Key Takeaways
- FDA Approval for JSKN003 Trial: Alphamab Oncology received FDA approval to start a Phase II trial for the novel therapy for platinum-resistant ovarian cancer, expanding treatment options regardless of HER2 expression levels.
- Promising Clinical Data: Early phase trials show a 63% objective response rate (ORR) and durable progression-free survival, with manageable safety profiles in patients with platinum-resistant ovarian cancer.
- Ongoing Global Development: Alphamab advances multiple Phase III trials in China and holds breakthrough therapy designation, reinforcing JSKN003’s potential in treating HER2-expressing solid tumors.
The FDA has granted Alphamab Oncology approval to initiate a Phase II clinical trial (JSKN003-202) of its anti-HER2 biparatopic antibody-drug conjugate (ADC) JSKN003 for treating platinum-resistant recurrent epithelial ovarian cancer, primary peritoneal cancer, and fallopian tube cancer, regardless of HER2 expression levels. According to the company, JSKN003 is designed to bind to HER2 on tumor cells and deliver topoisomerase I inhibitors intracellularly, exhibiting improved serum stability and a stronger bystander effect compared to existing ADCs, thereby broadening its therapeutic window.
What does FDA Clearance mean for Alphamab’s JSKN003 in Ovarian Cancer Treatment?
The randomized, open-label, multi-center JSKN003-202 trial aims to evaluate the safety and efficacy of JSKN003 in patients with platinum-resistant recurrent epithelial ovarian cancer, primary peritoneal, or fallopian tube cancer, and to determine the recommended Phase III dose.
Ongoing Phase III Trials and Regulatory Milestones
Alphamab is actively conducting three Phase III trials in China investigating JSKN003 for HER2-low breast cancer, platinum-resistant ovarian cancer (PROC), and HER2-positive breast cancer, with the company reporting all three trials are progressing smoothly. In March, the ADC earned breakthrough therapy status from the National Medical Products Administration of China’s Center for Drug Evaluation, specifically for treating PROC without limiting to HER2 expression.1
Earlier this week, the FDA also granted Orphan Drug Designation to JSKN003 for the treatment of gastric cancer and gastroesophageal junction cancer.2
Clinical Data Highlights from Early-Phase Trials
- In June, Alphamab presented multiple clinical data updates for JSKN003 at the 2025 American Society of Clinical Oncology Annual Meeting.
- Results from the Phase I JSKN003-101 trial (NCT05494918) in Australia and the Phase I/II JSKN003-102 trial (NCT05744427) in China provide important insights into the safety, tolerability, and potential efficacy of JSKN003 in patients with advanced solid tumors, including PROC.
- As of February 28, 2025, the trials included 46 patients with PROC, all receiving JSKN003 every three weeks across five dose levels.
- This included two patients receiving 5.2 mg/kg, 40 patients treated with the recommended Phase II dose of 6.3 mg/kg, and one patient each at doses of 7.3 mg/kg and 8.4 mg/kg.
- Results from a pooled analysis of the trials showed an objective response rate of 63%, with 91.3% of patients experiencing tumor shrinkage.
- The median progression-free survival was 7.7 months and the nine-month overall survival rate was 89.9%.
- Notably, efficacy was observed across all HER2 expression levels, including patients with no detectable HER2.
- Treatment-related adverse events (TEAEs) of grade 3 or higher occurred in about 20% of patients.
- All TEAEs were considered mild to moderate in severity, with interstitial lung disease reported in 11% of patients.3
Ovarian Cancer in the United States: Disease Burden and Trends
According to the American Cancer Society, ovarian cancer is one of the leading causes of cancer deaths among women in the United States. By the end of 2025, it is estimated that there will be 20,890 new cases and approximately 12,730 deaths from ovarian cancer in the United States.
The disease is more common in older women, with more than half of all cases diagnosed in women 63 years of age and older. It is reported to be more common in White women than Black women.
The number of women dying from ovarian cancer has declined, likely because of improved therapies and a reduction in new cases. Since 1976, ovarian cancer death rates have dropped by 43%, with the majority of this improvement occurring after the mid-2000s.4
Looking Ahead
Alphamab stated that the initiation of the Phase II trial will advance the clinical evaluation of JSKN003 across diverse patient populations. Ongoing studies are expected to further clarify its safety and efficacy in platinum-resistant ovarian cancer and related tumors.1
References
- Alphamab Oncology Announces Anti-HER2 Biparatopic ADC JSKN003 Received U.S. FDA IND Approval to Initiate a Phase II Clinical Study for Platinum-Resistant Ovarian Cancer. PR Newswire. July 31, 2025. Accessed August 1, 2025. https://prnmedia.prnewswire.com/news-releases/alphamab-oncology-announces-anti-her2-biparatopic-adc-jskn003-received-us-fda-ind-approval-to-initiate-a-phase-ii-clinical-study-for-platinum-resistant-ovarian-cancer-302518558.html
- Alphamab Oncology Announces Anti-HER2 Biparatopic ADC JSKN003 Obtained Orphan Drug Designation from the U.S. FDA for the Treatment of GC/GEJ. PR Newswire. July 29, 2025. Accessed August 1, 2025. https://prnmedia.prnewswire.com/news-releases/alphamab-oncology-announces-anti-her2-biparatopic-adc-jskn003-obtained-orphan-drug-designation-from-the-us-fda-for-the-treatment-of-gcgej-302515493.html
- Alphamab Oncology Presented Multiple Clinical Data of Anti-HER2 Biparatopic ADC JSKN003 at the 2025 ASCO Annual Meeting. PR Newswire. June 2, 2025. Accessed August 1, 2025. https://prnmedia.prnewswire.com/news-releases/alphamab-oncology-presented-multiple-clinical-data-of-anti-her2-biparatopic-adc-jskn003-at-the-2025-asco-annual-meeting-302471380.html
- Key Statistics for Ovarian Cancer. American Cancer Society. Accessed November 1, 2025. https://www.cancer.org/cancer/types/ovarian-cancer/about/key-statistics.html#:~:text=About%2020%2C890%20women%20will%20receive,Cancer%20Facts%20&%20Figures%202025.
