Advanced Solid TumorsPhase 1/2NCT07397338
Study of RAS(ON) Inhibitors in Combination With Ivonescimab in Patients With Solid Tumors
A Phase 1/2 study testing Daraxonrasib, Elironrasib and Zoldonrasib in people with Advanced Solid Tumors and Metastatic Solid Tumors, run by Revolution Medicines, Inc. at 19 sites in United States.
Trial summary
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of RAS(ON) inhibitors in combination with ivonescimab in adults with advanced or metastatic solid tumors with a RAS mutation. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumors, Metastatic Solid Tumors, Non-small Cell Lung Cancer (NSCLC)
- What is being tested?
- Daraxonrasib, Elironrasib and Zoldonrasib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 370 participants
- Where
- 19 sitesUnited States
- Study dates
- 30 Jan 2026to May 2029
- Phase
- Phase 1/2
- 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 confirmed, locally advanced or metastatic solid tumor malignancy with documented RAS mutation in KRAS, HRAS, or NRAS.
- Received and progressed or been intolerant to prior standard therapy (Part 1 Dose Exploration).
- Non-squamous NSCLC without a treatable driver mutation in other oncogenes that has not received prior systemic treatment (Arms A \& B for Part 2 Dose Expansion).
- Solid tumor or CRC previously treated with no more than 2 prior lines of therapy for advanced disease and progressed or been intolerant to prior standard therapies (Arm C for Part 2 Dose Expansion).
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- Measurable disease per RECIST v1.1
- Adequate organ function (bone marrow, liver, kidney, coagulation, endocrine).
- Able to take oral medications.
Who cannot join
- Head and neck squamous cell carcinoma.
- Any conditions that may affect the ability to take or absorb study drug.
- Major surgery within 4 weeks prior to receiving study drug(s).
- Patient is unable or unwilling to comply with protocol-required study visits or procedures.
- Other inclusion/exclusion criteria may apply.
Trial locations and contacts
19 sites in 1 country. Contact the study team or a site near you to ask about taking part.
19 sites in 1 country
United States19 sites, 19 recruiting
- Recruiting
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
Afshin Dowlati, 216-844-3951, Afshin.Dowlati@uhhospitals.org
- Recruiting
The Jame Outpatient Care West Campus
Columbus, Ohio, 43221
Jon Freshette, 614-685-7433, john.frechette@osumc.edu
- Recruiting
NEXT Virginia
Fairfax, Virginia, 22031
Maybelle De La Rosa, 703-783-4518, mdelarosa@nextoncology.com
- Recruiting
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, 07601
Joshua Zenreich, 551-996-1777, oncologyresearchreferral@hmhn.org
- Recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
Ly Nguyen, 832-794-3672, LMNguyen1@mdanderson.org
- Recruiting
NEXT Dallas
Irving, Texas, 75039
Mofopefoluwa "Fope" Akinwale, 972-893-8800, fakinwale@nextoncology.com
- Recruiting
University of Kentucky HealthCare (UK HealthCare)
Lexington, Kentucky, 40536
Heather Pavlik, 859-323-2354, heather.schroer@uky.edu
- Recruiting
USC Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Lorraine Martinez Seng, RN, 323-865-0967, Lorraine.Martinez@med.usc.edu
- Recruiting
Tennessee Oncology
Nashville, Tennessee, 37023
Henry Black, 615-879-6410, hblack@tnonc.com
- Recruiting
Laura & Isaac Perlmutter Cancer Center at NYU Langone Health - NYU POC
New York, New York, 10016
cancertrials@nyulangone.org
- Recruiting
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
Erin Mulhall, 212-241-1013, erin.mulhall@mssm.edu
- Recruiting
Eastern Connecticut Hematology and Oncology Associates
Norwich, Connecticut, 06360
Spiro Curis, 860-886-8362 ext. ext 251, Scuris@echoct.com
- Recruiting
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
Ana Palmer, 878-261-6102, palmerah@upmc.edu
- Recruiting
OHSU Knight Cancer Institute
Portland, Oregon, 97239
Cassie Tompkins, 503-418-3451, tompkica@ohsu.edu
- Recruiting
Health Partners Cancer Center at Regions Hospital
Saint Paul, Minnesota, 55101
Lisa Wahowske, 651-254-1517, Lisa.A.Wahowske@HealthPartners.com
- Recruiting
NEXT Oncology
San Antonio, Texas, 78229
Jordan Georg, 210-580-9521, jgeorg@nextoncology.com
- Recruiting
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94158
Phu Lam, 415-613-2945, phu.lam@ucsf.edu
- Recruiting
Honor Health Research Institute
Scottsdale, Arizona, 85258
Christine Diab, 480-323-1350, cdiab@honorhealth.com
- Recruiting
Siteman Cancer Center
St Louis, Missouri, 63108
Alexis Cotton, 314-273-5919, a.cotton@wustl.edu
About this study
Official title: A Phase 1/2 Open-Label, Multicenter Study of RAS(ON) Inhibitors in Combination With Ivonescimab With or Without Other Anti-Cancer Agents in Patients With Solid Tumors
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of RAS(ON) inhibitors in combination with ivonescimab in adults with advanced or metastatic solid tumors with a RAS mutation.
