JSKN003 Shows Promise in HER2-Positive Solid Tumors and Platinum-Resistant Ovarian Cancer
核心洞察
JSKN003 demonstrated a 56.8% objective response rate in heavily pretreated patients with platinum-resistant ovarian cancer (搜索), irrespective of HER2 (搜索) expression.
In HER2 (搜索)-positive solid tumors (搜索), JSKN003 achieved a 75% objective response rate and an 89.3% disease control rate, showcasing encouraging antitumor activity.
The bispecific antibody-drug conjugate exhibited a favorable safety profile in both studies, with manageable adverse events and no treatment-related deaths reported.
Alphamab Oncology (搜索) presented new clinical data at the 2024 European Society for Medical Oncology (ESMO) Congress highlighting the potential of JSKN003, an anti-HER2 (搜索) bispecific antibody-drug conjugate (ADC), in treating platinum-resistant ovarian cancer (搜索) and advanced HER2-positive solid tumors (搜索). The pooled analysis of two Phase I clinical studies conducted in Australia and China suggests 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 (搜索) 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 (搜索) IHC 0 and 68.8% (95% CI: 41.3, 89.0) in those with HER2 expression (IHC 1+, 2+ and 3+).
According to the study, the median duration of treatment was 12.4 weeks (range: 0.7 - 51.0 weeks), with 64% of patients remaining on treatment at the data cutoff. Safety data indicated that 3 patients experienced interstitial lung disease (ILD)/pneumonitis, and 10% experienced grade 3 treatment-related adverse events (TRAEs), the most common being diarrhea (2%) and anemia (2%). No TRAEs led to death.
Qunxian Rao from Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, who presented the data, noted the urgent need for new treatment options for platinum-resistant ovarian cancer (搜索), where previous studies have shown objective response rates of only 4% to 13% with non-platinum chemotherapy alone.
JSKN003 in Advanced HER2-Positive Solid Tumors
The study also evaluated JSKN003 in 29 patients with advanced HER2 (搜索)-positive (IHC 3+) solid tumors (搜索) (excluding breast cancer (搜索)), including colorectal, gastric, and biliary tract cancers. These patients had failed prior standard therapies and received JSKN003 monotherapy.
The ORR among 28 efficacy-evaluable patients was 75%, with a disease control rate (DCR) of 89.3%. In the subset of patients who had received prior anti-HER2 (搜索) ADC treatment, the ORR was 71.4%. The ORRs for gastric and colorectal cancers were 83.3% and 66.7%, respectively.
The median duration of treatment was 23.6 weeks (range: 4.7~52.0 weeks), with 14 patients remaining on treatment at the data cutoff. Grade 3 or higher TRAEs were observed in 20.7% of patients, including decreased neutrophil count (6.9%), vomiting (3.4%), fatigue (3.4%), decreased white blood cell count (3.4%), and decreased appetite (3.4%). No TRAEs led to death.
Lin Shen from Beijing Cancer Hospital, the study presenter, highlighted the encouraging antitumor activity observed in heavily pretreated patients with advanced HER2 (搜索)-positive solid tumors (搜索), particularly in gastrointestinal cancers.
About JSKN003
JSKN003 is an anti-HER2 (搜索) bispecific ADC developed using Alphamab's proprietary Glycan-specific conjugation platform. The company states that JSKN003 has demonstrated better serum stability and a stronger bystander effect compared to other ADCs, potentially expanding its therapeutic window. Alphamab Oncology (搜索) is actively progressing pivotal clinical trials of JSKN003 in advanced HER2 low-expression breast cancer (搜索) in China.