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NCT07397338PHASE1, PHASE2Recruiting

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

Revolution Medicines, Inc.

Start Date

1/30/2026

Completion Date

5/1/2029

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.

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.

Eligibility Criteria

Age Range: 18 years to No maximum

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.

Interventions

DRUG

Daraxonrasib

DRUG

Elironrasib

DRUG

Zoldonrasib

DRUG

Ivonescimab

DRUG

Carboplatin/Cisplatin + Pemetrexed (Dose Expansion Only)

DRUG

cetuximab (Cohort C2 Only)

DRUG

Carboplatin/Cisplatin + Pemetrexed (Cohort B2 Only)

DRUG

Daraxonrasib (Cohort B1 only)

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Conditions

Advanced Solid TumorsMetastatic Solid TumorsNon-small Cell Lung Cancer (NSCLC)NSCLCColorectal Cancer (CRC)CRC

Locations

Eastern Connecticut Hematology and Oncology Associates

Norwich, Connecticut 06360

United States

Tennessee Oncology

Nashville, Tennessee 37023

United States

MD Anderson Cancer Center

Houston, Texas 77030

United States

NEXT Dallas

Irving, Texas 75039

United States

NEXT Oncology

San Antonio, Texas 78229

United States

NEXT Virginia

Fairfax, Virginia 22031

United States