First-line serplulimab and bevacizumab combined with nab-paclitaxel/gemcitabine followed by mFOLFOX in advanced pancreatic cancer: A phase II trial.

4162 Background: Patients with advanced pancreatic cancer (PC) have a poor prognosis, as this 'cold' tumor shows limited responsiveness to mono-immunotherapy. Chemotherapy may improve the efficacy of immunotherapy by reshaping the tumor immune microenvironment. We conducted a phase II trial to assess the anti-tumor activity and safety of first-line serplulimab (anti-PD-1) and HLX04 (a bevacizumab biosimilar) combined with nab-paclitaxel plus gemcitabine (nab-P/Gem), followed by modified FOLFOX (oxaliplatin, leucovorin, and 5-fluorouracil; mFOLFOX), in patients with locally advanced or metastatic PC. Methods: This single-arm phase II trial enrolled 37 patients with histologically or cytologically confirmed unresectable locally advanced or metastatic pancreatic ductal adenocarcinoma (NCT06393166). The study aims to increase the objective response rate (ORR) of the first-line sequential nab-P/Gem followed by mFOLFOX (nab-P/Gem-mFOLFOX) regimen from 50% to 68% with the addition of serplulimab and HLX04. The study employed Simon's minimax two-stage design, with a total of 23 patients achieving objective responses, thereby meeting the predefined primary endpoint. Secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and safety. Results: Among the 37 patients analyzed, the average age was 62 years, and 22 patients (59.5%) were male. At baseline, patients had an adequate nutritional and performance status, with a mean BMI of 21.6 kg/m 2 . Distant organ metastases were present in 34 patients (91.9%), with the liver being the most common site (n = 26, 70.3%). The confirmed ORR was 67.6% (95% CI, 49.5-82.6), including 1 patient with a complete response (CR), meeting the primary endpoint. Only 1 patient had progressive disease (PD) as the best response, yielding a DCR of 97.1% (95% CI, 84.7-99.9). As of the data cutoff in November 2024, the median follow-up was 6.1 months. The median PFS was 10.5 months (95% CI, 9.7-not reached), with a 6-month PFS rate of 80.0% (95% CI, 65.5-97.7). The median time to response (TTR) was 1.5 months, and the median duration of response (DOR) was 9.3 months. The OS remains immature. The incidence of treatment-related adverse events (TRAEs) was 83.8%, with grade ≥3 TRAEs occurring in 46.0% of patients. Hematologic toxicities were the most common treatment-emergent adverse events (TEAEs), and no fatal AE were observed. Overall, the treatment was manageable, and no new safety signals were identified. Conclusions: First-line serplulimab and HLX04 combined with nab-P/Gem-mFOLFOX demonstrates clinical feasibility and promising preliminary outcomes in advanced PC. Further follow-up is required to confirm the survival benefits, and following analyses are needed to explore the mechanisms underlying the efficacy of this novel regimen. Clinical trial information: NCT06393166 .