QL1706 combined with nab-paclitaxel and gemcitabine as first-line treatment for locally advanced or metastatic pancreatic adenocarcinoma: A prospective, multicenter, single-arm phase II study.

4203 Background: First-line chemotherapy with nab-paclitaxel and gemcitabine (AG) provides limited efficacy in advanced pancreatic ductal adenocarcinoma (PDAC). QL1706, a bifunctional antibody targeting PD-1 and CTLA-4, has demonstrated favorable efficacy and safety. This phase II study evaluated the efficacy and safety of QL1706 plus AG as first-line treatment in patients with locally advanced or metastatic PDAC. Methods: Adult patients with histologically confirmed, unresectable locally advanced or metastatic PDAC, ECOG performance status 0–1, no prior systemic therapy, and at least one measurable lesion were enrolled. Patients received QL1706 (5 mg/kg, IV, day 1) in combination with nab-paclitaxel (125 mg/m², IV, days 1 and 8) and gemcitabine (1,000 mg/m², IV, days 1 and 8) every 3 weeks. Tumor assessments were performed every two cycles. Up to eight cycles were administered, followed by QL1706 maintenance in patients without disease progression. Primary endpoints were objective response rate (ORR) and safety. Results: A total of 30 patients were enrolled. The median age was 59 years (range, 44–74), and 20 patients were male. Primary tumors were located in pancreatic head in 14 (46.7%) and in body or tail in 16 (53.3%). Eight (26.7%) and 22 (73.3%) patients had locally advanced (stage III) and metastatic (stage IV) disease, respectively. Among 26 patients assessed for KRAS mutations, the G12D variant was most prevalent (46.2%), followed by G12R (30.8%) and G12V (23.0%). At data cutoff, after a median follow-up of 5.2 months (range, 4.1–6.8), 18 patients remained on treatment. Of these, 2 underwent curative surgery and 4 transitioned to maintenance therapy. Twelve patients discontinued treatment due to disease progression, including 5 who subsequently died. The median number of treatment cycles administered was 4.5 (range, 2–8) for chemotherapy and 4 (range, 1–8) for QL1706. All patients had at least one post-baseline tumor assessment. Best overall response were complete response in 1(3.3%), partial response in 8 (26.7%), stable disease in 16 (53.3%), and progressive disease in 5 (16.7%).The ORR was 30.0% (95% CI, 14.7–49.4%) and disease control rate was 83.3% (95% CI, 65.3-94.4%). The survival data were not mature by analysis. All patients experienced at least one treatment-related adverse event (TRAE). Grade ≥3 TRAEs occurred in 16 patients (53.3%). The most frequent grade 3–4 TRAEs were neutropenia (23.3%) and leukopenia (20.0%), followed by hypersensitivity reactions (13.3%), thrombocytopenia (6.7%), thromboembolism (6.7%), and pancreatitis (6.7%). No grade 5 TRAEs or treatment-related deaths occurred. Conclusions: QL1706 combined with AG demonstrated promising antitumor activity with a manageable safety profile as first-line treatment for advanced PDAC. Clinical trial information: NCT06750861 .