FG-M108 plus nab-paclitaxel and gemcitabine (AG) as first-line (1L) treatment for patients with Claudin-18.2 (CLDN18.2) positive locally advanced unresectable or metastatic pancreatic cancer (PC): Preliminary results from the phase 1b study.

Abstract

4142 Background: PC is one of the most lethal cancers with limited treatment options and poor outcomes. The CLDN18.2 antigen is frequently expressed in malignant gastrointestinal cancers including pancreatic cancer. FG-M108 is a human monoclonal antibody specifically targeting CLDN18.2 with optimal affinity and enhanced antibody-dependent cellular cytotoxicity. Methods: A multi-center phase 1b study of FG-M108 (NCT04894825) is ongoing, with one cohort evaluating the safety, tolerability, preliminary efficacy, pharmacokinetics, and immunogenicity of FG-M108 plus AG in patients with locally advanced unresectable or metastatic PC. Only patients with positive CLDN18.2 expression (IHC 1+/2+/3+≥10%) were eligible. This cohort of patients received FG-M108 (intravenous, 300 mg/m2 day 1) plus gemcitabine (intravenous, 1000 mg/m2, days 1 and 8) and nab-paclitaxel (intravenous, 125 mg/m2, days 1 and8) every 3 weeks until disease progression, unacceptable toxicity, or discontinuation. The primary safety endpoint was the incidence of adverse events (AEs) and the secondary efficacy endpoints included objective response rate (ORR), disease control rate (DCR), duration of response, progression-free survival (PFS), and overall survival (OS). Responses were assessed by RECIST 1.1 every 6 weeks. AEs were graded using CTCAE v5.0. Results: As of January 15, 2024, 31 patients received 300 mg/m2 FG-M108 plus chemotherapy. The most common FG-M108 related AEs were nausea (43.5%), emesis (30.4%), neutropenia (21.7%), and anemia (21.7%). The most common grade ≥3 AEs of any cause were neutropenia (26.1%). FG-M108–related serious AEs occurred in 29.0% of patients. No FG-M108–related grade 4 or 5 AEs and no treatment-related deaths were reported. Median PFS and median OS have not been reached yet. Of the 14 patients who received tumor evaluation at least once, ORR was 50.0% (7/14) and DCR was 100% (14/14). Conclusions: FG-M108 plus AG showed excellent safety profile and promising clinical efficacy as 1L treatment for patients with CLDN18.2+ locally advanced unresectable or metastatic PC. The safety and efficacy, especially PFS and OS, of FG-M108 plus AG treatment will be further evaluated. Clinical trial information: NCT04894825 .