Alphamab Oncology has announced encouraging early results from its Phase I/II clinical trial (JSKN033-101) evaluating JSKN033, a novel subcutaneous co-formulation of an anti-HER2 bispecific antibody-drug conjugate (ADC) and a PD-L1 immune checkpoint inhibitor. The data, presented at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) in Houston, USA, showcase a favorable safety profile and promising anti-tumor activity in heavily pre-treated patients with advanced HER2-expressing solid tumors or HER2-mutant non-small cell lung cancer (NSCLC).
JSKN033: A Novel Subcutaneous Immuno-Oncology Approach
JSKN033 is designed to improve upon traditional ADC and immunotherapy combinations, which often require prolonged intravenous infusions and can lead to increased adverse events, impacting drug exposure and patient compliance. By combining Alphamab's subcutaneous PD-L1 inhibitor, Envaforlimab (KN035), with an ADC (JSKN003) in a single, high-concentration subcutaneous formulation, JSKN033 aims to offer a more convenient and tolerable treatment option.
Phase I/II Trial Design and Patient Population
The open-label, multicenter Phase I/II study (NCT06226766) enrolled patients with advanced HER2-expressing solid tumors (IHC 1+) or HER2-mutant NSCLC. As of the data cut-off date (October 14, 2024), 11 patients had been enrolled in the dose escalation phase, receiving JSKN033 monotherapy across five dose levels (1.1 mg/kg to 6.7 mg/kg).
Safety and Efficacy Findings
The most common treatment-related adverse events (TRAEs) were injection site reactions, all of which were grade 1 and resolved within two weeks with or without antihistamines. No dose-limiting toxicities were observed.
Among the ten efficacy-evaluable patients, three achieved partial responses (PR), and five had stable disease (SD), resulting in an 80% disease control rate (DCR). Anti-tumor activity was observed starting at the 4.5 mg/kg dose level. Notably, the three patients who achieved PR did so at their first post-baseline scans. These included:
- A patient with HR-positive/HER2-negative breast cancer who had received four or more prior lines of therapy (5.6 mg/kg dose).
- A patient with HER2-mutated NSCLC that had progressed after prior immunotherapy, chemotherapy, and HER2-TKI treatment (5.6 mg/kg dose).
- A patient with triple-negative breast cancer who had previously received Nab-Paclitaxel and radiotherapy (6.7 mg/kg dose).
Seven patients remained on treatment at the data cut-off date.
Implications and Future Directions
These early data suggest that JSKN033 has a favorable safety profile and demonstrates encouraging anti-cancer activity in heavily pre-treated patients. The results support further investigation of JSKN033 as a potential treatment option for patients with HER2-expressing or HER2-mutated cancers. The subcutaneous formulation offers the potential for improved patient convenience and compliance, which could lead to better treatment outcomes. Further studies are needed to confirm these findings and to determine the optimal dose and schedule for JSKN033.
