Akeso’s Biliary Tract Win Shows ivonescimab Beyond Lung Cancer

Akeso’s phase-3 win in biliary tract cancer confirms ivonescimab’s efficacy beyond lung cancer, CEO Michelle Xia, Ph.D., said on Tuesday.

Biliary tract cancer breakthrough

In a China phase-3 trial, ivonescimab plus chemotherapy extended patients’ lives compared with the standard combination of AstraZeneca’s Imfinzi and chemo for first-line treatment of advanced biliary tract cancer. Akeso called the overall survival (OS) win on the Harmoni-GI1 trial’s primary endpoint “clinically meaningful and statistically significant.” The study also met key secondary endpoints of progression-free survival and objective response rate, the company said.

The positive readout marks ivonescimab’s first successful late-stage trial outside lung cancer, validating the drug’s bispecific construct and underscoring its broad potential across tumor types, Xia told Fierce Biotech. She added that the bispecific design, which blocks both PD-1 and VEGF, differentiates ivonescimab from a simple drug combination.

Data and market context

Citi analysts noted that Harmoni-GI1’s outcome “further broadens the scope of evidence supporting ivonescimab’s unprecedented track record.” A Jefferies analyst called the win “unexpected” because biliary tract cancer is difficult to treat. Xia said she had always felt confident about the readout because phase-2 data were already encouraging.

In phase-2, 22 patients linked ivonescimab and chemo to a median OS of 16.8 months. In 2022, the FDA approved Imfinzi-chemo as the first immunotherapy-based treatment for biliary tract cancer after the regimen extended median OS to 12.9 months versus 11.3 months for chemo alone in the phase-3 Topaz-1 trial. Roche’s attempt to add bevacizumab to Tecentriq and chemo yielded no OS benefit.

Akeso finished enrolling Harmoni-GI1’s nearly 700 participants in just 11 months, as biliary tract cancer tracks at 100,000 new incidents annually in China alone and is growing. From a global perspective, the indication’s market is valued at between $1 billion to $4 billion, indicating room for expansion.

Addressing NSCLC concerns

Despite the biliary tract success, investors remain focused on the upcoming Harmoni-3 readout in first-line NSCLC, expected this year. The study had missed statistical significance on progression-free survival during a recently added interim analysis for the squamous cohort. When Chinese authorities approved ivonescimab plus chemo for first-line squamous NSCLC, the label revealed an updated PFS analysis of the China-only Harmoni-6 trial, showing the PFS advantage deteriorated from 40% during a February 2025 cut-off to 28% during a September 2025 cut-off.

Analysts suggested that the OS outcome from Harmoni-6 will also degrade with longer follow-up, and that the global Harmoni-3 OS improvement will fall below 20%. Based on a February 2026 cut-off, the China-only Harmoni-6 study reflected an OS improvement of 34%.

Xia argued that meeting OS, the gold standard in oncology, is sufficient to support ivonescimab plus chemo as a new standard of care, regardless of PFS changes. She cited the Keynote-407 trial, where Keytruda plus chemo’s PFS benefit declined slightly from 44% to 43% and OS benefit from 36% to 29% between initial and final analyses, yet Keytruda remained a standard.

Future trials and partnership prospects

Akeso’s U.S. partner, Summit Therapeutics, is not the sponsor of a new phase-2/3 trial registered by the ECOG-ACRIN Cancer Research Group, but the study is designed to be registrational. Summit is also exploring partnerships, having signed with Revolution Medicines for a combination with the RAS(ON) inhibitor daraxonrasib, which recently received FDA approval in pancreatic cancer.

The Harmoni-3 case raises questions about Summit’s ability to manage a large asset like ivonescimab, the first-in-class PD-1xVEGF bispecific, amid growing interest from Big Pharma. Xia said Summit “does need more resources and more investments.”

Industry watchers await the Harmoni-3 readout as the PD-1xVEGF space heats up quickly, with the drug’s broad-spectrum potential highlighted by ongoing trials in pancreatic cancer (Harmoni-GI2) and triple-negative breast cancer (Harmoni-BC1).