- Aug 2026
- First submitted
- 17 Aug 2026
- Last updated
- 4 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Phase 3 Study of Pembrolizumab + Pemetrexed + Platinum Chemotherapy With or Without Zoldonrasib (RMC-9805) as First Line Treatment in Patients With Metastatic Non-squamous RAS G12D-Mutated Non-small Cell Lung Cancer (RASolve 308)
- ClinicalTrials.gov ID
- NCT07777822
- Acronym / sponsor ID
- RASolve 308 / RMC-9805-308
- Conditions
- NSCLC, Non-small Cell Lung Cancer, Non-Small Cell Lung Cancer NSCLC, Non-Squamous Non Small Cell Lung Cancer, Lung Cancer (NSCLC), Metastatic NSCLC - Non-Small Cell Lung Cancer
- Keywords
- NSCLC, Non-Small Cell Lung Cancer, Non-Squamous Non Small Cell Lung Cancer, Metastatic Non-Squamous Non-Small Cell Lung Cancer, RAS, KRAS, NRAS, HRAS
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 430 participants (estimated)
- Lead sponsor
- Revolution Medicines, Inc.Industry (pharma, biotech, devices)
- Study start
- 14 Aug 2026 (actual)
- Primary completion
- Oct 2029 (estimated)
- Study completion
- Feb 2031 (estimated)
- First posted
- 20 Aug 2026 (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 efficacy of an investigational RAS(ON) inhibitor administered in combination with pembrolizumab and platinum-based chemotherapy doublet compared to placebo in combination with pembrolizumab and platinum-based chemotherapy doublet.
Detailed description
This is a Phase 3, global, randomized, double-blind study designed to evaluate whether treatment with zoldonrasib in combination with pembrolizumab and platinum-based chemotherapy doublet will improve progression-free survival compared to placebo in combination with pembrolizumab and platinum-based chemotherapy doublet when given to patients with previously untreated, 1L metastatic RAS G12D-mutated, non-squamous non-small cell lung cancer (NSCLC).
Patients will be randomized to one of two arms: zoldonrasib + pembrolizumab + platinum-based chemotherapy doublet (Arm A) or placebo + pembrolizumab + platinum-based chemotherapy doublet (Arm B).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A: zoldonrasib + pembrolizumab + chemotherapy doublet | Experimental | Drug: zoldonrasib, Drug: pembrolizumab, Drug: pemetrexed + cisplatin /carboplatinstudy drug in combination with pembrolizumab and platinum-based chemotherapy doublet |
| Arm B: placebo + pembrolizumab + chemotherapy doublet | Placebo comparator | Drug: Placebo, Drug: pembrolizumab, Drug: pemetrexed + cisplatin /carboplatinplacebo in combination with pembrolizumab and platinum-based chemotherapy doublet |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 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, previously untreated metastatic non-squamous NSCLC.
- Known PD-L1 status
- Documented RAS G12D mutation status.
Key exclusion criteria (7 listed)
- Prior treatment with systemic anticancer therapy in metastatic setting for NSCLC.
- Prior systemic therapy with any RAS-directed therapy.
- Untreated (symptomatic or asymptomatic) central nervous system metastatic disease.
- Any conditions that may affect the ability to take or absorb study drug.
- Major surgery on or within 28 days prior to randomization.
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 |
|---|---|---|
| zoldonrasiboral tablets | Drug | Arm A: zoldonrasib + pembrolizumab + chemotherapy doublet |
| Placebooral tablets | Drug | Arm B: placebo + pembrolizumab + chemotherapy doublet |
| pembrolizumabIV infusion or Subcutaneous injection | Drug | Arm A: zoldonrasib + pembrolizumab + chemotherapy doublet, Arm B: placebo + pembrolizumab + chemotherapy doublet |
| pemetrexed + cisplatin /carboplatinAlso: Platinum-based chemotherapy doubletIV infusion of either pemetrexed + cisplatin or pemetrexed + carboplatin | Drug | Arm A: zoldonrasib + pembrolizumab + chemotherapy doublet, Arm B: placebo + pembrolizumab + chemotherapy doublet |
Primary outcome
Progression free survival (PFS)
Time frame: Up to approximately 5 years
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 blinded independent central review (BICR).
11 secondary outcomes
Overall survival (OS)
Time frame: Up to approximately 5 years
Objective response rate (ORR)
Time frame: Up to approximately 5 years
Duration of response (DOR)
Time frame: Up to approximately 5 years
Incidence of adverse events (AEs)
Time frame: Up to approximately 5 years
Changes in vital signs
Time frame: Up to approximately 5 years
Changes in clinical laboratory test values
Time frame: Up to approximately 5 years
Quality of life as assessed with European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
Time frame: Up to approximately 5 years
Time to confirmed deterioration in physical function and global health status, as measured by EORTC QLQ-C30
Time frame: Up to approximately 5 years
Changes in Non-Small Cell Lung Cancer (NSCLC)-related symptoms, measured by the NSCLC-Symptom Assessment Questionnaire (NSCLC-SAQ)
Time frame: Up to approximately 5 years
Time to Confirmed Deterioration of NSCLC-related symptoms, as measured by NSCLC-SAQ
Time frame: Up to approximately 5 years
Concentration of zoldonrasib in Arm A
Time frame: Up to Cycle 5 Day 1 (each cycle is 21 days)
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 4 Nov 2026.
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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.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing zoldonrasib, pembrolizumab and pemetrexed + cisplatin /carboplatin in people with NSCLC and Non-small Cell Lung Cancer, run by Revolution Medicines, Inc. at 4 sites in United States.
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 8 inclusion and 7 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: looking for participants now, as of the sponsor's last update on 4 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. 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. Some participants in this study may receive a placebo. 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?
Contact Revolution Medicines Study Director (1-844-2-REVMED, medinfo@revmed.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression free survival (PFS) (time frame: Up to approximately 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Nov 2026.