Akeso’s bispecific antibody improves survival in phase 3 biliary tract cancer trial, expanding beyond lung cancer

Akeso’s bispecific antibody drug ivonescimab improved survival in a phase 3 biliary tract cancer trial. It marks the first achievement demonstrating the potential to expand its indications beyond non-small cell lung cancer to other cancer types.

Akeso said on the 25th (local time) that the combination of ivonescimab and chemotherapy significantly extended patients’ overall survival (OS) compared with AstraZeneca’s Imfinzi plus chemotherapy standard combination in the first-line treatment of advanced biliary tract cancer.

The company said the improvement in overall survival, the primary endpoint of the phase 3 HARMONY-GI1 trial, was “clinically meaningful and statistically significant.” Key secondary endpoints, including progression-free survival (PFS) and objective response rate (ORR), were also met.

Michelle Xia, Akeso’s chief executive officer (CEO), said in an interview with Fierce Pharma that “these results represent ivonescimab’s first late-stage clinical success outside lung cancer” and “demonstrate the value of the bispecific antibody structure and support its potential across multiple cancer types.”

Detailed data were not disclosed. Akeso plans to present the full results at the European Society for Medical Oncology (ESMO) annual meeting in October.

In an earlier phase 2 trial involving 22 patients, the ivonescimab combination recorded a median overall survival of 16.8 months. The Imfinzi combination, approved by the US Food and Drug Administration (FDA) in 2022 as the first immunotherapy for biliary tract cancer, showed a median overall survival of 12.9 months in the phase 3 TOPAZ-1 trial.

CEO Xia emphasized that “HARMONY-GI1 once again demonstrated that ivonescimab’s mechanism of action differs from simply combining two drugs.” The company maintains that the bispecific antibody structure has broad potential across multiple cancer types because it simultaneously enhances PD-1 and VEGF inhibition.

Akeso is also conducting the HARMONY-GI2 trial in the first-line treatment of pancreatic cancer and the HARMONY-BC1 trial in the first-line treatment of triple-negative breast cancer.

Outside China, the US ECOG-ACRIN Cancer Research Group plans to begin a phase 2/3 trial early next year to evaluate the ivonescimab combination in biliary tract cancer among global patients. CEO Xia explained that although Akeso’s US partner Summit Therapeutics will not serve as the sponsor, the trial was designed for registration purposes.

Biliary tract cancer accounts for 100,000 new patients annually in China alone, and the number is increasing. Akeso completed enrollment of approximately 700 patients in HARMONY-GI1 in 11 months. Citing market research, CEO Xia estimated the global biliary tract cancer market at $1 billion-$4 billion (approximately 1.38 trillion-5.52 trillion won).

Meanwhile, controversy continues over ivonescimab’s non-small cell lung cancer data. After Chinese authorities approved the ivonescimab combination for the first-line treatment of squamous non-small cell lung cancer, the progression-free survival benefit reported in the publicly disclosed Chinese HARMONY-6 trial was found to have declined from 40% based on February 2025 data to 28% as of September of the same year.

Investors are watching the results of the global phase 3 HARMONY-3 trial, which are expected at the end of this year. Concerns have been raised that if the magnitude of the progression-free survival benefit declines, the FDA may have difficulty granting accelerated approval without mature overall survival data.

In response, CEO Xia countered that HARMONY-6 met both its progression-free survival and overall survival endpoints at the interim analysis, making those results the final analysis, and that subsequent follow-up was exploratory in nature and did not change the statistical significance status.

He explained that it is not uncommon for the magnitude of benefit from immunotherapy to decrease during long-term follow-up after the primary analysis. For example, in the phase 3 KEYNOTE-407 trial of the Keytruda combination, the progression-free survival benefit declined slightly from 44% initially to 43% at the final analysis, while the overall survival benefit decreased from 36% to 29%; however, Keytruda’s position was not shaken.

CEO Xia said, “Scientific questions ultimately require scientific evidence,” adding, “Scientific outcomes cannot be determined through simple linear extrapolation.”

Questions have also been raised about the capabilities of Summit Therapeutics, ivonescimab’s development partner outside China. Summit previously failed to meet the overall survival endpoint in the first global phase 3 HARMONY trial for patients with EGFR-mutated non-small cell lung cancer because of delays in enrolling patients outside China.

CEO Xia said, “I agree with the observation that Summit needs more resources and investment.”

Competition in the PD-1xVEGF bispecific antibody field is also intensifying. Merck registered the first global trial of its PD-1xVEGF candidate MK-2010 on the 25th, while AbbVie disclosed plans earlier this month for a global phase 3 trial of ABBV-1480, which it licensed from China’s Remegen, targeting the first-line treatment of squamous non-small cell lung cancer.