On March 18, 2025,Alphamab Oncology announced that anti-HER2 biparatopic antibody-drug conjugate (ADC) JSKN003 has been granted Breakthrough Therapy Designation by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA). The designation is for the treatment of platinum-resistant recurrent epithelial ovarian cancer (PROC), primary peritoneal cancer, or fallopian tube cancer, not restricted to HER2 expression levels.
The grant of Breakthrough Therapy Designation is based on the pooled analysis of two clinical studies, JSKN003-101 and JSKN003-102. JSKN003-101 (NCT05494918) is an open-label, multicenter, dose-escalation Phase I clinical study conducted in Australia, enrolling patients with advanced solid tumors expressing HER2 (IHC≥1+) or with HER2 mutations. JSKN003-102 (NCT05744427) is a Phase I/ II study conducted in China. The Phase I part enrolled patients with histologically confirmed HER2 expression (IHC≥1+) or HER2 mutations advanced solid tumors. The Phase II part enrolled patients with advanced solid tumors regardless of HER2 expression or mutation status.
Preliminary data from the pooled analysis of these two studies were presented at the 2024 European Society for Medical Oncology (ESMO) Congress.
As of July 15, 2024, 50 patients with PROC had received JSKN003 across five dose levels, among which 2 patients at the dose of 4.2mg/kg, 2 patients at the dose of 5.2mg/kg, 44 patients at the dose of 6.3mg/kg, 1 patient at the dose of 7.3mg/kg, and 1 patient at the dose of 8.4mg/kg. Among the enrolled 50 patients based on the central laboratory testing, there were 17 patients with HER2 expression (IHC 1+, 2+ and 3+) (only 2 patients with HER2 IHC 3+), 17 patients with IHC 0, and 16 patients had no HER2 results because they had not been tested by July 15. 28 patients (56.0%) had at least three prior lines of systemic treatment, 37 patients (74.0%) had received bevacizumab treatment, and 28 patients (56.0%) had received PARP inhibitor treatment.
The median duration of treatment was 12.4 weeks (range: 0.7 – 51.0 weeks), with 32 patients (64.0%) remained on treatment to the data cut-off date.
Safety: Among all the enrolled 50 patients, 3 patients experienced interstitial lung disease (ILD)/pneumonitis. 5 patients (10.0%) experienced grade 3 treatment-related adverse events (TRAEs), with the most common being diarrhea (2.0%) and anemia (2.0%). No TRAEs led to death.
Efficacy: Among the 44 efficacy evaluable patients who had at least one post-baseline tumor assessment, the objective response rate (ORR) was 56.8%, with 39 patients (88.6%) showing tumor shrinkage. The ORR in patients with centrally confirmed HER2 IHC 0 and HER2 expression (IHC 1+, 2+ and 3+) was 52.9% and 68.8%, respectively. For 33 patients who received prior bevacizumab treatment the ORR was 54.5%, for 26 patients who received prior PARP inhibitor treatment the ORR was 46.2%.
Pooled results have demonstrated that JSKN003 monotherapy has a favorable tolerability and safety profile, with promising efficacy signals in patients with advanced PROC, and the efficacy was observed across patients with (IHC 1+/2+3+) or without (IHC 0) HER2 expression, with or without prior bevacizumab and prior PARP inhibitor.
About JSKN003
JSKN003 is an anti-HER2 bispecific antibody-drug conjugate (bis-ADC), which is developed inhouse with Alphamab’s proprietary Glycan-specific conjugation platform. JSKN003 can bind HER2 on the surface of tumor cells and release topoisomerase I inhibitors (TOPIi) through cellular endocytosis, thereby exert anti-tumor effects. Compared with its ADC counterparts, JSKN003 demonstrated better serum stability and stronger bystander effect, which effectively expands the therapeutic window.
At present, there are still many clinical trials of new anti-cancer technologies in China seeking patients. Consultation on new drugs and technologies, you can contact Beijing South Region Oncology Hospital International Department.
Phone Number：4008803716
Email：myimmnet@163.com
References
1.https://www.cde.org.cn/main/xxgk/listpage/9f9c74c73e0f8f56a8bfbc646055026d
2.https://www.alphamabonc.com/en/
Post time: Mar-18-2025