1433P - A phase I/II study of FG-M108 plus capecitabine and oxaliplatin (CAPOX) as first-line (1L) treatment for patients with CLDN18.2+/HER2- advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma

Background

FG-M108 is an afucosylated IgG1 monoclonal antibody targeting CLDN18.2 with optimal target affinity and enhanced antibody-dependent cellular cytotoxicity (ADCC) activities. FG-M108 has demonstrated superior anti-tumor activity compared with zolbetuximab and excellent safety profile in preclinical studies.

Methods

This phase I/IIa study evaluated the safety and preliminary anti-tumor activity of FG-M108 300 mg/m² Q3W plus CAPOX in patients with HER2- and CLDN18.2+ (IHC1/2/3+≥10%) advanced or metastatic G/GEJ adenocarcinoma. Treatment-emergent adverse events (TEAEs) were categorized by CTCAE v5.0. Efficacy was evaluated every 6 weeks per RECIST1.1.

Results

As of April 19, 2024, 52 patients were evaluated. Most patients had distant metastasis sites including liver, peritoneal and lung (41.1%, 29.4% and 9.8%, respectively). Treatment-emergent adverse events (TEAEs) were mostly grade 1-2 and the most common TEAEs were neutrophil count decreased (76.9%), anemia (73.1%), white blood cell count decreased (67.3%), platelet count decreased (63.5%) and hypoalbuminemia (59.6%). The incidence of serious FG-M108-related AEs was 13.5% and no FG-M108-related grade 4 or 5 AEs were reported. No patients discontinued treatment due to any TRAEs. In patiens with CLDN18.2 medium to high (IHC 2+/3+ ≥ 40%), confirmed ORR and DCR were 77.8% and 97.2%, respectively. One patient achieves a complete response. Median PFS were 9.6 (95%CI, 6.7-NE) months and the median DoR was 8.5 (95% CI, 5.6-NE) months. In patients with low CLDN18.2 expressions (IHC 1+/2+/3+≥10% & 2+/3+ < 40%), mPFS was 5.0 (95%CI, 3.9-5.6) months, which was consistent with the reported efficacy of CAPOX. Moreover, the median PFS of the patients with medium/high CLDN18.2 expression is significantly longer than those of the patients with CLDN18.2 low (HR=0.28). Median overall survival (mOS) has not been reached yet.

Conclusions

In advanced G/GEJ cancer patients with medium to high level of CLDN18.2 expression, FG-M108 plus CAPOX as the first-line treatment showed a manageable safety profile and improved efficacy outcomes as compared to historical CAPOX controls.

Clinical trial identification

NCT04894825.

Editorial acknowledgement

Legal entity responsible for the study

FutureGen Biopharm.

Funding

FutureGen Biopharm.

Disclosure

J. Gong, F. Liu, M. Zhang, S. Zhang, Y. Zhang, X. Liang: Non-Financial Interests, Institutional, Local PI: FutureGen Biopharm. Z. Jin, Y. Li, Y. Yang: Financial Interests, Institutional, Full or part-time Employment: FutureGen Biopharm. L. Shen: Non-Financial Interests, Institutional, Coordinating PI: FutureGen Biopharm.