Combining RAS(ON) inhibitors with ivonescimab for adults with RAS‑mutant advanced solid tumors

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This open‑label, multicenter Phase 1/2 trial tests three different RAS(ON) inhibitors (daraxonrasib, elironrasib, zoldonrasib) each given with the monoclonal antibody ivonescimab in adults with RAS‑mutant advanced or metastatic solid tumors. Each arm includes a Part 1 dose‑finding stage to explore safety, tolerability, and pharmacokinetics, followed by a Part 2 dose‑expansion stage to look for antitumor activity and further safety signals, with some expansions allowing additional anti‑cancer agents such as platinum/pemetrexed chemotherapy. Primary outcomes include safety, tolerability, and drug exposure, and secondary assessments include preliminary tumor responses measured by RECIST v1.1. Enrollment criteria and prior‑treatment limits differ by arm and cohort (for example, certain expansions enroll treatment‑naive non‑squamous NSCLC or colorectal/solid tumors after limited prior lines of therapy).

Why it matters

Who can join: the full rules

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.

Where it's running

• Honor Health Research Institute
  Scottsdale, Arizona, United States Recruiting
• USC Norris Comprehensive Cancer Center
  Los Angeles, California, United States Recruiting
• UCSF Helen Diller Family Comprehensive Cancer Center
  San Francisco, California, United States Recruiting
• Eastern Connecticut Hematology and Oncology Associates
  Norwich, Connecticut, United States Recruiting
• University of Kentucky HealthCare (UK HealthCare)
  Lexington, Kentucky, United States Recruiting
• Health Partners Cancer Center at Regions Hospital
  Saint Paul, Minnesota, United States Recruiting

Study contacts

• Study coordinator: Revolution Medicines Study Director
• Email: medinfo@revmed.com
• Phone: 1-844-2-REVMED

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

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• Targeted alpha therapy for B7-H3 expressing solid tumors using AKY-2519

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.