Study of RAS(ON) Inhibitors in Combination With Ivonescimab in Patients With Solid Tumors

May 11, 2026 updated by: Revolution Medicines, Inc.

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

370

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

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

Study Locations

  • United States
    • Connecticut
      • Norwich, Connecticut, United States, 06360
        • Recruiting
        • Eastern Connecticut Hematology and Oncology Associates
        • Contact:
    • Tennessee
      • Nashville, Tennessee, United States, 37023
    • Texas
      • Irving, Texas, United States, 75039
      • San Antonio, Texas, United States, 78229
    • Virginia
      • Fairfax, Virginia, United States, 22031

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A: Daraxonrasib + Ivonescimab Combination
Dose Exploration and Dose Expansion (+ Carboplatin/Cisplatin + Pemetrexed)
Drug: Daraxonrasib
oral tablets
Drug: Ivonescimab
IV infusion
Drug: Carboplatin/Cisplatin + Pemetrexed (Dose Expansion Only)
IV infusion
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).
Drug: Ivonescimab
IV infusion
Drug: Elironrasib
oral tablets
Drug: Carboplatin/Cisplatin + Pemetrexed (Cohort B2 Only)
IV infusion
Drug: Daraxonrasib (Cohort B1 only)
oral tablets
Experimental: Arm C: Zoldonrasib + Ivonescimab Combination
Dose Exploration and Dose Expansion. Dose Expansion will include two separate cohorts: Cohort C1 and Cohort C2 (+ Cetuximab).
Drug: Ivonescimab
IV infusion
Drug: Zoldonrasib
oral tablets
Drug: cetuximab (Cohort C2 Only)
IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients with adverse events (AEs)
Time Frame: Up to approximately 4 years
Number of patients with AEs as assessed by CTCAE v5.
Up to approximately 4 years
Changes in vital signs
Time Frame: Up to approximately 4 years
Number of patients with changes in vital signs.
Up to approximately 4 years
Changes in clinical laboratory test values
Time Frame: Up to approximately 4 years
Number of patients with changes in clinical laboratory test values.
Up to approximately 4 years
Dose Limiting Toxicities
Time Frame: 28 days
Number of patients with dose limiting toxicities
28 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Concentration of RAS(ON) inhibitors and ivonescimab
Time Frame: Up to Cycle 6 Day 1 (each cycle is 21 days)
Trough and peak blood concentrations of RAS(ON) inhibitors and ivonescimab over time as applicable.
Up to Cycle 6 Day 1 (each cycle is 21 days)
Objective Response Rate (ORR)
Time Frame: Up to approximately 4 years
ORR per response evaluation criteria in solid tumors (RECIST) v1.1
Up to approximately 4 years
Duration of Response (DOR)
Time Frame: Up to approximately 4 years
DOR per RECIST v1.1
Up to approximately 4 years
Disease Control Rate (DCR)
Time Frame: Up to approximately 4 years
DCR per RECIST v1.1
Up to approximately 4 years
Time to response (TTR)
Time Frame: Up to approximately 4 years
TTR per RECIST v1.1
Up to approximately 4 years
Progression free survival (PFS)
Time Frame: Up to approximately 4 years
PFS per RECIST v1.1
Up to approximately 4 years
Anti-drug Antibody (ADA) of ivonescimab
Time Frame: Up to approximately 4 years
Number and percentage of patients with anti-ivonescimab antibody
Up to approximately 4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Revolution Medicines, Inc.

Collaborators

Summit Therapeutics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 30, 2026

Primary Completion (Estimated)

May 1, 2029

Study Completion (Estimated)

May 1, 2029

Study Registration Dates

First Submitted

February 2, 2026

First Submitted That Met QC Criteria

February 2, 2026

First Posted (Actual)

February 9, 2026

Study Record Updates

Last Update Posted (Actual)

May 12, 2026

Last Update Submitted That Met QC Criteria

May 11, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RMC-APEX-103

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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