TrialFetch AI Analysis
Goal: To determine whether ivonescimab plus mFOLFOX6 improves efficacy compared with bevacizumab plus mFOLFOX6 as first-line therapy for metastatic colorectal cancer, with progression-free survival as the primary endpoint.
Patients: Approximately 600 adults with histologically/cytologically confirmed metastatic colorectal cancer, ECOG 0–1, life expectancy at least 6 months, and at least one measurable noncerebral lesion, who have not received prior systemic therapy for metastatic disease. Key exclusions include MSI-H/dMMR tumors, known BRAF V600E mutation, resectable disease, significant GI obstruction, recent paracentesis-requiring ascites, prior immunotherapy or anti-angiogenic therapy for colorectal cancer, and active/prior inflammatory bowel disease or chronic diarrhea.
Design: Phase 3, multiregional, multicenter, randomized (1:1), active-controlled, double-blind study comparing an investigational anti–PD-1/anti-VEGF bispecific antibody regimen against a standard anti-VEGF regimen, each combined with mFOLFOX6. Treatment is administered every 2 weeks with induction followed by maintenance, with independent radiology review committee assessment per RECIST v1.1 for key efficacy endpoints.
Treatments: Experimental arm: ivonescimab plus mFOLFOX6 IV every 2 weeks for up to 8 cycles, followed by maintenance ivonescimab plus 5-FU/leucovorin every 2 weeks for up to 2 years. Control arm: bevacizumab plus mFOLFOX6 IV every 2 weeks for up to 8 cycles, followed by maintenance bevacizumab plus 5-FU/leucovorin every 2 weeks for up to 2 years. Ivonescimab (AK112/SMT112) is a first-in-class tetravalent bispecific antibody targeting PD-1 and VEGF, intended to combine immune checkpoint blockade with anti-angiogenic effects and to modulate the immunosuppressive tumor microenvironment. Its design aims for cooperative binding between VEGF and PD-1 targets, potentially enhancing activity where VEGF is present. Across earlier studies in solid tumors it demonstrated antitumor activity and a generally manageable safety profile, and in a phase 3 study in PD-L1–positive advanced NSCLC it improved progression-free survival versus pembrolizumab, supporting continued development across tumor types.
Outcomes: Primary endpoint is progression-free survival assessed by independent radiology review committee per RECIST v1.1 (followed up to ~2.5 years). Secondary endpoints include overall survival (up to ~4 years), overall response rate and duration of response by independent review per RECIST v1.1 (up to ~2.5 years), and safety including incidence and severity of adverse events and clinically significant laboratory abnormalities (captured from consent through 30 days after last dose for AEs and 90 days for related serious AEs, with longer follow-up up to ~4 years).
Burden on patient: Moderate burden. Treatment requires IV infusions every 2 weeks with combination chemotherapy during induction (up to 8 cycles) and continued every-2-week maintenance infusions for up to 2 years, which entails frequent clinic visits similar to standard first-line mFOLFOX6-based therapy. Efficacy assessment requires serial imaging for RECIST-based response and progression evaluation (frequency not specified but typically regular throughout first-line metastatic treatment). No protocol-mandated tumor biopsies or intensive pharmacokinetic sampling are described, and follow-up for survival and late toxicities extends for several years.
Last updated: Jan 2026
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