Read the detailed description
This is an open-label, multicenter, Phase 1/2 study of RAS(ON) inhibitors in combination with ivonescimab with or without other anti-cancer agents in adults with advanced or metastatic solid tumors with a RAS mutation to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary clinical activity. The study consists of three arms: Arm A:daraxonrasib in combination with ivonescimab; Arm B: elironrasib in combination with ivonescimab; and Arm C: zoldonrasib in combination with ivonescimab. All arms consist of two parts: Part 1- dose exploration and Part 2- dose expansion. Part 1 dose exploration will explore the safety and tolerability of individual RAS(ON) inhibitors in combination with ivonescimab. Part 2 dose expansion will explore the safety, tolerability, and antitumor activity of the individual RAS(ON) inhibitors with ivonescimab +/- anti-cancer therapies.
- Conditions
- Advanced Solid Tumors, Metastatic Solid Tumors, Non-small Cell Lung Cancer (NSCLC), NSCLC, Colorectal Cancer (CRC), CRC
- Being tested
- Daraxonrasib, Elironrasib, Zoldonrasib, Ivonescimab, Carboplatin/Cisplatin + Pemetrexed (Dose Expansion Only)
- Keywords
- Advanced Solid Tumors, Metastatic Solid Tumors, Non-small Cell Lung Cancer, NSCLC, Colorectal Cancer, CRC, RAS, NRAS, KRAS, HRAS, RAS Mutation
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DaraxonrasibDrug
oral tablets
ElironrasibDrug
oral tablets
ZoldonrasibDrug
oral tablets
IvonescimabDrug
IV infusion
Carboplatin/Cisplatin + Pemetrexed (Dose Expansion Only)Drug
IV infusion
cetuximab (Cohort C2 Only)Drug
IV infusion
Carboplatin/Cisplatin + Pemetrexed (Cohort B2 Only)Drug
IV infusion
Daraxonrasib (Cohort B1 only)Drug
oral tablets
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Daraxonrasib + Ivonescimab Combination | Experimental | Dose Exploration and Dose Expansion (+ Carboplatin/Cisplatin + Pemetrexed) Receives: Drug: Daraxonrasib; Drug: Ivonescimab; Drug: Carboplatin/Cisplatin + Pemetrexed (Dose Expansion Only) |
| Arm B: Elironrasib + Ivonescimab Combination | Experimental | Dose Exploration and Dose Expansion. Dose Expansion will include two separate cohorts: Cohort B1 (+ daraxonrasib) and Cohort B2 (+ Carboplatin/Cisplatin + Pemetrexed). Receives: Drug: Elironrasib; Drug: Ivonescimab; Drug: Carboplatin/Cisplatin + Pemetrexed (Cohort B2 Only); Drug: Daraxonrasib (Cohort B1 only) |
| Arm C: Zoldonrasib + Ivonescimab Combination | Experimental | Dose Exploration and Dose Expansion. Dose Expansion will include two separate cohorts: Cohort C1 and Cohort C2 (+ Cetuximab). Receives: Drug: Zoldonrasib; Drug: Ivonescimab; Drug: cetuximab (Cohort C2 Only) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with adverse events (AEs)
Number of patients with AEs as assessed by CTCAE v5.
