675P - Evaluation of the safety and efficacy of JSKN003 in patients with advanced HER2-positive (IHC 3+) solid tumors (excluding breast cancer)

Background

JSKN003 is a novel HER2-directed antibody-drug conjugate (ADC) conjugated to a topoisomerase I inhibitor via a dibenzocyclooctyne tetrapeptide linker on the glycans of a humanized bispecific antibody. JSKN003-101 and JSKN003-102 is dose escalation and expansion studies in Australian and Chinese patients (pts) with metastatic solid tumors.

Methods

This is pooled analysis from pts enrolled in JSKN003-101 and JSKN003-102 with histologically documented HER2-positive (IHC 3+) solid tumors who failed prior systemic therapies, received JSKN003 monotherapy intravenously Q3W. The objectives were safety and efficacy of JSKN-003.

Results

As of 15^th Mar 2024, 24 pts (7 CRC, 5 GC, 3 ESCA, 2 OC, 2 BTC, and 5 others) were enrolled and JSKN003 dosed across 6 dose levels, including 2.1 mg/kg, 4.2 mg/kg, 5.2 mg/kg, 6.3 mg/kg, 7.3 mg/kg and 8.4 mg/kg. 10 pts (41.7%) received ≥ 3 prior lines of therapy,6 pts(25%) received anti-HER2 ADC. The median duration of treatment was 13.9 (range,9.4,19.8) weeks, and 20 pts (83.3%) remained on treatment. Treatment-related adverse events (TRAEs) occurred in 23 pts (95.8%), and the mostly common grade 1 and 2 TRAEs were diarrhea (62.5%) and nausea (58.3%), infusion related reaction (29.2%), fatigue (25.0%).5 pts (20.8%) experienced grade ≥3 TRAEs, were neutropenia (8.3%), vomiting (4.2%), fatigue (4.2%) and abdominal discomfort (4.2%). 2 pts had interstitial lung disease, grade 2 (occurred in 6.3 mg/kg), both recovered thereafter. No TRAE led to death or discontinuation. 22 pts with tumor assessment, the ORR and DCR were 72.7% (95%CI: 49.8, 89.3) and 95.5% (95%CI: 77.2, 99.9). 5 pts who received prior anti-HER2 ADC, the ORR was 80% and median DOR was more than 30 weeks.

Conclusions

JSKN003 was well tolerated with encouraging preliminary antitumor activity in heavily pretreated pts with advanced HER2-positive (IHC ≥ 3+) solid tumors, which support further clinical development.

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.