Tislelizumab with anlotinib and chemotherapy for second-line treatment of pancreatic ductal adenocarcinoma: A phase II clinical trial.

e16394 Background: Advanced pancreatic ductal adenocarcinoma is a malignant tumor with poor prognosis. At present, chemotherapy is still the standard treatment, however the efficacy is unsatisfied. The lack of second-line treatment options for pancreatic cancer results in progression-free survival often lasting less than 3 months. For pancreatic cancer is an immune desert type of tumor, immunotherapy has not brought breakthrough therapeutic regimen compared to the remarkable data in other tumors.There is still insufficient therapeutic evidence treated with PD-1 antibody in pancreatic cancer. Anlotinib is a tyrosine kinase inhibitor (TKI) with anti-tumor effects. It has been shown the combination of PD-1 and multi-target tyrosine kinase inhibitors can increase immunotherapy efficacy. The purpose of this study is to evaluate the efficacy and tolerability of Tislelizumab combined with Anlotinib, as well as chemotherapy (the choice of the investigator) in second-line treatment of patients(pts) with pancreatic ductal adenocarcinoma. Methods: In this single arm, phase II, prospective exploratory study, it was planned to recruit 30 adult pts with treated pancreatic ductal adenocarcinoma who have never received any PD (L) 1 and TKI. Eligible pts receive 8 cycles of treatment with Tislelizumab (iv, 200mg, Q3W), Anlotinib (PO, 10mg, QD), and chemotherapy (determined by the researchers), followed by maintenance therapy with trastuzumab and anlotinib until disease progression or death. The primary endpoint was median progression-free survival (mPFS), the secondary endpoints were objective response rate (ORR), median overall survival(mOS), disease control rate (DCR), and treatment safety profile. Results: 25 eligible pts were recruited till Jan 2025, At the data cut-off date (Jan, 2025), there were 3 PR (12.0%), 17 SD (68.0%) and 5 PD (20.0%). Therefore, the preliminary ORR was 12.0% (95%CI: 25.5%-31.2%), DCR was 80.0% (95%CI: 59.3%-93.2%). Median PFS was 3.8 months (95% CI, 2.9-4.8) and the 1-year PFS was 5.3% (95%CI: 0.4%-21.6%). mOS was 8.8 months (95%CI: 6.2-11.4) and the 1-year PFS was 14.6% (95%CI: 2.5%-36.5%). The incidence of TRAEs was 44.0% (11/25), and the incidence of grade 3 and above TRAEs was 12.0% (3/25). The most common treatment-related adverse events (TRAEs) were neutropenia, thrombocytopenia, and increased AST/ALT. The immune-related adverse event of concern was hypothyroidism (grade 1/2), which occurred in two pts. Two pts experienced grade 4 obstructive jaundice caused by the progression of the disease. Conclusions: The second-line combination regimen of Tislelizumab with Anlotinib based on chemotherapy demonstrated survival improvement trend and no new safety signals identified in pancreatic cancer. These data suggest Tislelizumab + Anlotinib+Chemo may be a promising novel treatment option for pts with pancreatic cancer. Clinical trial information: NCT05681390 .