Measured: Up to approximately 4 years
Changes in vital signs
Number of patients with changes in vital signs.
Measured: Up to approximately 4 years
Changes in clinical laboratory test values
Number of patients with changes in clinical laboratory test values.
Measured: Up to approximately 4 years
Dose Limiting Toxicities
Number of patients with dose limiting toxicities
Measured: 28 days
Secondary outcomes (7)
Concentration of RAS(ON) inhibitors and ivonescimab
Trough and peak blood concentrations of RAS(ON) inhibitors and ivonescimab over time as applicable.
Measured: Up to Cycle 6 Day 1 (each cycle is 21 days)
Objective Response Rate (ORR)
ORR per response evaluation criteria in solid tumors (RECIST) v1.1
Measured: Up to approximately 4 years
Duration of Response (DOR)
DOR per RECIST v1.1
Measured: Up to approximately 4 years
Disease Control Rate (DCR)
DCR per RECIST v1.1
Measured: Up to approximately 4 years
Time to response (TTR)
TTR per RECIST v1.1
Measured: Up to approximately 4 years
Progression free survival (PFS)
PFS per RECIST v1.1
Measured: Up to approximately 4 years
Anti-drug Antibody (ADA) of ivonescimab
Number and percentage of patients with anti-ivonescimab antibody
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 posted9 Feb 2026
- Study start30 Jan 2026
- Primary completionMay 2029 (estimated)
- Study completionMay 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid TumorsStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 370 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Revolution Medicines, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Summit Therapeutics
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07397338
- Sponsor's protocol ID
- RMC-APEX-103
- Status last verified
- Nov 2026
- First submitted
- 2 Feb 2026
- Last updated
- 4 Nov 2026
- Results posted
- No
- Data monitoring committee
- No
- 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 Phase 1/2 Open-Label, Multicenter Study of RAS(ON) Inhibitors in Combination With Ivonescimab With or Without Other Anti-Cancer Agents in Patients With Solid Tumors
- ClinicalTrials.gov ID
- NCT07397338
- Acronym / sponsor ID
- RMC-APEX-103
- Conditions
- Advanced Solid Tumors, Metastatic Solid Tumors, Non-small Cell Lung Cancer (NSCLC), NSCLC, Colorectal Cancer (CRC), CRC
- Keywords
- Advanced Solid Tumors, Metastatic Solid Tumors, Non-small Cell Lung Cancer, NSCLC, Colorectal Cancer, CRC, RAS, NRAS
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 370 participants (estimated)
- Lead sponsor
- Revolution Medicines, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Summit Therapeutics
- Study start
- 30 Jan 2026 (actual)
- Primary completion
- May 2029 (estimated)
- Study completion
- May 2029 (estimated)
- First posted
- 9 Feb 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 safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of RAS(ON) inhibitors in combination with ivonescimab in adults with advanced or metastatic solid tumors with a RAS mutation.
Detailed description
This is an open-label, multicenter, Phase 1/2 study of RAS(ON) inhibitors in combination with ivonescimab with or without other anti-cancer agents in adults with advanced or metastatic solid tumors with a RAS mutation to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary clinical activity. The study consists of three arms: Arm A:daraxonrasib in combination with ivonescimab; Arm B: elironrasib in combination with ivonescimab; and Arm C: zoldonrasib in combination with ivonescimab. All arms consist of two parts: Part 1- dose exploration and Part 2- dose expansion. Part 1 dose exploration will explore the safety and tolerability of individual RAS(ON) inhibitors in combination with ivonescimab. Part 2 dose expansion will explore the safety, tolerability, and antitumor activity of the individual RAS(ON) inhibitors with ivonescimab +/- anti-cancer therapies.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm A: Daraxonrasib + Ivonescimab Combination | Experimental | Drug: Daraxonrasib, Drug: Ivonescimab, Drug: Carboplatin/Cisplatin + Pemetrexed (Dose Expansion Only)Dose Exploration and Dose Expansion (+ Carboplatin/Cisplatin + Pemetrexed) |
| Arm B: Elironrasib + Ivonescimab Combination | Experimental | Drug: Elironrasib, Drug: Ivonescimab, Drug: Carboplatin/Cisplatin + Pemetrexed (Cohort B2 Only), Drug: Daraxonrasib (Cohort B1 only)Dose Exploration and Dose Expansion. Dose Expansion will include two separate cohorts: Cohort B1 (+ daraxonrasib) and Cohort B2 (+ Carboplatin/Cisplatin + Pemetrexed). |
| Arm C: Zoldonrasib + Ivonescimab Combination | Experimental | Drug: Zoldonrasib, Drug: Ivonescimab, Drug: cetuximab (Cohort C2 Only)Dose Exploration and Dose Expansion. Dose Expansion will include two separate cohorts: Cohort C1 and Cohort C2 (+ Cetuximab). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- At least 18 years old and has provided informed consent.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Histologically confirmed, locally advanced or metastatic solid tumor malignancy with documented RAS mutation in KRAS, HRAS, or NRAS.
