Preliminary result of a phase Ib study: Efficacy and safety of FG-M108 plus gemcitabine/nab-paclitaxel as first-line (1L) treatment in patients with Claudin18.2-positive locally advanced unresectable or metastatic (LA/m) pancreatic cancer.

729 Background: FG-M108, an ADCC-enhanced anti-CLDN18.2 monoclonal antibody, showed significant efficacy in 1L treatment of gastric cancer. Herein, we report the safety and efficacy results of FG-M108 in 1L treatment of pancreatic cancer (cohort C2&D2). Methods: In this open-label, multicenter phase I/II study patients received FG-M108 (cohort C2: 300mg/m 2 or cohort D2: 600mg/m 2 Q3W) plus gemcitabine (1000mg/m 2 , d1, d8, Q3W) and nab-paclitaxel (125mg/m 2 , d1, d8, Q3W). Eligible patients were those with CLDN18.2 positive (IHC 1+/2+/3+≥10%) previously untreated LA/m pancreatic cancer. The primary endpoint were the incidence of adverse events (AEs) and preliminary clinical efficacy (ORR, DCR, DOR, PFS, and OS). Results: As of Sep 5 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 (IHC 2+/3+≥40%). Out of 50 patients, 44 patients had at least one tumor assessment after baseline and included in the efficacy analysis set. The results of ORR and DCR in cohort C2 were 32.4% and 100.0%, while that in cohort D2 were 30.0% and 90.0%, respectively. In cohort C2, the median PFS and median DOR were 6.8 months and 9.8 months, respectively. In the subgroup patients with CLDN18.2 moderate-high expression, the median PFS and median DOR were 7.6 months and 9.8 months, respectively. The median OS has not been reached. FG-M108 related AEs were observed in all patients, with 39 patients (78%) having Grade 3/4 AEs and no FG-M108 related fatal AE was observed. The most common FG-M108 related AEs in cohort C2 & D2 were anemia (56.2% vs 63.6%), nausea (56.4% vs 36.4%), vomiting (48.7% vs 45.5%), and hypoalbuminemia (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 well tolerated with encouraging survival especially in patients with CLDN18.2 moderate-high expression, deserving further investigation. Clinical trial information: NCT04894825 .