First-line treatment of QLS31905 plus chemotherapy in patients with pancreatic cancer and gastric cancer: Data from a phase 1b/2 study.

4003 Background: QLS31905, a Claudin18.2/CD3 bispecific antibody, showed manageable safety and encouraging efficacy in Claudin18.2-positive patients (pts) with gastrointestinal tumors in a phase 1 trial. Here we report the safety and efficacy of QLS31905 plus chemotherapy in the first-line treatment of Claudin18.2-positive pts with pancreatic cancer (PC) and gastric cancer (GC). Methods: This phase 1b/2 trial recruited Claudin 18.2-positive (defined as ≥1% of tumor cells with ≥1+ staining intensity) pts with locally advanced unresectable or metastatic PC and GC who had not received systematic anti-tumor therapy. Pts with PC were administered QLS31905 at 350 μg/kg, 500 μg/kg, or 800 μg/kg Q2W or Q3W combined with gemcitabine plus nab-paclitaxel (Cohort 1). Pts with GC were administered QLS31905 at 500 μg/kg or 800 μg/kg Q3W combined with oxaliplatin plus capecitabine (Cohort 2). The primary endpoints were maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) in phase 1b and was objective response rate (ORR) in phase 2. Results: As of Dec 11, 2025, 88 pts with PC and 43 pts with GC were enrolled. No dose-limiting toxicity occurred. MTD was not reached. RP2D was determined as 800 μg/kg Q3W for both pts with PC and GC. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 63 (71.6%) pts and 26 (60.5%) pts in Cohort 1 and Cohort 2, respectively. Ten pts (11.4%) in Cohort 1 and four pts (9.3%) in Cohort 2 discontinued any of the study treatment due to TRAEs. No QLS31905-related death occurred in both cohorts. In 82 efficacy-evaluable pts with PC, ORR and disease control rate (DCR) was 59.8% (95% confidence interval [CI], 48.34%-70.44%) and 89.0% (95% CI, 80.18%-94.86%), respectively. Median progression-free survival (PFS), duration of response (DoR), and overall survival (OS) was 8.74 months (95% CI, 7.16-10.71), 8.94 months (95% CI, 5.32-not evaluable [NE]), and 15.87 months (95% CI, 13.14-NE), respectively. In 15 pts with low Claudin18.2 expression in Cohort 1, ORR, DCR, median PFS, and median OS was 60.0% (95% CI, 32.29%-83.66%), 93.3% (95% CI, 68.05%-99.83%), 11.04 months (95% CI, 7.33-NE), and 15.61 months (95% CI, 3.98-NE), respectively. In 43 efficacy-evaluable pts with GC, ORR and DCR was 74.4% (95% CI, 58.83%-86.48%) and 93.0% (95% CI, 80.94%-98.54%), respectively. Median PFS and DoR was 10.09 months (95% CI, 6.87-NE) and not reached, respectively. In nine pts with low Claudin18.2 expression in Cohort 2, the ORR, DCR, median PFS, and 9-month PFS rate and was 77.8%, 100%, not reached, and 83.33%, respectively. Conclusions: QLS31905 plus chemotherapy in first-line treatment for Claudin18.2-positive pts with PC and GC showed manageable safety and potential efficacy. A phase 3 trial is ongoing to further confirm the efficacy and safety of QLS31905 in pts with PC. Clinical trial information: NCT06041035 .