JSKN003 Receives FDA Fast Track Designation in Advanced PROC

The FDA has granted fast track designation to biparatopic HER2-targeting antibody drug conjugate (ADC) JSKN003 for the treatment of patients with advanced or metastatic platinum-resistant epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer (PROC), according to a news release from the drug’s developer, Alphamab Oncology.¹

The regulatory decision is supported by data from a pooled analysis of the phase 1 JSKN003-101 trial (NCT05494918) in Australia and the phase 1/2 JSKN003-102 trial (NCT05744427) conducted in China presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.² Both trials assessed patients with solid tumors who received the investigational agent as monotherapy across multiple dose levels from 4.2 to 8.4 mg/kg.

Results from the pooled analysis revealed that among patients with PROC treated with JSKN003 (n = 46), the objective response rate (ORR) was 63.0% (95% CI, 47.5%-76.8%), with 2 complete responses (4.3%) and 27 partial responses (58.7%) after a median follow-up of 9.3 months. The disease control rate (DCR) was 93.5% (95% CI, 82.1%-98.6%). Additionally, this patient population experienced a median progression-free survival (PFS) of 7.7 months (95% CI, 5.7-9.7), with a 9-month overall survival (OS) rate of 89.9% (95% CI, 75.0%-96.1%).

Furthermore, patients with confirmed HER2 immunohistochemistry (IHC; n = 18) experienced enhanced responses, with an ORR of 72.2% (95% CI, 46.5%-90.3%) and a DCR of 94.4% (95% CI, 72.7%-99.9%), with both complete responses occurring in this patient subgroup. The median PFS was 9.4 months (95% CI, 5.7-not evaluable [NE]), and the 9-month OS rate was 82.5% (95% CI, 54.9%-94.0%).

“With extended follow-up, JSKN003 demonstrated robust PFS improvement in PROC, along with early signals of OS benefit,” study investigator Xiaohua Wu, MD, PhD, of the Department of Gynecologic Oncology at Fudan University Shanghai Cancer Center in Shanghai, China, wrote in the presentation with coinvestigators.² “A confirmatory trial (NCT06751485) is currently enrolling all comers regardless of HER2 expression to validate JSKN003 as a treatment option for this patient population.”

Patients in the pooled analysis with PROC (n = 48) had tissue samples collected for central lab assessment of HER2 expression status. Most patients received the recommended phase 2 dose of 6.3 mg/kg (n = 40), with 2 patients receiving 4.2 or 5.2 mg/kg each, and 1 patient receiving 7.3 or 8.4 mg/kg each. Treatment was given once every 3 weeks.

Among all patients included in the efficacy analysis (n = 46), the median age was 59.0 years (IQR, 53.0-63.0). A total of 84.8% of patients were Asian, 56.5% had an ECOG performance status of 1, and 91.3% had a tumor diagnosis of ovarian cancer. Most patients had an IHC of 0 (45.7%) or 1 (21.7%), a platinum-free interval of greater than 3 months (50.0%), and had received 3 or more lines of prior anti-cancer therapy (65.2%), including bevacizumab (Avastin; 80.4%) and PARP inhibition (63.0%).

In both trials, primary end points included maximum tolerated dose and adverse effects (AEs)/dose-limiting toxicities.^3,4 An additional primary end point in the phase 1/2 trial was ORR. Secondary end points in both trials included PFS and duration of response.

A total of 95.7% of patients in the pooled analysis experienced treatment-related AEs (TRAEs). Grade 3/4 TRAEs were reported in 19.6% of patients, with 13.0% experiencing serious TRAEs. No TRAEs resulted in death.

The most common TRAEs of any grade included anemia (39.1%), aspartate aminotransferase increases (39.1%), diarrhea (37.0%), nausea (37.0%), and asthenia (34.8%). The most common grade 3/4 TRAEs included anemia (6.5%), lymphocyte count decreases (4.3%), asthenia, and platelet count decreases (2.2% each). Of note, interstitial lung disease events were reported in 5 (10.9%) patients and were grade 1 or 2 in severity.

According to the developers, a phase 3 clinical trial evaluating JSKN003 in PROC is ongoing in China, and a phase 2 trial has been approved to begin enrollment in the US.

References

1. Alphamab Oncology announces biparatopic HER2-targeting ADC JSKN003 was granted fast track designation by FDA for the treatment of PROC. News release. Alphamab Oncology. October 27, 2025. Accessed October 28, 2025. https://tinyurl.com/5n87t26z
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):107. doi: 10.1200/JCO.2025.43.16_suppl.5557
3. First-in-human study in subjects with advanced or metastatic solid malignant tumors. ClinicalTrials.gov. Updated August 22, 2025. Accessed October 28, 2025. https://tinyurl.com/nzv8zszn
4. Safety and tolerability of JSKN003 in Chinese subjects with advanced solid tumors. Updated September 15, 2025. Accessed October 28, 2025. https://tinyurl.com/mvdur8sm