Akeso's Ivonescimab Beats Durvalumab on Overall Survival in Phase 3 Biliary Tract Cancer Trial

Akeso announced that a pre-specified interim analysis of the phase 3 HARMONi-GI1 trial (AK112-309), assessed by an independent data monitoring committee, showed ivonescimab plus chemotherapy met its primary endpoint of overall survival (OS) against durvalumab plus chemotherapy in first-line advanced biliary tract cancer (BTC), achieving a statistically significant and clinically meaningful result.¹ The trial also met all key secondary endpoints of progression-free survival and objective response rate.¹ This is the first phase 3 readout for ivonescimab in a solid tumor type outside non-small cell lung cancer (NSCLC), following four earlier positive phase 3 results in that setting.¹

How does ivonescimab work, and what is significant about this comparison?

Ivonescimab (AK112) is a bispecific antibody built on Akeso's Tetrabody platform that simultaneously targets PD-1 and VEGF, combining immune checkpoint blockade with anti-angiogenic activity in a single molecule.¹ Durvalumab, a PD-L1 monoclonal antibody, plus chemotherapy is currently the internationally recommended first-line immunotherapy standard of care for BTC.¹ Akeso states HARMONi-GI1 is the first phase 3 study in BTC to show statistically significant OS superiority against that PD-1/L1-based global standard.¹ Ivonescimab has shown this same head-to-head pattern before: in the Phase 3 HARMONi-6 trial in squamous NSCLC, the combination reduced risk of death by 34% compared with a PD-1 inhibitor plus chemotherapy, a result BioPharm International^© covered in detail.³ Phase 1b/2 data in BTC previously showed an objective response rate of 63.6%, disease control rate of 100%, median progression-free survival of 8.5 months, and median overall survival of 16.8 months, results BioPharm International reported on when ivonescimab received Breakthrough Therapy Designation from China's NMPA in this setting earlier this year.⁴

"We are delighted the Phase III clinical study of ivonescimab in combination with chemotherapy versus durvalumab in combination with chemotherapy for the first-line treatment of biliary tract cancer has achieved a statistically significant positive OS result. This is a major breakthrough for the treatment of biliary tract cancer," said Michelle Xia, founder, chairwoman, president and CEO of Akeso in a company press release. "The positive result of HARMONi-GI1 marks the first positive Phase III study for ivonescimab in gastrointestinal tumors, following four positive Phase III results in lung cancer. The breakthrough clinical value of ivonescimab is now expanding from lung cancer to a broader range of solid tumors."¹

What hasn't been disclosed yet?

This announcement reports only topline interim results; specific survival figures, hazard ratios, and full safety data have not been released.¹ Akeso states detailed results will be presented at an upcoming international academic conference and published in a peer-reviewed journal.¹ HARMONi-GI1 is also a single-region trial conducted entirely in China, with all data generated, managed, and analyzed by Akeso, a detail that matters for how the results may eventually translate to global regulatory filings.⁵

Who holds rights to ivonescimab outside China?

Summit Therapeutics holds ex-China development and commercialization rights to ivonescimab, marketed as SMT112 in its licensed territories including the US, Canada, Europe, and Japan.⁵ Summit separately acknowledged Akeso's announcement, noting this is the fifth of six registrational phase 3 ivonescimab trials to read out, and the first with a positive result outside NSCLC.⁵

What's next?

Full HARMONi-GI1 data are expected at an upcoming international conference and in a peer-reviewed publication, which will provide the specific efficacy and safety figures needed to assess the magnitude of benefit and inform any future regulatory filings.¹

References

1. Ivonescimab plus chemotherapy demonstrates significant overall survival benefit versus durvalumab plus chemotherapy in first-line biliary tract cancer: HARMONi-GI1 meets primary endpoint. News release. Akeso, Inc.; August 25, 2026. Accessed August 26, 2026.
2. The benefit of technological advancements to BsAb development. BioPharm International. Accessed August 26, 2026.
3. Ivonescimab improves overall survival in Phase 3 HARMONi-6 trial for squamous NSCLC. BioPharm International. Accessed August 26, 2026.
4. Ivonescimab breakthrough designation highlights progress in BTC treatment. BioPharm International. Published February 20, 2026. Accessed August 26, 2026.
5. Summit, Akeso tout biliary cancer win for PD-1/VEGF in China—but details are pending. BioSpace. Published August 26, 2026. Accessed August 26, 2026.