China-based Akeso has reported that ivonescimab, its proprietary PD-1×VEGF bispecific antibody (BsAb), combined with chemotherapy met the overall survival (OS) primary endpoint with statistical significance and clinically meaningful benefit in the Phase III AK112-309/HARMONi-GI1 study in first-line advanced biliary tract cancer, while also hitting all key secondary endpoints of progression-free survival (PFS) and objective response rate (ORR) versus durvalumab plus chemotherapy, the current globally recognised optimal standard of care.

The randomised, double-blind, multicentre Chinese registration trial is the first Phase III in biliary tract cancer to show an OS advantage head-to-head against a PD-L1 antibody plus chemo, extending ivonescimab's winning streak to three Phase III wins after HARMONi-2 versus pembrolizumab in PD-L1-positive NSCLC (median PFS 11.14 vs 5.8 months) and HARMONi-6 versus tislelizumab in squamous NSCLC (OS 27.9 vs 23.7 months).

Ivonescimab, out-licensed to Summit Therapeutics in ex-China markets in a 2022 deal valued at up to USD 5 billion upfront plus royalties and equity, now holds over 16 Phase III programmes globally, including 6 international multicentre registration trials and 7 head-to-head studies against PD-(L)1 agents across lung, colorectal, head and neck, triple-negative breast, pancreatic, and urothelial cancers. The biliary tract result converts a lung-centric IO 2.0 narrative into a gastro-intestinal tumour validation.