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

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
370

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Revolution Medicines, Inc.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 30, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 1, 2029

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 1, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 2, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 2, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 9, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 12, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 11, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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