759P - JSKN003, a HER2-targeting antibody-drug conjugate, in patients with platinum-resistant ovarian cancer: A pooled analysis of two studies

Background

JSKN003 is a bispecific HER2-targeting antibody-drug conjugate (ADC) conjugated to a topoisomerase I inhibitor (TOP1i) via a dibenzocyclooctyne tetrapeptide linker on the glycan of a humanized bispecific antibody. Pre-clinical studies demonstrate strong anti-tumor activity of JSKN003 with superior tolerance and serum stability.

Methods

JSKN003-101 is a dose-escalation and -expansion study in Australian patients (pts) with advanced/metastatic solid tumors. JSKN003-102 is a phase I/II study in Chinese pts with advanced solid tumors. A pooled analysis of both studies was conducted to evaluate the efficacy and safety of JSKN003 in platinum-resistant ovarian cancer (PROC) patients.

Results

As of 5^th April 2024, 27 pts with PROC had received JSKN003 at 4.2 (n = 2), 5.2 (n = 2), 6.3 (n = 21), 7.3 (n = 1) and 8.4 (n = 1) mg/kg. Among the 27 pts, 5 were HER2 IHC 0, 7 were IHC 1+, 13 were IHC 2+, and 2 were IHC 3+. Most pts (16/27, 59.3%) received ≥ 3 prior lines of therapy, 13 (48.1% ) pts had received prior bevacizumab, and 8 (29.6%) pts had received prior PARP inhibitors. The median duration of treatment was 12.0 (range, 0.57 - 47.43) weeks, and 21 pts (75%) remained on treatment. Treatment-related adverse events (TRAEs) occurred in 23 pts (85.2%), the most common TRAEs were anemia (22.2%), nausea (18.5%), diarrhea (18.5%), and vomiting (18.5%), which were mostly grade 1-2. Only 2 pts experienced G3 TRAE, including diarrhea and anemia. No TRAE led to death or treatment discontinuation. 22 pts had at least one post-baseline tumor assessment. The objective response rate (ORR) was 59.1% (13/22, 95%CI: 36.4%, 79.3%), and 86.4% (19/22) pts had tumor shrinkage. The ORR in pts with HER2 expression (IHC 1+, 2+ and 3+) was 61.1% (11/18), and we also had seen 2 out of 4 pts with HER2 IHC 0 achieving PR. The median DOR and PFS, unmature due to insufficient follow up time, were 6.03 months and 9.43 months, respectively.

Conclusions

In heavily pretreated PROC patients, irrespective of HER2 expression, JSKN003 demonstrated acceptable safety and encouraging preliminary efficacy, which supports further clinical development in PROC.

Clinical trial identification

NCT05494918; NCT05744427.

Editorial acknowledgement

Legal entity responsible for the study

Alphamab Oncology.

Funding

Alphamab Oncology.

Disclosure

All authors have declared no conflicts of interest.