Akeso’s ivonescimab tops Imfinzi in fifth straight positive Phase III readout

A randomized Phase III trial in China has produced the first known overall survival superiority result over an anti-PD-(L)1 plus chemotherapy regimen in advanced biliary tract cancer (BTC). China-based Akeso Inc. (HKEX: 9926.HK) reported that ivonescimab plus chemotherapy achieved statistically significant and clinically meaningful superiority over AstraZeneca's Imfinzi (durvalumab) plus chemotherapy in the primary endpoint of overall survival at a pre-specified interim analysis of the HARMONi-GI1 study (AK112-309). Key secondary endpoints of progression-free survival and objective response rate were also met. No numerical data have been disclosed; full results are expected at an upcoming medical congress.

Ivonescimab is a bispecific antibody that simultaneously blocks PD-1 and VEGF within a single tetravalent molecule. The molecule is approved in China for multiple non-small cell lung cancer (NSCLC) indications, and the HARMONi-GI1 readout is its first Phase III result outside NSCLC.

The result carries particular weight in BTC because the two approved first-line immunotherapy combinations — durvalumab plus gemcitabine/cisplatin (GemCis), approved by the FDA in September 2022, and Merck's Keytruda (pembrolizumab) plus GemCis, approved in October 2023 — each demonstrated statistically significant but modest OS gains over chemotherapy alone in unselected populations. No prior Phase III study has shown superiority over an anti-PD-(L)1 plus chemotherapy backbone in this disease. Akeso described HARMONi-GI1 as the first known study to cross that threshold.

The trial is single-region, conducted and sponsored by Akeso in China, with all data generated and analyzed by Akeso. Summit Therapeutics Inc. (Nasdaq: SMMT), which holds ivonescimab rights in North America, Europe, and other territories outside China, noted the result but does not sponsor the study. Ivonescimab remains investigational and unapproved in Summit's license territories.

For Summit, the BTC readout arrives as the company awaits an FDA decision on a separate Biologics License Application for ivonescimab plus chemotherapy in EGFR-mutant non-squamous NSCLC post-TKI therapy, with a PDUFA date of November 14, 2026. The BTC data add to a now five-study run of positive Phase III readouts for ivonescimab, four in NSCLC and one in BTC — all with Akeso-reported statistically significant results, including OS superiority in squamous NSCLC versus tislelizumab presented at ASCO 2026 and an NMPA approval for that indication in August 2026.

The absence of numerical data limits interpretation. Cross-trial comparisons with TOPAZ-1 (durvalumab) or KEYNOTE-966 (pembrolizumab) are not possible until hazard ratios, medians, and confidence intervals are reported. HARMONi-GI1 used an active comparator — durvalumab plus chemotherapy rather than chemotherapy alone — which represents a higher evidentiary bar than the placebo-controlled designs that established the current standard of care, but the single-region conduct in China and the lack of published data mean the global applicability of the result will require further scrutiny.

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