Phase II trial of serplulimab combined with gemcitabine plus nab-paclitaxel (GnP) and SBRT for metastatic pancreatic cancer as the first-line treatment.

4160 Background: The addition of anti-PD-1 monoclonal antibody (mAb) to gemcitabine and nab-paclitaxel (GnP) presented limited improvement in objective response rate (ORR) and disease control rate (DCR) for metastatic pancreatic ductal adenocarcinoma (mPDAC) in our previous study. Therefore, we conducted this phase II trial to evaluate the efficacy and safety of anti-PD-1 mAb (Serplulimab) plus GnP chemotherapy and stereotactic body radiotherapy (SBRT) in patients with mPDAC. Methods: Patients with mPDAC without previous treatment were enrolled to receive Serplulimab and GnP plus SBRT (SGSBRT) (intravenous infusion of Serplulimab 200 mg on day 1 every 3 weeks, gemcitabine 1000 mg/m 2 and nab-paclitaxel 125 mg/m 2 on day 1 and day 8, repeated every 3 weeks; SBRT delivered 5 fractions of 6.6 Gy to the primary tumor or 3 fractions of 8 Gy to the metastatic lesion in cycle 2) as the first-line treatment. The primary endpoint was 6-month progression-free survival (PFS) rate. Secondary endpoints included overall survival (OS), PFS, ORR, DCR, and adverse events (AEs). Moreover, the biomarkers such as circulating tumor DNA (ctDNA) and circulating hybrid cells (CHCs), PD-L1 expression, tumor tissue genetic status, cytokine levels, and immune microenvironment were also investigated. Results: As of January 2025, 47 patients have been enrolled and 41 patients have been followed for more than 6 months, with all 47 patients achieving efficacy according to the protocol. The 6-month PFS rate was 78.48%. The ORR was 74.47% (35/47), including 1 complete response (CR) and 34 partial responses (PR), and the DCR was 100%, with 12 stable disease (SD). The median PFS was 8.6 months, and the median OS was 15.5 months. The frequent grade 3 drug-related AEs were neutropenia (20/47, 42.55%), leukopenia (19/47, 40.43%), anorexia (18/47, 38.30%), and fatigue (11/34, 23.40%). The correlation between biomarkers and efficacy and prognosis are under-analyzed. Conclusions: This phase II study has met our preset primary endpoint with 78.48% in 6-month PFS rate, and SGSBRT presented promising efficacy with manageable safety profile and expected antitumor activity. This combination might be a promising option as first-line therapy for Chinese patients with mPDAC. Clinical trial information: ChiCTR2300073237 .