Akeso’s Ivonescimab Beats Durvalumab Standard in Phase 3 Biliary Tract Cancer Trial
Akeso’s PD-1/VEGF bispecific antibody ivonescimab has delivered another major Phase 3 victory, this time outside lung cancer, demonstrating a statistically significant overall survival advantage over durvalumab plus chemotherapy in first-line advanced biliary tract cancer.
Chinese biotechnology company Akeso announced positive topline results from the Phase 3 HARMONi-GI1 (AK112-309) trial evaluating ivonescimab plus chemotherapy as a first-line treatment for advanced biliary tract cancer (BTC).
At a prespecified interim analysis conducted by an Independent Data Monitoring Committee (IDMC), ivonescimab plus chemotherapy achieved a statistically significant and clinically meaningful improvement in overall survival (OS) compared with durvalumab plus chemotherapy, meeting the trial’s primary endpoint.
The study also met all key secondary efficacy endpoints, including progression-free survival (PFS) and objective response rate (ORR).
Akeso said detailed efficacy and safety results will be presented at an upcoming medical conference and submitted for publication in a peer-reviewed journal.
Going Head-to-Head With an Established Standard
What makes HARMONi-GI1 particularly significant is the comparator.
Rather than testing ivonescimab against chemotherapy alone, Akeso challenged an established immunotherapy-based standard of care: durvalumab plus chemotherapy.
Durvalumab, AstraZeneca’s PD-L1 inhibitor marketed as Imfinzi, became an important first-line treatment for advanced biliary tract cancer following the landmark TOPAZ-1 trial.
TOPAZ-1 demonstrated that adding durvalumab to gemcitabine plus cisplatin improved overall survival compared with chemotherapy alone. The trial reported median OS of 12.8 months versus 11.5 months, corresponding to a hazard ratio of 0.80. The results subsequently supported the FDA approval of durvalumab plus gemcitabine and cisplatin for unresectable or metastatic biliary tract cancer.
Longer-term follow-up has continued to support the durability of the durvalumab regimen. A 2026 analysis published in JAMA Oncology reported median OS of 13.0 months with durvalumab plus GemCis versus 11.4 months with placebo plus GemCis, with 11.8% of durvalumab-treated patients alive at four years.
Against that backdrop, demonstrating OS superiority over durvalumab plus chemotherapy rather than chemotherapy alone sets a substantially higher efficacy bar for ivonescimab.
First Known Phase 3 BTC Trial to Beat a PD-(L)1 Regimen on OS
According to Akeso, HARMONi-GI1 is the first known Phase 3 trial in advanced biliary tract cancer to demonstrate overall survival superiority over an anti-PD-(L)1 therapy plus chemotherapy.
That distinction could be clinically important.
Immunotherapy has already reshaped first-line BTC treatment. In addition to durvalumab, pembrolizumab plus gemcitabine/cisplatin demonstrated an OS benefit in the Phase 3 KEYNOTE-966 trial and received FDA approval in 2023.
However, both pivotal programs established the benefit of adding checkpoint inhibition to chemotherapy. HARMONi-GI1 goes one step further by asking whether a next-generation immunotherapy approach can outperform an existing checkpoint inhibitor regimen.
The positive OS result suggests that ivonescimab’s dual targeting of PD-1 and VEGF may offer additional benefit beyond conventional PD-(L)1 blockade.
Ivonescimab’s PD-1/VEGF Strategy
Ivonescimab is a tetravalent bispecific antibody designed by Akeso to simultaneously target PD-1 and vascular endothelial growth factor (VEGF).
The approach combines two well-established anticancer mechanisms in a single molecule.
PD-1 blockade is designed to restore antitumor immune activity, while VEGF inhibition targets tumor angiogenesis. VEGF signaling can also contribute to an immunosuppressive tumor microenvironment, providing a biological rationale for simultaneously targeting both pathways.
Akeso designed ivonescimab so that its PD-1 and VEGF binding functions may work cooperatively within the tumor microenvironment.
HARMONi-GI1 now provides Phase 3 evidence that this strategy may translate into improved survival beyond standard PD-L1 blockade in biliary tract cancer.
First Phase 3 Ivonescimab Success Outside Lung Cancer
The result also represents an important expansion of the ivonescimab story beyond non-small cell lung cancer (NSCLC).
Ivonescimab has already produced a series of positive late-stage results in lung cancer and is approved in China for multiple NSCLC indications.
According to Summit Therapeutics, HARMONi-GI1 represents the first Phase 3 ivonescimab readout outside NSCLC to demonstrate a significant overall survival benefit.
