Ivonescimab (Idafang®; Akeso Biopharma; previously known as AK112) has received Breakthrough Therapy Designation (BTD) in China for the treatment of triple-negative breast cancer (TNBC).* [1] Ivonescimab is a potential first-in-class, humanized, tetravalent bispecific monoclonal antibody targeting programmed cell death protein 1 (PD-1) and vascular endothelial growth factor (VEGF)-A, currently in a Phase 3 trial. This investigational agent is poised to become the first potential next-generation bispecific immuno-oncology (IO) agent as a first-line treatment for TNBC in China.[2]
Ivonescimab targets both PD-1 and VEGF-A, thereby activating the immune system and blocking angiogenesis. In a Phase 2 trial combining ivonescimab with chemotherapy, the treatment demonstrated an objective response rate of approximately 78.8% and a 100% disease control rate, with a median progression-free survival of 9.3 months and manageable adverse events. The Phase 3 HARMONi BC1/AK112 trial (NCT06767527) for TNBC is expected to be completed by December 2026.
Treatment landscape
According to GlobalData’s Pharmaceutical Intelligence Center, the current TNBC treatment landscape in China includes checkpoint inhibitors such as pembrolizumab (Keytruda®; Merck & Co) and toripalimab (Tuoyi®; Shanghai Junshi Biosciences) as first-line therapies, along with antibody-drug conjugates (ADCs) like sacituzumab govitecan (Trodelvy®; Gillead) and the investigational sacituzumab tirumotecan (Giatelai®; Merck & Co/MSD and Kelun-Biotech), for second and later lines of therapy. Additionally, Pumitamig (also known as BNT327 and BMS986545), an investigational bispecific antibody being developed by BioNTech and Bristol Myers Squibb (BMS) for cancer treatment, is also competing in this area.
China now leads TNBC IO innovation, ahead of the US, with two marketed I-O therapies with pembrolizumab and toripalimab, and two drugs, ivonescimab and Pumitamig, in Phase 3 for TNBC. In the United States, the Food and Drug Administration (FDA) approved two IO therapies, pembrolizumab and pembrolizumab + berahyaluronidase alfa; Keytruda QLEX™; Merck & Co/MSD), while eftilagimod alfa (IMP321), a recombinant soluble LAG-3 (fusion) protein, being developed by Immutep, and Pumitamig are in Phase 3 trials for TNBC.
“TNBC is one of the most aggressive breast cancer subtypes, typically associated with poor prognosis and limited targeted therapy options. A positive outcome in the Phase III trial for ivonescimab as a first-line treatment could significantly improve clinical outcomes for patients,” said Chilamula Srija, Pharma Analyst at GlobalData.
Ivonescimab has previously received three Breakthrough Therapy Designations (BTD) for non-small cell lung cancer (NSCLC). In May 2024, Akeso obtained its first National Medical Products Administration (NMPA-) approval for ivonescimab for EGFR TKI-resistant NSCLC, followed by approval for first-line PD-L1-positive advanced NSCLC. It has also shown positive Phase 3 overall survival data and head-to-head results compared to pembrolizumab.
“Despite advances in oncology, TNBC remains a significant clinical challenge due to difficulty in targeting it, as it lacks expression of estrogen receptors, progesterone receptors, and HER2. This underscores the need for novel options, such as ivonescimab. Additionally, the advantages of prior NSCLC approval and National Reimbursement Drug List listing present an opportunity for Akeso to compete with existing therapies and late-stage pipeline drugs in penetrating the TNBC market in China,” Srija concluded.
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Note: * Ivonescimab is also investigated for the treatment of non-small cell lung cancer (NSCLC) and other solid tumours, including breast cancer, liver cancer, and gastric cancer.[1]
Clinical trials
AK112 or Placebo Plus Nab-Paclitaxel as First-line Treatment in Inoperable Locally Advanced/ Metastatic Triple-negative Breast Cancer ClinicalTrials.gov ID NCT06767527 AK112 in Combination With Chemotherapy in Advanced Squamous Non-Small Cell Lung Cancer – ClinicalTrials.gov ID NCT05840016
Reference
[1] Dhillon S. Ivonescimab: First Approval. Drugs. 2024 Sep;84(9):1135-1142. doi: 10.1007/s40265-024-02073-w. Epub 2024 Jul 29. PMID: 39073550.
[2] Zhang C, Bi J, Huang Y, Ke Z, Yuan Z, Ruan H, Pi G, Li Y, Shao J, Han G. Neoadjuvant stereotactic body radiotherapy combined with chemotherapy and Ivonescimab for Chinese luminal-type breast cancer patients: study protocol for a single-arm, open-label, phase II trial. BMJ Open. 2025 Sep 10;15(9):e102952. doi: 10.1136/bmjopen-2025-102952. PMID: 40935417; PMCID: PMC12519357.
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