- Received and progressed or been intolerant to prior standard therapy (Part 1 Dose Exploration).
- Non-squamous NSCLC without a treatable driver mutation in other oncogenes that has not received prior systemic treatment (Arms A \& B for Part 2 Dose Expansion).
Key exclusion criteria (5 listed)
- Head and neck squamous cell carcinoma.
- Any conditions that may affect the ability to take or absorb study drug.
- Major surgery within 4 weeks prior to receiving study drug(s).
- Patient is unable or unwilling to comply with protocol-required study visits or procedures.
- Other inclusion/exclusion criteria may apply.
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 |
|---|---|---|
| Daraxonrasiboral tablets | Drug | Arm A: Daraxonrasib + Ivonescimab Combination |
| Elironrasiboral tablets | Drug | Arm B: Elironrasib + Ivonescimab Combination |
| Zoldonrasiboral tablets | Drug | Arm C: Zoldonrasib + Ivonescimab Combination |
| IvonescimabIV infusion | Drug | Arm A: Daraxonrasib + Ivonescimab Combination, Arm B: Elironrasib + Ivonescimab Combination, Arm C: Zoldonrasib + Ivonescimab Combination |
| Carboplatin/Cisplatin + Pemetrexed (Dose Expansion Only)IV infusion | Drug | Arm A: Daraxonrasib + Ivonescimab Combination |
| cetuximab (Cohort C2 Only)IV infusion | Drug | Arm C: Zoldonrasib + Ivonescimab Combination |
| Carboplatin/Cisplatin + Pemetrexed (Cohort B2 Only)IV infusion | Drug | Arm B: Elironrasib + Ivonescimab Combination |
| Daraxonrasib (Cohort B1 only)oral tablets | Drug | Arm B: Elironrasib + Ivonescimab Combination |
Primary outcome
Number of patients with adverse events (AEs)
Time frame: Up to approximately 4 years
Number of patients with AEs as assessed by CTCAE v5.
Changes in vital signs
Time frame: Up to approximately 4 years
Number of patients with changes in vital signs.
Changes in clinical laboratory test values
Time frame: Up to approximately 4 years
Number of patients with changes in clinical laboratory test values.
Dose Limiting Toxicities
Time frame: 28 days
Number of patients with dose limiting toxicities
7 secondary outcomes
Concentration of RAS(ON) inhibitors and ivonescimab
Time frame: Up to Cycle 6 Day 1 (each cycle is 21 days)
Objective Response Rate (ORR)
Time frame: Up to approximately 4 years
Duration of Response (DOR)
Time frame: Up to approximately 4 years
Disease Control Rate (DCR)
Time frame: Up to approximately 4 years
Time to response (TTR)
Time frame: Up to approximately 4 years
Progression free survival (PFS)
Time frame: Up to approximately 4 years
Anti-drug Antibody (ADA) of ivonescimab
Time frame: Up to approximately 4 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 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.
19 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Daraxonrasib, Elironrasib and Zoldonrasib in people with Advanced Solid Tumors and Metastatic Solid Tumors, run by Revolution Medicines, Inc. at 19 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 9 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: 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 19 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Number of patients with adverse events (AEs) (time frame: Up to approximately 4 years). The study lists 4 primary outcomes in all. 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.