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

Revolution Medicines

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Non-small Cell Lung Cancer (NSCLC); Colorectal Cancer (CRC); Advanced Solid Tumors; CRC; Metastatic Solid Tumors; NSCLC

Treatments: Drug: Carboplatin/Cisplatin + Pemetrexed (Cohort B2 Only); Drug: Daraxonrasib; Drug: cetuximab (Cohort C2 Only); Drug: Daraxonrasib (Cohort B1 only); Drug: Zoldonrasib; Drug: Elironrasib; Drug: Ivonescimab; Drug: Carboplatin/Cisplatin + Pemetrexed (Dose Expansion Only)

Study type: Interventional

Funder types: Industry

Identifiers

NCT07397338

RMC-APEX-103

Details and patient eligibility

About

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.

Full 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.

Enrollment: 370 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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370 participants in 3 patient groups

Arm A: Daraxonrasib + Ivonescimab Combination

Experimental group

Description:

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

Treatment:

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

Drug: Ivonescimab

Drug: Daraxonrasib

Arm B: Elironrasib + Ivonescimab Combination

Experimental group

Description:

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

Treatment:

Drug: Ivonescimab

Drug: Elironrasib

Drug: Daraxonrasib (Cohort B1 only)

Drug: Carboplatin/Cisplatin + Pemetrexed (Cohort B2 Only)

Arm C: Zoldonrasib + Ivonescimab Combination

Experimental group

Description:

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

Treatment:

Drug: Ivonescimab

Drug: Zoldonrasib

Drug: cetuximab (Cohort C2 Only)