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
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Revolution Medicines, Inc.
- Enrollment
- 370
- Locations
- 8
- Primary Endpoint
- Number of patients with adverse events (AEs)
Study Overview
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.
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 Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •At least 18 years old and has provided informed consent.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •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.
Arms & Interventions
Arm A: Daraxonrasib + Ivonescimab Combination
Dose Exploration and Dose Expansion (+ Carboplatin/Cisplatin + Pemetrexed)
Intervention: Carboplatin/Cisplatin + Pemetrexed (Dose Expansion Only) (Drug)
Arm A: Daraxonrasib + Ivonescimab Combination
Dose Exploration and Dose Expansion (+ Carboplatin/Cisplatin + Pemetrexed)
Intervention: Daraxonrasib (Drug)
Arm A: Daraxonrasib + Ivonescimab Combination
Dose Exploration and Dose Expansion (+ Carboplatin/Cisplatin + Pemetrexed)
Intervention: Ivonescimab (Drug)
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).
Intervention: Ivonescimab (Drug)
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).
Intervention: Elironrasib (Drug)
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).
Intervention: Daraxonrasib (Cohort B1 only) (Drug)
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).
Intervention: Carboplatin/Cisplatin + Pemetrexed (Cohort B2 Only) (Drug)
Arm C: Zoldonrasib + Ivonescimab Combination
Dose Exploration and Dose Expansion. Dose Expansion will include two separate cohorts: Cohort C1 and Cohort C2 (+ Cetuximab).
Intervention: Ivonescimab (Drug)
Arm C: Zoldonrasib + Ivonescimab Combination
Dose Exploration and Dose Expansion. Dose Expansion will include two separate cohorts: Cohort C1 and Cohort C2 (+ Cetuximab).
Intervention: Zoldonrasib (Drug)
Arm C: Zoldonrasib + Ivonescimab Combination
Dose Exploration and Dose Expansion. Dose Expansion will include two separate cohorts: Cohort C1 and Cohort C2 (+ Cetuximab).
Intervention: cetuximab (Cohort C2 Only) (Drug)
Outcomes
Primary Outcomes
Number of patients with adverse events (AEs)
Time Frame: Up to approximately 4 years
Number of patients with AEs as assessed by CTCAE v5.
Changes in vital signs
Time Frame: Up to approximately 4 years
Number of patients with changes in vital signs.
Changes in clinical laboratory test values
Time Frame: Up to approximately 4 years
Number of patients with changes in clinical laboratory test values.
Dose Limiting Toxicities
Time Frame: 28 days
Number of patients with dose limiting toxicities
Secondary Outcomes
- 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)
- Progression free survival (PFS)(Up to approximately 4 years)
- Anti-drug Antibody (ADA) of ivonescimab(Up to approximately 4 years)