Akeso Succeeds in Phase 3 Biliary Tract Cancer Trial, Begins Expanding Beyond Lung Cancer

China’s Akeso said its PD-1/VEGF bispecific antibody ivonescimab successfully extended survival significantly compared with standard therapy in the first-line treatment of advanced biliary tract cancer. This is the first time the drug has succeeded in a Phase 3 trial in an indication outside lung cancer.

Akeso said on the 26th local time that, in the Phase 3 HARMONY-GI1 trial conducted in China, the combination of ivonescimab and chemotherapy improved overall survival (OS) in patients receiving first-line treatment for advanced biliary tract cancer compared with AstraZeneca’s Imfinzi plus chemotherapy.

The company said the improvement in OS, the primary endpoint, was “clinically meaningful and statistically significant,” adding that key secondary endpoints, including progression-free survival (PFS) and objective response rate (ORR), were also met.

Michelle Sha, Akeso’s chief executive officer (CEO), said the results validate ivonescimab’s bispecific antibody structure and support its broad potential across various cancer types.

Although specific data were not disclosed, Citi analysts said in a report that day that the HARMONY-GI1 results “further expand the body of evidence supporting ivonescimab’s unprecedented track record.” Jefferies analysts described the success as “unexpected,” given that biliary tract cancer is difficult to treat.

In an earlier Phase 2 trial involving 22 patients, the median OS for ivonescimab plus chemotherapy was 16.8 months. In 2022, the U.S. Food and Drug Administration (FDA) approved Imfinzi plus chemotherapy as the first immunotherapy for biliary tract cancer after the combination extended median OS to 12.9 months in the Phase 3 TOPAZ-1 trial.

CEO Sha said, “HARMONY-GI1 once again demonstrated that ivonescimab’s mechanism of action differs from a simple combination of two drugs,” emphasizing that the bispecific antibody structure simultaneously enhances PD-1 and VEGF inhibition and “has the potential to produce efficacy across a broad range of cancer types.”

The company is also conducting the HARMONY-GI2 trial in first-line pancreatic cancer and the HARMONY-BC1 trial in first-line triple-negative breast cancer. CEO Sha declined to provide further details, saying that detailed results are scheduled to be presented at the European Society for Medical Oncology (ESMO) annual meeting in October.

Biliary tract cancer has substantial unmet medical needs. CEO Sha said that China alone has 100,000 new cases annually and that the number is increasing, allowing enrollment of approximately 700 patients in HARMONY-GI1 to be completed in 11 months. Citing market research, she added that the global biliary tract cancer market is valued at $1 billion to $4 billion (approximately 1.38 trillion won to 5.52 trillion won) and has room to grow.

Meanwhile, CEO Sha directly rebutted concerns about worsening non-small cell lung cancer (NSCLC) data. In the China-only HARMONY-6 trial, the magnitude of PFS improvement declined from 40% as of the February 2025 data cutoff to 28% as of September, increasing investor concerns about the results of the global Phase 3 HARMONY-3 trial.

CEO Sha explained that HARMONY-6 met both the PFS and OS endpoints at the interim analysis, making those results the final analysis, and that all follow-up observations thereafter were exploratory, so the statistical significance status had not changed. “Scientific questions ultimately require scientific proof,” she said, adding, “Scientific results cannot be determined through simple linear extrapolation.”

She also noted that it is not uncommon for the effect size of immunotherapy to decline during long-term follow-up after the primary analysis. In the Phase 3 KEYNOTE-407 trial of Keytruda plus chemotherapy, for example, the magnitude of PFS improvement declined slightly from 44% initially to 43% at the final analysis, while the magnitude of OS improvement declined from 36% to 29%; however, she said, Keytruda’s position remained unchanged.

Ivonescimab’s U.S. partner, Summit Therapeutics, added an interim PFS analysis for the squamous cell carcinoma cohort of HARMONY-3 earlier this year and began early discussions with regulators. CEO Sha said the China HARMONY-6 trial enrolled patients faster than the global HARMONY-3 trial, so Summit’s analysis was conducted somewhat earlier, but added, “The Akeso team is even more confident in HARMONY-3.”

Competition in the PD-1/VEGF bispecific antibody field is also intensifying. On the 25th, Merck disclosed the first global clinical trial of MK-2010, a PD-1/VEGF candidate licensed from China’s SBP Group, while AbbVie also disclosed the global Phase 3 trial of ABBV-1480, licensed from China’s Remegen earlier this month, targeting first-line squamous NSCLC.