Ivonescimab (PD-1×VEGF bispecific) + mFOLFOX6 posts 70.8% ORR and 100% DCR in 1L unresectable mCRC (Phase 2)

Ivonescimab is an investigational tetrameric bispecific antibody co-targeting PD-1 and VEGF, here combined with oxaliplatin/5-FU/leucovorin (mFOLFOX6) as first-line therapy in a multiregional Phase 2 trial (NCT05382442) enrolling untreated unresectable mCRC in China and the US (n=49; 20 mg/kg n=25, 10 mg/kg n=24; data cutoff December 31, 2025). With 7-month median follow-up, ORR was 70.8% in both arms (all partial responses) and DCR was 100%; median PFS was not reached, with 6-month PFS rates of 95.2% (20 mg/kg) and 84.8% (10 mg/kg)—numerically above typical first-line mFOLFOX6 ± bevacizumab ORR (50–60% range in older datasets) but still early and single-study, with no randomized SOC comparator here. Grade ≥3 ivo-related TEAEs occurred in 40.0% vs 33.3%, serious ivo-related TEAEs in 24.0% vs 16.7%, and ivo discontinuation due to TEAEs was 4.0% vs 0% (no TEAE-related deaths), suggesting meaningful added toxicity that will need to be weighed against benefit versus established chemo±VEGF strategies.