FDA Fast Tracks Anti-HER2 Biparatopic ADC for Platinum-Resistant Ovarian Cancer

The FDA has granted fast track designation to JSKN003, a biparatopic HER2-targeting antibody-drug conjugate (ADC), for the treatment of platinum-resistant ovarian cancer (PROC), regardless of human epidermal growth factor 2 (HER2) expression.¹

The FDA fast track program aims to facilitate development and expedite the regulatory process of therapies that intend to treat serious conditions and fill unmet medical needs.² PROC is characterized by a dearth of effective treatment options and poor prognosis, underscoring a critical unmet need for patients. By binding to 2 HER2 epitopes on tumor cells and releasing topoisomerase I inhibitors via cellular endocytosis, JSKN003’s mechanism of action delivers selective antitumor activity while reducing hematological toxicity, potentially filling this gap.^1,3,4

With the designation, Alphamab Oncology, the sponsor, will now be able to interact more frequently with the FDA to receive guidance on drug development and clinical trial design, as well as be eligible for accelerated approval, priority review, and rolling review of a new drug application (NDA) if criteria are met.

Previously, the FDA awarded the agent orphan drug designation for treatment of gastric cancer and gastroesophageal junction cancer.¹ China’s National Medical Products Administration also granted breakthrough therapy designation to the agent for platinum-resistant recurrent epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.

What data support the designation?

JSKN003’s fast track designation is supported by positive clinical data from 2 early studies evaluating the agent’s safety and preliminary efficacy as monotherapy in advanced unresectable or metastatic solid tumors: the first-in-human phase 1 JSKN003-101 trial in Australia (NCT05494918) and the phase 1/2 JSKN003-102 trial in China (NCT05744427).^5,6

Specific to ovarian cancer, a pooled analysis of data from these trials, presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, showed an overall response rate (ORR) of 63% and median progression-free survival (PFS) of 7.7 months among 46 patients with PROC with varying HER2 expression levels.¹

Most recently, updated results of 26 patients with PROC from JSKN003-102 were presented in a poster at the 2025 European Society for Medical Oncology (ESMO). As of June 13, 2025, the ORR of 25 efficacy-evaluable patients was 32%, median PFS 4.1 months, and 9-month overall survival rate 65.4%, with efficacy observed across different HER2 expression subgroups.⁷

In the safety-evaluable population (n = 26), 92.3% (n = 24) of patients experienced treatment-related adverse events (TRAEs), with 15.4% (n = 4) experiencing grade 3 or 4 TRAEs. Some of the most frequently reported TRAEs included anemia (53.8%), nausea (42.3%), hypoalbuminemia (34.6%), decreased lymphocyte count (30.8%), increased aspartate aminotransferase (26.9%), and vomiting (26.9%).

Regarding next steps, a randomized phase 3 trial of JSKN003 has begun enrollment in China; in addition, a phase 2 study has been cleared to initiate in the United States.¹ The sponsor has also revealed plans for NDA submission in 2026.⁴

REFERENCES:

1. Alphamab Oncology Announces Biparatopic HER2-targeting ADC JSKN003 Was Granted Fast Track Designation by FDA for the Treatment of PROC. News release. PR Newswire. October 27, 2025. Accessed October 28, 2025. https://tinyurl.com/yc8ape4c

2. Fast Track. US Food & Drug Administration. Updated August 13, 2024. Accessed October 28, 2025. https://tinyurl.com/ms2695jn

3. Wang P, Guo K, Peng J, Sun J, Xu T. JSKN003, A Novel Biparatopic Anti-HER2 Antibody-Drug Conjugate, Exhibits Potent Antitumor Efficacy. Antib Ther. 2023;6(Supplement_1). doi.org/10.1093/abt/tbad014.009

4. JSKN003. Alphamab Oncology. Accessed October 28, 2025. https://tinyurl.com/47mzjxfr

5. First-In-Human Study in Subjects With Advanced or Metastatic Solid Malignant Tumors. ClinicalTrials.gov. Updated August 22, 2025. Accessed October 28, 2025. https://www.clinicaltrials.gov/study/NCT05494918

6. Safety and Tolerability of JSKN003 in Chinese Subjects With Advanced Solid Tumors. ClinicalTrials.gov. Updated September 15, 2025. Accessed October 28, 2025. https://www.clinicaltrials.gov/study/NCT05744427

7. Wu, X. Biparatopic anti-HER2 antibody drug conjugate (ADC) JSKN003 in the treatment of primary platinum-refractory ovarian cancer (OC). Poster presented at: ESMO 2025 Congress; October 17–21, 2025; Berlin, Germany.