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Study of RAS(ON) Inhibitors in Combination With Ivonescimab in Patients With Solid Tumors
NCT07397338 · Revolution Medicines, Inc.
In plain English
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Official title
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
About this study
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
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 design
Enrollment target: 370 participants
Allocation: non_randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2026-01-30
Estimated completion: 2029-05
Last updated: 2026-03-30
Interventions
Drug: DaraxonrasibDrug: ElironrasibDrug: ZoldonrasibDrug: IvonescimabDrug: Carboplatin/Cisplatin + Pemetrexed (Dose Expansion Only)Drug: cetuximab (Cohort C2 Only)Drug: Carboplatin/Cisplatin + Pemetrexed (Cohort B2 Only)Drug: Daraxonrasib (Cohort B1 only)
Primary outcomes
- • Number of patients with adverse events (AEs) (Up to approximately 4 years)
- • Changes in vital signs (Up to approximately 4 years)
- • Changes in clinical laboratory test values (Up to approximately 4 years)
Sponsor
Revolution Medicines, Inc. · industry
With: Summit Therapeutics
Contacts & investigators
ContactRevolution Medicines Study Director · contact · medinfo@revmed.com · 1-844-2-REVMED
All locations (5)
Eastern Connecticut Hematology and Oncology AssociatesRecruiting
Norwich, Connecticut, United States
Tennessee OncologyRecruiting
Nashville, Tennessee, United States
NEXT DallasRecruiting
Irving, Texas, United States
NEXT OncologyRecruiting
San Antonio, Texas, United States
NEXT VirginiaRecruiting
Fairfax, Virginia, United States