NCT07397338

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
370

participants targeted

Target at P75+ for phase_1

Timeline
36mo left

Started Jan 2026

Typical duration for phase_1

Geographic Reach
1 country

5 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress10%
Jan 2026May 2029

Study Start

First participant enrolled

January 30, 2026

Completed
3 days until next milestone

First Submitted

Initial submission to the registry

February 2, 2026

Completed
7 days until next milestone

First Posted

Study publicly available on registry

February 9, 2026

Completed
3.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2029

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2029

Last Updated

May 12, 2026

Status Verified

May 1, 2026

Enrollment Period

3.3 years

First QC Date

February 2, 2026

Last Update Submit

May 11, 2026

Conditions

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

Keywords

Advanced Solid TumorsMetastatic Solid TumorsNon-small Cell Lung CancerNSCLCColorectal CancerCRCRASNRASKRASHRASRAS Mutation

Outcome Measures

Primary Outcomes (4)

  • Number of patients with adverse events (AEs)

    Number of patients with AEs as assessed by CTCAE v5.

    Up to approximately 4 years

  • Changes in vital signs

    Number of patients with changes in vital signs.

    Up to approximately 4 years

  • Changes in clinical laboratory test values

    Number of patients with changes in clinical laboratory test values.

    Up to approximately 4 years

  • Dose Limiting Toxicities

    Number of patients with dose limiting toxicities

    28 days

Secondary Outcomes (7)

  • Concentration of RAS(ON) inhibitors and ivonescimab

    Up to Cycle 6 Day 1 (each cycle is 21 days)

  • Objective Response Rate (ORR)

    Up to approximately 4 years

  • Duration of Response (DOR)

    Up to approximately 4 years

  • Disease Control Rate (DCR)

    Up to approximately 4 years

  • Time to response (TTR)

    Up to approximately 4 years

  • +2 more secondary outcomes

Study Arms (3)

Arm A: Daraxonrasib + Ivonescimab Combination

EXPERIMENTAL

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

Drug: DaraxonrasibDrug: IvonescimabDrug: Carboplatin/Cisplatin + Pemetrexed (Dose Expansion Only)

Arm B: Elironrasib + Ivonescimab Combination

EXPERIMENTAL

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

Drug: ElironrasibDrug: IvonescimabDrug: Carboplatin/Cisplatin + Pemetrexed (Cohort B2 Only)Drug: Daraxonrasib (Cohort B1 only)

Arm C: Zoldonrasib + Ivonescimab Combination

EXPERIMENTAL

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

Drug: ZoldonrasibDrug: IvonescimabDrug: cetuximab (Cohort C2 Only)

Interventions

DaraxonrasibDRUG

oral tablets

Arm A: Daraxonrasib + Ivonescimab Combination
Daraxonrasib (Cohort B1 only)DRUG

oral tablets

Arm B: Elironrasib + Ivonescimab Combination
ElironrasibDRUG

oral tablets

Arm B: Elironrasib + Ivonescimab Combination
cetuximab (Cohort C2 Only)DRUG

IV infusion

Arm C: Zoldonrasib + Ivonescimab Combination
Carboplatin/Cisplatin + Pemetrexed (Cohort B2 Only)DRUG

IV infusion

Arm B: Elironrasib + Ivonescimab Combination
Carboplatin/Cisplatin + Pemetrexed (Dose Expansion Only)DRUG

IV infusion

Arm A: Daraxonrasib + Ivonescimab Combination
ZoldonrasibDRUG

oral tablets

Arm C: Zoldonrasib + Ivonescimab Combination
IvonescimabDRUG

IV infusion

Arm A: Daraxonrasib + Ivonescimab CombinationArm B: Elironrasib + Ivonescimab CombinationArm C: Zoldonrasib + Ivonescimab Combination

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Eastern Connecticut Hematology and Oncology Associates

Norwich, Connecticut, 06360, United States

RECRUITING

Tennessee Oncology

Nashville, Tennessee, 37023, United States

RECRUITING

NEXT Dallas

Irving, Texas, 75039, United States

RECRUITING

NEXT Oncology

San Antonio, Texas, 78229, United States

RECRUITING

NEXT Virginia

Fairfax, Virginia, 22031, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell LungColorectal Neoplasms

Interventions

CarboplatinCisplatinPemetrexedCetuximab

Condition Hierarchy (Ancestors)

Carcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteNeoplasmsLung DiseasesRespiratory Tract DiseasesIntestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsDigestive System DiseasesGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesRectal Diseases

Intervention Hierarchy (Ancestors)

Coordination ComplexesOrganic ChemicalsChlorine CompoundsInorganic ChemicalsNitrogen CompoundsPlatinum CompoundsGuanineHypoxanthinesPurinonesPurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsGlutamatesAmino Acids, AcidicAmino AcidsAmino Acids, Peptides, and ProteinsAmino Acids, DicarboxylicAntibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsSerum GlobulinsGlobulins

Central Study Contacts

Revolution Medicines Study Director

CONTACT

1-844-2-REVMEDmedinfo@revmed.com

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 2, 2026

First Posted

February 9, 2026

Study Start

January 30, 2026

Primary Completion (Estimated)

May 1, 2029

Study Completion (Estimated)

May 1, 2029

Last Updated

May 12, 2026

Record last verified: 2026-05

Locations

US(5)