Ivonescimab Breakthrough Designation Highlights Progress in BTC Treatment

Hong Kong-based Akeso’s fifth breakthrough therapy designation (BTD) for ivonescimab, a bispecific antibody (bsAB), advances that therapeutic’s regulatory review in China. The BTD was granted by the Center for Drug Evaluation of China’s National Medical Products Administration (NMPA). Akeso, a biopharmaceutical company, reported that the designation applies to ivonescimab in combination with chemotherapy for the first-line treatment of advanced biliary tract cancer (BTC), a malignancy associated with limited therapeutic options and poor outcomes (1).

Ivonescimab targets programmed cell death protein 1 (PD-1) and vascular endothelial growth factor (VEGF). This latest designation follows four prior BTDs granted by the NMPA for ivonescimab across lung cancer indications and triple-negative breast cancer, reinforcing the breadth of the bsAb’s clinical development program. According to a company press release, ivonescimab is positioned as a first-in-class bsAb designed to concurrently modulate immune checkpoint signaling and tumor angiogenesis, two pathways implicated in tumor progression and resistance (1,2).

Why does breakthrough therapy designation matter for advanced BTC?

The NMPA’s BTD is intended to expedite the development and regulatory review of therapies that demonstrate substantial improvement over existing treatments for serious or life-threatening diseases. In advanced BTC, first-line treatment options have historically produced modest response rates and limited durability, underscoring the need for novel combination strategies (3).

The designation supports an ongoing registrational Phase III study, AK112-309 (HARMONi-GI1), a randomized, controlled, multicenter trial evaluating ivonescimab plus chemotherapy versus the PD-L1 inhibitor, durvalumab, in combination with chemotherapy for first-line treatment of advanced BTC. Patient enrollment in the study has been completed, according to the company, and the BTD is expected to facilitate closer regulatory interaction and potentially accelerate review timelines in China if the trial meets its predefined endpoints.

What clinical evidence supports ivonescimab in first-line BTC?

Clinical rationale for the Phase III program is supported by results from a Phase Ib/II study, which were presented at the 2024 American Society of Clinical Oncology Annual Meeting. In that study, ivonescimab combined with chemotherapy demonstrated an objective response rate of 63.6% and a disease control rate of 100% in patients with advanced BTC. Median progression-free survival was reported at 8.5 months, with a median overall survival of 16.8 months (1).

While cross-trial comparisons are inherently limited, these findings compare favorably with historical outcomes observed in advanced BTC and suggest that dual targeting of PD-1 and VEGF pathways may enhance antitumor activity in this setting. The results provided the basis for advancing the combination into a registrational Phase III trial.

How does ivonescimab fit within Akeso’s broader oncology strategy?

Ivonescimab is a central asset in Akeso’s oncology pipeline and signifies the company’s focus on bsAb development. The company’s R&D strategy is built around proprietary platforms, including its Tetrabody bsAb technology, antibody–drug conjugates, nucleic acid–based modalities, and cell therapies.

The company has advanced more than 50 assets across oncology, autoimmune disease, inflammation, and metabolic disorders. It has, to date, entered 26 candidates into clinical development, including multiple bispecific and multispecific antibodies. Seven of the company’s products have reached commercialization.

The fifth BTD for ivonescimab further expands its clinical footprint and highlights ongoing regulatory momentum as the company advances late-stage oncology programs targeting areas of high unmet medical need (1).

References

1. Akeso. Akeso Receives Fifth Breakthrough Therapy Designation from NMPA for Ivonescimab in First-Line Treatment of Advanced Biliary Tract Cancer. Press Release. Feb. 5, 2026.
2. Wang, Q.; Gao, J.; Di, W.; Wu, X. Anti-Angiogenesis Therapy Overcomes the Innate Resistance to PD-1/PD-L1 Blockade in VEGFA-overexpressed Mouse Tumor Models. Cancer Immunol., Immunother. 2020, 69 (9), 1781–1799. DOI: 10.1007/s00262-020-02576-x 
3. Rimassaa, L.; Lamarcac, A.; O'Kane, G. M.; et al. New Systemic Treatment Paradigms in Advanced Biliary Tract Cancer and Variations in Patient Access Across Europe. The Lancet Regional Health—Europe 2025, 50, 101170.