KN026 (anbenitamab) NDA Accepted by NMPA: First Domestic HER2 Bispecific in Gastric Cancer

On September 11, 2025, Alphamab Oncology and CSPC Pharmaceutical Group announced that China’s National Medical Products Administration (NMPA) has accepted the New Drug Application (NDA) for KN026 (anbenitamab), a novel anti-HER2 bispecific antibody. The application covers KN026 in combination with chemotherapy for the treatment of HER2-positive locally advanced, recurrent, or metastatic gastric/gastroesophageal junction (GEJ) adenocarcinoma in patients who have failed at least one prior systemic regimen, including trastuzumab plus chemotherapy. The NDA was submitted on September 7 and formally accepted on September 11. This makes KN026 the first domestically developed HER2 bispecific antibody to reach the NDA stage in China for gastric/GEJ cancer, addressing a critical gap in the second-line setting.

A Novel Mechanism of Action

KN026, discovered using Alphamab’s proprietary CRIB platform, binds to two non-overlapping epitopes of the HER2 receptor (domains II and IV). This biparatopic design enhances receptor clustering, internalization, and degradation, offering potential advantages over traditional HER2 monoclonal antibodies such as trastuzumab. Preclinical and early clinical studies suggest that KN026 may overcome resistance to prior HER2-directed therapies, with a manageable safety profile and low immunogenicity signals reported to date.

Pivotal Clinical Evidence

The NDA submission is supported by data from the pivotal KC-WISE study (NCT05427383), a Phase II/III trial evaluating KN026 plus chemotherapy in the second-line gastric/GEJ setting. In May 2025, Alphamab and CSPC announced that the trial met its primary endpoint of progression-free survival (PFS), with a trend toward overall survival (OS) benefit. Interim findings reported:

• Objective Response Rate (ORR): ~40%
• Median PFS: 8.6 months
• Median OS: 13.2 months

These results build on earlier Phase II data presented at the European Society for Medical Oncology (ESMO) 2023, which also showed meaningful antitumor activity. Safety analyses to date indicate a tolerable profile without significant cardiac toxicity.

Regulatory and Development Milestones

KN026’s clinical development has been supported by China’s regulatory framework:

• Breakthrough Therapy Designation granted by the Center for Drug Evaluation (CDE) in November 2023.
• Priority Review designation granted in August 2025, which shortens the NDA review timeline to approximately 130 working days, compared with the standard 200-day review. While regulatory timing depends on CDE queries, inspections, and drug testing, approval could realistically occur in 2026.

Strategic Partnership

Alphamab Oncology licensed KN026’s rights for gastric and breast cancer in mainland China to CSPC’s subsidiary JMT-Bio in August 2021 through a deal valued at RMB 1 billion. CSPC brings extensive development, manufacturing, and commercialization capabilities, accelerating KN026’s clinical progress. This collaboration has positioned KN026 at the forefront of China’s innovative oncology pipeline.

Competitive Landscape

KN026 is the first domestic HER2 bispecific antibody to reach NDA acceptance for gastric/GEJ cancer in China. The competitive context includes:

• Zanidatamab (BeiGene/Zymeworks) – a dual HER2 antibody, conditionally approved in China for biliary tract cancer (May 2025), but not for gastric cancer.
• TQB2930 (Chia Tai-Tianqing) – an investigational HER2 bispecific currently in Phase III for breast cancer.

Given that nearly half of global gastric cancer cases occur in China, KN026’s potential approval would mark a significant milestone for patients in an area of high unmet need.

Outlook

If approved, KN026 would represent a first-in-class HER2-targeted bispecific therapy for second-line gastric/GEJ adenocarcinoma in China. Alongside ongoing Phase III trials in breast cancer (with data expected in 2026), KN026 may establish itself as a cornerstone of HER2 therapy across multiple indications. With regulatory review underway under the Priority pathway, KN026 could emerge as a key differentiator in China’s oncology landscape.

References

1. Jiangsu Alphamab Biopharmaceuticals Co., Ltd. KN026 Granted Breakthrough Therapy Designation by CDE for HER2-Positive Gastric/GEJ Cancer. Jiangsu Alphamab Press Release, November 7, 2023.
2. CSPC Pharmaceutical Group Limited. Announcement: Exclusive License Agreement for KN026 with Jiangsu Alphamab. CSPC Press Release, August 24, 2021.
3. Xu, B.; Li, W.; Zhang, Q.; et al. Safety and Efficacy of KN026, an Anti-HER2 Bispecific Antibody, in Patients with HER2-Positive Solid Tumors. J. Clin. Oncol. 2023, 41 (16_suppl), 1047.
4. JMT-Bio Technology Co., Ltd. Strategic Partnership with Jiangsu Alphamab for KN026 Development and Commercialization. JMT-Bio Press Release, August 23, 2021.
5. China National Medical Products Administration. KN026 New Drug Application Accepted for HER2-Positive Gastric/GEJ Cancer. NMPA Notice, September 11, 2025.
6. Wang, J.; Zhang, Y.; Liu, Y.; et al. Interim Analysis of KC-WISE: A Phase II/III Study of KN026 Plus Chemotherapy in Second-Line HER2-Positive Gastric/GEJ Cancer. Ann. Oncol. 2025, 36 (Suppl. 2), S402–S403.
7. Jiangsu Alphamab Biopharmaceuticals Co., Ltd. KN026 Granted Priority Review for Second-Line Gastric Cancer Indication. Jiangsu Alphamab Press Release, August 28, 2025.
8. Zhang, L.; Chen, X.; Xu, B.; et al. KN026 Combined with Chemotherapy in HER2-Positive Gastric Cancer: Preliminary Results from Phase II Trials. Eur. J. Cancer 2023, 190 (Suppl. 1), 112950.
9. CSPC Pharmaceutical Group Limited. KN026 Phase II/III KC-WISE Trial Meets Primary Endpoint at Interim Analysis. CSPC Press Release, May 15, 2025.
10. BeiGene Co., Ltd. Zanidatamab Approved by NMPA for Biliary Tract Cancer. BeiGene Press Release, May 29, 2025.
11. Chia Tai-Tianqing Pharmaceutical Group. TQB2930 Phase III Trial Initiated for HER2-Positive Breast Cancer. CTTQ Press Release, June 2024.

Disclaimer: This article is for informational purposes only and does not constitute medical or investment advice. Readers should consult primary literature and official regulatory sources for verification.