Ivonescimab Combination Improves Survival in Advanced Biliary Tract Cancer

Treatment with ivonescimab plus chemotherapy improved overall survival compared with Imfinzi (durvalumab) plus chemotherapy for patients with previously untreated advanced biliary tract cancer in the phase 3 HARMONi-GI1 trial.

The trial met its main goal of improving overall survival, meaning patients who received the ivonescimab combination lived longer than those who received the Imfinzi combination. Ivonescimab plus chemotherapy also improved the amount of time patients lived without their cancer worsening and increased the percentage of patients whose tumors shrank or disappeared in response to treatment.

The findings are notable because researchers compared ivonescimab directly with Imfinzi plus gemcitabine and cisplatin, an established first-line treatment for advanced biliary tract cancer. The comparison tested whether ivonescimab could improve upon a treatment approach already used for patients with the disease.

Specific results, including how much longer patients lived and what side effects they experienced, have not yet been reported. The additional data will help show how meaningful the potential benefit may be for patients.

Why is the Imfinzi comparison important in HARMONi-GI1?

Imfinzi plus gemcitabine and cisplatin has been used as a first-line treatment for advanced biliary tract cancer since the Food and Drug Administration (FDA) approved the combination in 2022 based on findings from the phase 3 TOPAZ-1 trial.

HARMONi-GI1 tested whether a new immunotherapy approach could improve outcomes beyond those achieved with an established immunotherapy and chemotherapy combination.

According to the topline findings, patients who received ivonescimab plus chemotherapy lived longer than those who received the Imfinzi combination.

The direct comparison is important because ivonescimab demonstrated a survival benefit against a treatment already used in the first-line setting. If the complete findings show a meaningful survival improvement with manageable side effects, ivonescimab could potentially offer another first-line treatment option for patients with advanced biliary tract cancer.

How was the HARMONi-GI1 biliary tract cancer trial conducted?

The phase 3 HARMONi-GI1 trial included patients with locally advanced or metastatic biliary tract cancer who had not previously received systemic treatment for advanced disease.

Patients received either ivonescimab plus the chemotherapies gemcitabine and cisplatin or Imfinzi plus the same chemotherapy.

Researchers primarily evaluated how long patients lived. They also evaluated how long patients lived without their cancer worsening, how many patients responded to treatment and what side effects occurred.

How does ivonescimab work in biliary tract cancer?

Ivonescimab is an investigational bispecific antibody designed to target two pathways involved in cancer, PD-1 and VEGF.

PD-1 is part of a pathway that cancer cells can use to avoid being attacked by the immune system. VEGF helps tumors develop blood vessels that can support their growth.

By targeting both pathways at the same time, ivonescimab is designed to help the immune system recognize and attack cancer while interfering with the development of blood vessels that can support tumor growth.

The approach differs from Imfinzi, which targets PD-L1. Ivonescimab targets two different processes that can help cancer grow, helping the immune system recognize cancer while limiting the development of blood vessels that support tumor growth.

Ivonescimab has also been studied in lung cancer. The HARMONi-GI1 findings suggest that targeting PD-1 and VEGF together may also have potential in biliary tract cancer. Complete results are needed to determine how much benefit the approach provided and how its side effects compare with the Imfinzi combination.

What should patients know about the HARMONi-GI1 results?

Patients and their care teams do not yet know how much longer patients receiving ivonescimab lived compared with those receiving Imfinzi. Complete safety findings have also not been released, so it is not yet clear how side effects differed between the treatments.

HARMONi-GI1 was also conducted in China. Additional research may be needed to determine whether similar results are seen among patients in other parts of the world.

Ivonescimab remains investigational in the United States and is not currently FDA approved for biliary tract cancer.

Detailed findings from HARMONi-GI1 are expected to be presented at a future medical meeting and published in a peer-reviewed journal.

References

1. "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." News release. Summit Therapeutics, Aug. 25, 2026.
2. "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., Aug. 25, 2026.
3. "A Randomized, Controlled, Multi-Center Phase III Study of AK112 Combined With Gemcitabine Plus Cisplatin Versus Durvalumab Combined With Gemcitabine Plus Cisplatin as the First-Line Treatment for Patients With Advanced Biliary Tract Cancer." ClinicalTrials.gov. Updated Jan. 21, 2026.
4. Oh DY, et al. "Durvalumab or Placebo Plus Gemcitabine and Cisplatin in Participants With Advanced Biliary Tract Cancer (TOPAZ-1): Updated Overall Survival From a Randomised Phase 3 Study." The Lancet Gastroenterology & Hepatology. Published May 29, 2024.
5. "FDA Approves Durvalumab for Locally Advanced or Metastatic Biliary Tract Cancer." U.S. Food and Drug Administration. Published Sept. 2, 2022.

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