JSKN003 Nets FDA Breakthrough Therapy Designation in Pretreated HER2+ Platinum-Resistant Ovarian Cancer

JSKN003, a biparatopic HER2-targeted antibody-drug conjugate, has received breakthrough therapy designation from the FDA for the treatment of adult patients with advanced or metastatic, platinum-resistant, recurrent epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancers with a HER2 expression of 1+, 2+, and 3+ by immunohistochemistry who have received prior treatment with bevacizumab (Avastin).¹

Findings from a pooled analysis of the phase 1 JSKN003-101 (NCT05494918) and phase 1/2 JSKN003-102 (NCT05744427) clinical trials supported the regulatory decision. Data from the pooled analysis presented during the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting demonstrated that patients with platinum-resistant ovarian cancer who received JSKN003 (n = 46) achieved an overall response rate (ORR) of 63.0% (95% CI, 47.5%-76.8%), with a complete response (CR) rate of 4.3% and a disease control rate (DCR) of 93.5% (95% CI, 82.1%-98.6%).² At the February 28, 2025, data cutoff at a median follow-up of 9.3 months, the median progression-free survival (PFS) was 7.7 months (95% CI, 5.7-9.7), and the 9-month overall survival (OS) rate was 89.9% (95% CI, 75.0%-96.1%).

JSKN003 has previously received orphan drug designation from the FDA for the treatment of patients with gastric and gastroesophageal cancers.¹ The agent has also received fast track designation from the FDA for the treatment of patients with advanced or metastatic platinum-resistant recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancers not restricted by HER2 expression.

What was the design of the pooled analysis?

JSKN003-101 was conducted in Australia, and JSKN003-102 was conducted in China.² Both studies enrolled patients with advanced solid tumors, and tissue samples were collected for central lab assessment of HER2 expression status.

Patients received JSKN003 at doses of 4.2 mg/kg (n = 2), 5.2 mg/kg (n = 2), 6.3 mg/kg (n = 40), 7.3 mg/kg (n = 1), and 8.4 mg/kg (n = 1) every 3 weeks. The recommended phase 2 dose of JSKN003 was established at 6.3 mg/kg.

What were the additional efficacy and safety data?

Further efficacy data from the pooled analysis demonstrated that patients with a HER2 expression per immunohistochemistry of 1+/2+/3+ (n = 18) achieved an ORR of 72.2% (95% CI, 46.5%-90.3%), a DCR of 94.4% (95% CI, 72.7%-99.9%), and a CR rate of 11.1%. The median PFS was 9.4 months (95% CI, 5.7-not estimable), and the 9-month OS rate was 82.5% (95% CI, 54.9%-94.0%).

In terms of safety, most patients in the overall population (95.7%) experienced any-grade treatment-related adverse effects (TRAEs). Grade 3 to 4 TRAEs (19.6%) and serious TRAEs (13.0%) also occurred. No TRAEs leading to death were reported. The most common any-grade TRAEs that occurred in more than 15% of patients included anemia (39.1%), increased aspartate aminotransferase levels (39.1%), diarrhea (37.0%), and nausea (37.0%).

The authors of the pooled analysis noted that a confirmatory phase 3 trial (NCT06751485) is currently enrolling patients, regardless of HER2 expression, to validate JSKN003 as a treatment option in this patient population.

References

1. Alphamab Oncology announces biparatopic HER2-targeting ADC JSKN003 was granted breakthrough therapy designation by the FDA for the treatment of PROC. News release. Alphamab Oncology. December 20, 2025. Accessed December 22, 2025. https://www.alphamabonc.com/en/html/news/2744.html
2. Wu X, Chen Y, Rao Q, et al. JSKN003, a biparatopic anti-HER2 antibody drug conjugate (ADC), in the treatment of platinum-resistant ovarian cancer (PROC): updated findings from two clinical trials. J Clin Oncol. 2025;43(suppl 16):5557. doi:10.1200/JCO.2025.43.16_suppl.5557