A Randomized, Active-Controlled, Double-blind, Multicenter, Phase 3 Clinical Study of Ivonescimab in Combination with FOLFOX versus Bevacizumab in Combination with FOLFOX for the First-line Treatment of Metastatic Colorectal Cancer (HARMONi-GI3)

Prior treatment

• Known BRAF V600E mutation status. known DPD deficiency (refer to local fluorouracil label or local clinical guidance for DPD status recommendation prior to starting treatment).
• Patients who have received prior immunotherapy or anti-angiogenic therapy for colorectal cancer, including immune checkpoint inhibitors, immune checkpoint agonists, immune cell therapy and any other therapy based on the mechanism of action of tumor immunity or angiogenesis
• Symptomatic central nervous system (CNS) metastases with hemorrhagic features, CNS metastasis ≥ 1.5 cm, CNS radiation within 7 days prior to randomization, potential need for CNS radiation within the first cycle, or leptomeningeal disease. NOTE:- Patients who have stopped corticosteroids or on stable corticosteroid therapy (prednisone ≤ 10 mg daily or equivalent) are allowed.

Other illness

• Resectable oligometastastic-only disease with multidisciplinary plan for complete resection of all disease.

Lab values

• Patients with known MSI-H/dMMR disease as determined by a health authority approved assay (eg, FDA for United States, CE-IVD marked for Europe, PMDA for Japan, and NMPA for China) conducted at a local clinical laboratory or at the central laboratory.

Other

• Ascites requiring paracentesis within last 30 days.

• Histologically or cytologically confirmed mCRC, not amenable to curative resection.
• An Eastern Cooperative Oncology Organization Group (ECOG) performance status score of 0 or 1.
• No prior systemic therapy for mCRC. NOTE:- If patients have received systemic therapy or radiotherapy for early-stage disease, >12 months must have elapsed since completion of neoadjuvant therapy and/or adjuvant therapy (including adjuvant oxaliplatin or radiotherapy) and prior to diagnosis of recurrent or metastatic disease.
• At least one measurable tumor lesion according to RECIST v1.1 that is amenable to repeated accurate measurements. NOTE:- Brain metastases cannot be selected as target lesions and lesions that have received radiotherapy in the past cannot be selected as target lesions unless they have progressed following radiation
• Known BRAF, KRAS and NRAS (extended RAS) mutation status from existing reports, or determined by testing tumor tissue utilizing a clinical assay.