The CLDN18.2 antigen is frequently found in malignant gastrointestinal cancers, including pancreatic cancer. FG-M108 is a human monoclonal antibody specifically targeting CLDN18.2, designed with optimal affinity and enhanced antibody-dependent cellular cytotoxicity. 

A multi-center Phase Ib study (NCT04894825) is currently evaluating FG-M108 in combination with chemotherapy for patients with locally advanced unresectable or metastatic pancreatic cancer. The study focuses on assessing the safety, tolerability, preliminary efficacy, pharmacokinetics, and immunogenicity of this combination.

As of May 10 2024, 46 eligible patients with pancreatic cancer were enrolled and treated with FG-M108 plus AG, with 35 patients received the 300 mg/m3 dose and 11 patients receiving the 600 mg/m3.

Patient characteristics were typical first-line CLDN18.2+ (IHC 1+/2+/3+ ≥ 10%) locally advanced unresectable or metastatic pancreatic cancer.

All patients experienced treatment-emergent adverse events (TEAEs). Among those receiving the 300 mg/m3 dose, 54.3% had grade ≥ 3 TEAEs, while 81.8% of patients receiving the 600 mg/m3 dose had grade ≥ 3 TEAEs.

KOL insights

“FG-M108 plus AG demonstrated an excellent safety profile and promising clinical efficacy as a first-line treatment for patients with CLDN18.2+ locally advanced unresectable or metastatic pancreatic cancer. The safety and efficacy, particularly in terms of progression-free survival (PFS) and overall survival (OS), of FG-M108 plus AG will continue to be evaluated.” –Expert Opinion.

Conclusion

The Phase Ib study (NCT04894825) of FG-M108 combined with chemotherapy in advanced pancreatic cancer shows promise. With 46 patients treated, the 300 mg/m³ dose had a 33.3% ORR and the 600 mg/m³ dose had a 30% ORR, both achieving a 100% DCR. Despite all patients experiencing TEAEs, the safety profile is favorable. Further evaluation of PFS and OS will determine long-term benefits.