Ivonescimab is now being evaluated across an increasingly broad range of cancers. Summit says 16 Phase 3 studies of the drug have been announced, initiated or completed, including global programs in NSCLC as well as expansion into colorectal and urothelial cancers.
That breadth raises the possibility that ivonescimab could ultimately develop into a multi-tumor oncology franchise rather than remaining primarily a lung cancer drug.
An Important Validation — With Details Still Missing
Despite the strong topline announcement, several important questions remain unanswered.
Akeso has not yet disclosed the OS hazard ratio, median OS, PFS hazard ratio, response rates, duration of response or detailed safety findings from HARMONi-GI1.
Those numbers will be critical for determining the magnitude of ivonescimab’s advantage.
A statistically significant result does not by itself establish how large the clinical benefit is, and the eventual safety comparison will also be important given that ivonescimab simultaneously targets PD-1 and VEGF.
Another consideration is geography. HARMONi-GI1 is a single-region Phase 3 study conducted in China, sponsored by Akeso. Whether the results can be fully generalized to broader international BTC populations will therefore require further evaluation.
Still, the use of an active immunotherapy comparator makes the trial unusually informative. Instead of asking whether ivonescimab is better than chemotherapy, HARMONi-GI1 directly tested whether it could outperform a regimen already validated by a global Phase 3 trial and incorporated into clinical practice.
A Potential New Benchmark for Biliary Tract Cancer
Advanced biliary tract cancers—including intrahepatic and extrahepatic cholangiocarcinoma and gallbladder cancer—remain difficult malignancies with relatively poor long-term outcomes.
The introduction of checkpoint inhibitors such as durvalumab and pembrolizumab represented an important advance, but survival improvements have remained relatively modest.
HARMONi-GI1 therefore potentially represents the next step in the evolution of first-line treatment: moving from chemotherapy alone, to PD-(L)1 blockade plus chemotherapy, and potentially to dual PD-1/VEGF targeting plus chemotherapy.
If the full HARMONi-GI1 dataset confirms a substantial OS advantage with an acceptable safety profile, ivonescimab could emerge as a serious challenger to the current immunotherapy standard in advanced BTC.
More broadly, the result strengthens the case that PD-1/VEGF bispecific antibodies may represent an important next generation of cancer immunotherapy.
For Akeso, it is another major validation of ivonescimab. For the field, however, the most important numbers are still to come.
References
- Akeso Inc. “Ivonescimab Plus Chemotherapy Demonstrates Significant Overall Survival Benefit Versus Durvalumab Plus Chemotherapy in First-Line Biliary Tract Cancer: HARMONi-GI1 Meets Primary Endpoint.” August 26, 2026.
https://akesobio.com/en/media/akeso-news/260826/ - Akeso Inc. / PR Newswire. “Ivonescimab Plus Chemotherapy Demonstrates Significant Overall Survival Benefit Versus Durvalumab Plus Chemotherapy in First-Line Biliary Tract Cancer: HARMONi-GI1 Meets Primary Endpoint.” August 25, 2026.
https://www.prnewswire.com/news-releases/ivonescimab-plus-chemotherapy-demonstrates-significant-overall-survival-benefit-versus-durvalumab-plus-chemotherapy-in-first-line-biliary-tract-cancer-harmoni-gi1-meets-primary-endpoint-302859811.html - Summit Therapeutics. “Ivonescimab Plus Chemotherapy Demonstrates Statistically Significant Overall Survival Benefit Compared to Durvalumab Plus Chemotherapy in First-Line Advanced Biliary Tract Cancer in Single-Region Trial Conducted by Akeso in China.” August 26, 2026.
https://www.businesswire.com/news/home/20260825861058/en/Ivonescimab-Plus-Chemotherapy-Demonstrates-Statistically-Significant-Overall-Survival-Benefit-Compared-to-Durvalumab-Plus-Chemotherapy-in-First-Line-Advanced-Biliary-Tract-Cancer-in-Single-Region-Trial-Conducted-by-Akeso-in-China - Oh D-Y, He AR, Qin S, et al. “Durvalumab Plus Chemotherapy for Advanced Biliary Tract Cancer: A Post Hoc Analysis of the TOPAZ-1 Randomized Clinical Trial.” JAMA Oncology. Published July 9, 2026.
https://jamanetwork.com/journals/jamaoncology/fullarticle/2851484 - U.S. Food and Drug Administration / Clinical Cancer Research. “FDA Approval Summary: Durvalumab and Pembrolizumab, Immune Checkpoint Inhibitors for the Treatment of Biliary Tract Cancer.” Clinical Cancer Research. 2024;30(16):3371–3377.
https://aacrjournals.org/clincancerres/article/30/16/3371/746790/FDA-Approval-Summary-Durvalumab-and-Pembrolizumab
