TQB2868 combined with anlotinib and nab-paclitaxel plus gemcitabine as first-line treatment for metastatic pancreatic cancer: A prospective, multicenter, single-arm, phase 2 study.

4159 Background: Chemotherapy currently serves as the cornerstone for treating metastaticPancreatic Ductal Adenocarcinoma Cancer (mPDAC). Nevertheless, the survival of patients with mPDAC remains poor. Besides, the efficacy of single-agent immune checkpoint inhibitors or antiangiogenesis in the treatment of mPDAC is not satisfying. Therefore, it is important to explore combination therapy options for patients with mPDAC. TQB2868 injection is a bifunctional fusion protein that targets PD-1 and TGF-βRII. This trial was conducted to evaluate the effectiveness and safety of TQB2868 combined with anlotinib and nab-paclitaxel plus gemcitabine for mPDAC. Methods: This was a prospective, multicenter, single-arm phase II trial. Eligible pts were those who aged over 18 years, histologically or cytologically confirmed PDAC, have not received treatment before and radiographically showed distant metastases and measurable lesions. Patients received TQB2868 (300mg, I.V, D1,15) and Anlotinib (10mg, P.O, QD, D1-14), in addition to nab-paclitaxel (125mg/m 2 , I.V,D1,8,15) and gemcitabine (1.0g/m 2 , I.V, D1,8,15), administered over a 28-day treatment cycle.The primary endpoint was Progression-free Survival (PFS), Secondary end points included objective response rate (ORR) and disease control rate (DCR), overall survival (OS) and safety. The biomarker TGF-β1 was analyzed as exploratory results (NCT06767813). Results: 40 pts were enrolled and received TQB2868 combination regimen therapy, and the last follow-up time was January 10, 2025. 36 pts were eligible for response evaluation. With median follow-up duration of 5.9 months, the median PFS and OS have not been reached, with 6-month PFS and OS rates of 86% and 95%, respectively. The ORR was recorded at 63.9% (23/36) (95% CI, 46.2%-79.2%), with 23 pts achieving partial response. The DCR was 100% (36/36) (95% CI, 90.3%-100%). The most common TRAEs were neutropenia, thrombocytopenia, leukopenia, and anemia. Grade 3 TRAEs were reported in 52.5% pts (21/40). In exploratory analysis, the inhibition rate of TGFβ1 was over 90% in most cases after administration, with little to no rebound. Conclusions: TQB2868 combination regimen as first-line treatment was demonstrated to be tolerable, with promising anti-tumor activity in mPDAC. Clinical trial information: NCT06767813 .