Efficacy and safety of second-line therapy by envafolimab combined with anlotinib and S-1 in pancreatic cancer patients: A single-arm, phase II clinical trial.

e16385 Background: Pancreatic adenocarcinoma carries a grim prognosis, and there are few recognized effective second line and later line treatment strategies. Therefore, This trial aims to investigate the effects of envafolimab, the world’s first subcutaneously injectable anti-PD-L1 antibody approved by China’s NMPA, in combination with anlotinib and S-1 as a second line and later line treatment in pancreatic cancer patients. Methods: Pancreatic cancer patients were recruited. Envafolimab was administered at 400mg every 3 weeks subcutaneously , anlotinib was administered 12mg, P.O, QD, D1-14, and S-1 was administered at 40 mg/m 2 , P.O, BID, D1-14. This method was repeated every 21 days, and the therapeutic effect was evaluated every 2 cycles. The primary outcome was the objective response rate (ORR).Secondary end points included disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety. Results: Overall, 16 patients were enrolled in this study and the median follow-up time was 5.63 months, all were eligible for response evaluation. Characteristics were as follows: median age of 63 years, male/female 56.3%/43.8%, ECOG PS 0-1/2-3 18.8%/81.3%, MSS/MSI-H/NE 50.0%/0.0%/50.0%, liver metastasis 62.5%. All pts received ≥ 2 cycles of treatment regimen, and the median medication cycle was 5 (2-14) cycles. 25.0% patients had received second-line therapy, 75.0% patients had received third or above line. The partial response (PR), stable disease (SD) or progressive disease (PD) was 12.5%, 62.5%, or 12.5%, respectively.The ORR was 12.5% (95% CI 1.6%-38.3%) and the DCR was 75.0% (95% CI 35.4%-84.8%) in the evaluable population. The median progression-free survival (mPFS) was 6.97 (95% CI 3.45 -13.83) months, and the median overall survival (mOS) was not reach (95% CI 2.60-NE) months. Safety profile of envafolimab combined with anlotinib and S-1 indicated that the treatment related adverse events (TRAEs) were 25%, included fever (6.25%), mouth ulcers (6.25%), elevated bilirubin (6.25%), leukopenia (6.25%). No grade 3 or above adverse events occurred. Conclusions: This study suggests the advantage of envafolimab combined with anlotinib and S-1 demonstrated encouraging efficacy and tolerable adverse reactions among patients with advanced pancreatic cancer patients. Clinical trial information: ChiCTR2300068595 . Best overall responses (BOR) of third or above line subgroup or ECOG PS 2-3 subgroup. third or above line, N=12, N(%) ECOG PS 2-3 N=13, N(%) CR 0 0 PR 2 (16.67%) 1 (7.69%) SD 8 (66.67%) 10 (76.92%) PD 1 (8.33%) 0 NE 1 (8.33%) 2 (15.38%) ORR 16.67% 7.69% DCR 83.33% 84.61%