Recruiting
Phase 1
Phase 2

RAS(ON) Inhibitors & Ivonescimab

Sponsor:

Revolution Medicines, Inc.

Code:

NCT07397338

Conditions

Advanced Solid Tumors

Metastatic Solid Tumors

Non-small Cell Lung Cancer (NSCLC)

NSCLC

Colorectal Cancer (CRC)

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Daraxonrasib

Elironrasib

Zoldonrasib

Ivonescimab

Carboplatin/Cisplatin + Pemetrexed (Dose Expansion Only)

Study Details

Brief 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.

Conditions

Advanced Solid Tumors

Metastatic Solid Tumors

Non-small Cell Lung Cancer (NSCLC)

NSCLC

Colorectal Cancer (CRC)

Study ID

NCT07397338

Start date

Jan 30, 2026

Status verified date

Jul, 2026

Completion date

May, 2029

Anticipated

Primary completion date

May, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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).
  • Measurable disease per RECIST v1.1
  • Adequate organ function (bone marrow, liver, kidney, coagulation, endocrine).
  • Able to take oral medications.

Exclusion Criteria:

  • 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.

Study Design

Enrollment

370 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm A: Daraxonrasib + Ivonescimab Combination

Dose Exploration and Dose Expansion (+ Carboplatin/Cisplatin + Pemetrexed)

experimental: Arm B: Elironrasib + Ivonescimab Combination

Dose Exploration and Dose Expansion. Dose Expansion will include two separate cohorts: Cohort B1 (+ daraxonrasib) and Cohort B2 (+ Carboplatin/Cisplatin + Pemetrexed).

experimental: Arm C: Zoldonrasib + Ivonescimab Combination

Dose Exploration and Dose Expansion. Dose Expansion will include two separate cohorts: Cohort C1 and Cohort C2 (+ Cetuximab).

Interventions

Daraxonrasib

oral tablets

Elironrasib

oral tablets

Zoldonrasib

oral tablets

Ivonescimab

IV infusion

Carboplatin/Cisplatin + Pemetrexed (Dose Expansion Only)

IV infusion

cetuximab (Cohort C2 Only)

IV infusion

Carboplatin/Cisplatin + Pemetrexed (Cohort B2 Only)

IV infusion

Daraxonrasib (Cohort B1 only)

oral tablets

Primary outcome measure

  • Number of patients with adverse events (AEs) [ Time Frame: Up to approximately 4 years ]
  • Changes in vital signs [ Time Frame: Up to approximately 4 years ]
  • Changes in clinical laboratory test values [ Time Frame: Up to approximately 4 years ]
  • Dose Limiting Toxicities [ Time Frame: 28 days ]

Central Contacts and Locations

Central contacts

Revolution Medicines Study Director

1-844-2-REVMEDmedinfo@revmed.com

Locations

USC Norris Comprehensive Cancer Center

Recruiting

Los Angeles, California, United States, 90033

Contacts

Lorraine Martinez Seng, RN

323-865-0967Lorraine.Martinez@med.usc.edu

Eastern Connecticut Hematology and Oncology Associates

Recruiting

Norwich, Connecticut, United States, 06360

Contacts

Spiro Curis

860-886-8362Scuris@echoct.com

Health Partners Cancer Center at Regions Hospital

Recruiting

Saint Paul, Minnesota, United States, 55101

Contacts

Lisa Wahowske

651-254-1517Lisa.A.Wahowske@HealthPartners.com

Tennessee Oncology

Recruiting

Nashville, Tennessee, United States, 37023

Contacts

Henry Black

615-879-6410hblack@tnonc.com

MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Contacts

Ly Nguyen

832-794-3672LMNguyen1@mdanderson.org

MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Contacts

Ly M. Nguyen

832-794-3672LMNguyen1@mdanderson.org

NEXT Dallas

Recruiting

Irving, Texas, United States, 75039

Contacts

Mofopefoluwa "Fope" Akinwale

972-893-8800fakinwale@nextoncology.com

NEXT Oncology

Recruiting

San Antonio, Texas, United States, 78229

Contacts

Jordan Georg

210-580-9521jgeorg@nextoncology.com

NEXT Virginia

Recruiting

Fairfax, Virginia, United States, 22031

Contacts

Maybelle De La Rosa

703-783-4518mdelarosa@nextoncology.com

More Information

Sponsor

Revolution Medicines, Inc.

Last update posted

Aug 3, 2026

Last verified

Jul, 2026

Keywords

  • Advanced Solid Tumors
  • Metastatic Solid Tumors
  • Non-small Cell Lung Cancer
  • NSCLC
  • Colorectal Cancer
  • CRC
  • RAS
  • NRAS
  • KRAS
  • HRAS
  • RAS Mutation

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Revolution Medicines, Inc. on 2026-08-03.