1456P - First in human phase I/II trial of claudin 18.2 ADC RC118 in patients with advanced gastric/gastroesophageal junction cancer

Background

Despite recent advancement on Her2 negative gastric/gastroesophageal junction cancer (GC/GEJA), the prognosis remains suboptimal with a median survival of 15 months. Targeting claudin 18.2 (CLDN18.2) has emerged as a validated strategy. RC118 is a potential first-in-class ADC carrying MMAE with significant anti-tumor activity in pre-clinical studies.

Methods

It is an open-label, multi-center, phase I/II study to evaluate the safety and efficacy of RC118 in the treatment of patients (pts) with advanced or metastatic solid tumors. The study design included a dose-escalation phase followed by a cohort expansion phase at 1.5, 2.0, and 2.5 mg/kg. RC118 was administered intravenously every 2 weeks. The primary endpoints were the safety and objective response rate (ORR). A pooled analysis was performed for pts with CLDN18.2 medium/high expression(≥2+ membrane staining intensity in ≥40% tumor cells) GC/GEJA enrolled in escalation and expansion phase.

Results

As of April 8, 2024, a total of 18 GC/GEJA pts with a median age of 60.5 years (range, 38-75) were enrolled. There were 1, 11 and 6 pts enrolled in 1.5, 2.0 and 2.5mg/kg group, respectively. 5 pts (27.8%) had medium CLDN18.2 expression (40%-75%), and 13 (72.7%) with high expression(≥75%). 11 pts (61.1%) had been heavily pretreated (≥2 prior lines). Treatment-related adverse events (TRAEs) were observed in all pts (100%), with 38.9% experiencing grade 3 or higher TRAEs. No treatment-related mortality was reported. The most frequently reported TRAEs included nausea (77.8%), vomiting (77.8%), and decreased appetite (66.7%). Among the 17 pts evaluable for efficacy per RECIST v1.1, the ORR was 47.1% (95% CI: 26.2-69.0%, 8 PRs), and the DCR was 76.5% (95% CI: 52.7-90.4%). The median PFS was 3.9 months (95% CI: 1.6-5.2) with a median follow-up duration of 4.4 months. In the 2 mg/kg cohort, the ORR and DCR were 54.6% (95% CI: 28.0-72.2%, 6 PRs) and 72.7% (95% CI: 39.0-94.0%), respectively. The median PFS was 4.2 months (95% CI: 1.4-5.2).

Conclusions

RC118 exhibits promising efficacy with a manageable safety profile. The ongoing study aims to identify the optimal dose regimen. Also a combination study with toripalimab is in progress.

Clinical trial identification

NCT05205850.

Editorial acknowledgement

Legal entity responsible for the study

RemeGen Co., Ltd.

Funding

RemeGen Co., Ltd.

Disclosure

J. Fang: Financial Interests, Personal and Institutional, Leadership Role: Remegen Co., Ltd. All other authors have declared no conflicts of interest.