Phase 1/2 ivonescimab PD-1×VEGF-A bispecific antibody with platinum chemo + SRS in NSCLC brain mets.

This Memorial Sloan Kettering–sponsored Phase 1/2 study tests ivonescimab (AK112/SMT112)—a tetravalent bispecific antibody that blocks PD-1 on T cells and neutralizes VEGF-A to combine immune checkpoint inhibition with anti-angiogenic signaling—in patients with non-small cell lung cancer that has metastasized to the brain. Phase 1 is a dose-escalation safety run-in where ivonescimab is given with standard chemotherapy on cycle 1 day 1, followed by fractionated stereotactic radiosurgery (9 Gy × 3 fractions) typically starting days 7–10, then continued systemic therapy after a day-21 toxicity check; Phase 2 expands at the recommended Phase 2 dose to better estimate intracranial activity and tolerability. The commercial/scientific angle is the “triple-modality” strategy (PD-1 + VEGF + focal RT) aimed at improving intracranial control while maintaining systemic disease coverage—leveraging ivonescimab’s dual-target design originated at Akeso and licensed ex-China to Summit Therapeutics. Today, many NSCLC brain-met patients receive SRS (or surgery when feasible) plus systemic therapy selected by biomarkers (targeted TKIs for actionable drivers; otherwise platinum chemo + PD-1/PD-L1 immunotherapy), with WBRT reserved for selected diffuse cases.