Preliminary result of a phase Ib study: Efficacy and safety of FG-M108 plus gemcitabine and nab-paclitaxel in patients with Claudin18.2-positive, locally advanced, unresectable, or metastatic pancreatic cancer.

4188 Background: FG-M108, an ADCC-enhanced anti-CLDN18.2 monoclonal antibody, showed significant efficacy in first-line (1L) treatment of gastric cancer. Herein, we report the safety and efficacy results of FG-M108 in 1L treatment of pancreatic cancer (cohort C2 and D2). Methods: In this open-label, multicenter phase I/II study patients received FG-M108 (cohort C2: 300mg/m2 or cohort D2: 600mg/m2 Q3W) plus gemcitabine (1000mg/m2, d1, d8, Q3W) and nab-paclitaxel (125mg/m2, d1, d8, Q3W). Eligible patients were those with CLDN18.2 positive local advanced or metastatic pancreatic cancer who were previously untreated. The primary endpoint were the incidence of adverse events (AEs) and preliminary clinical efficacy (ORR, DCR, DOR, PFS, and OS). Results: As of November 15, 2024, 50 patients were enrolled and received FG-M108+gemcitabine/nab-paclitaxel treatment (39 patients in cohort C2, 11 patients in cohort D2). The median age was 61 (range 30-72). 47 (94%) patients were with CLDN18.2 moderate-high expression. Out of 50 patients, 44 patients had at least one tumor assessment after baseline and included in the efficacy analysis set. The median follow-up time (95%CI) for the 32 patients with CLDN18.2 moderate-high expression was 9.5 months (6.8,11.2) , with a maximum treatment duration of 13 months. In the subgroup of cohort C2 patients with CLDN18.2 moderate-high expression assessed by Independent Review Committee(IRC)—16 patients achieved confirmed PR, and one achieved unconfirmed PR. ORR was 53.1% (34.7,70.9), and DCR was 100.0% (89.1-100.0). The median DOR reached 9.9 months (7.8,NE), and the median PFS reached 9.9 months (7.0,NE) . OS data are not yet mature, with 23 patients still alive, achieving a median OS of 17.4 months (11.0,NE). Treatment-emergent adverse events (TEAE) occurred in 32 patients (100.0%), in which 15 (46.9%) were ≥ grade 3. The most common FG-M108 related AEs in cohort C2 & D2 were nausea (56.4% vs 36.4%), vomiting (48.7% vs 45.5%), and hypoalbuminaemia (46.2% vs 54.5%). Conclusions: The combined therapy of FG-M108 plus chemotherapy as 1L treatment for patients with CLDN18.2 positive pancreatic cancer was generally well tolerated with promising survival (PFS and OS) data especially in patients with CLDN18.2 moderate-high expression, pivatol phase III clinical study will start in 2025 Q2. Clinical trial information: NCT04894825 .