Alphamab Oncology presented new clinical data at the 2024 European Society for Medical Oncology (ESMO) Congress highlighting the efficacy and safety of JSKN003, an anti-HER2 bispecific antibody-drug conjugate (ADC), in platinum-resistant ovarian cancer and advanced HER2-positive solid tumors. The results from two pooled analyses of Phase I studies conducted in Australia and China suggest that JSKN003 could offer a new treatment option for patients with limited alternatives.
JSKN003 in Platinum-Resistant Ovarian Cancer
The pooled analysis included 50 patients with platinum-resistant ovarian cancer (PROC) who had received JSKN003 across various dose levels. The objective response rate (ORR) among 44 efficacy-evaluable patients was 56.8% (95% CI: 41.0, 71.7), with 88.6% showing tumor shrinkage. Notably, the ORR was 52.9% (95% CI: 27.8, 77.0) in patients with centrally confirmed HER2 IHC 0 and 68.8% (95% CI: 41.3, 89.0) in those with HER2 expression (IHC 1+, 2+ and 3+).
"These data support further clinical exploration of JSKN003 in this population," the researchers concluded, emphasizing the potential benefit irrespective of HER2 expression levels. The median duration of treatment was 12.4 weeks (range: 0.7 – 51.0 weeks).
Ovarian cancer is a significant threat to women's health, often diagnosed at an advanced stage with high recurrence rates. Approximately 70% of ovarian cancer cases recur after treatment, progressing to platinum resistance. Current NCCN guidelines recommend non-platinum cytotoxic drugs and targeted monotherapy for platinum-resistant cases, but the objective response rates with non-platinum chemotherapy alone are only 4% to 13%, underscoring the need for new treatments.
JSKN003 in Advanced HER2-Positive Solid Tumors
Another pooled analysis evaluated JSKN003 in 29 patients with advanced HER2-positive (IHC 3+) solid tumors (excluding breast cancer), including colorectal, gastric, and biliary tract cancers. The ORR among 28 efficacy-evaluable patients was 75.0%, and the disease control rate (DCR) was 89.3%. In the subset of patients who had received prior anti-HER2 ADC treatment, the ORR was 71.4%.
"Encouraging antitumor activity was observed in heavily pretreated patients with advanced HER2-positive solid tumors," the researchers stated. The median duration of treatment was 23.6 weeks (range: 4.7~52.0 weeks).
Safety and Tolerability
In the PROC study, 3 patients experienced interstitial lung disease (ILD)/pneumonitis. Grade 3 treatment-related adverse events (TRAEs) occurred in 10.0% of patients, with diarrhea (2.0%) and anemia (2.0%) being the most common. In the HER2-positive solid tumor study, 20.7% of patients experienced grade 3 or higher TRAEs, including decreased neutrophil count (6.9%), vomiting (3.4%), and fatigue (3.4%). No TRAEs led to death in either study, indicating a manageable safety profile.
About JSKN003
JSKN003 is an anti-HER2 bispecific ADC developed using Alphamab’s Glycan-specific conjugation platform. It has demonstrated better serum stability and a stronger bystander effect compared to other ADCs, potentially expanding its therapeutic window. Alphamab Oncology is actively conducting multiple clinical studies of JSKN003 in Australia and China, including a pivotal clinical trial in advanced HER2 low-expression breast cancer in China.
