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

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.

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.