Preliminary results of a phase II study of surufatinib plus sintilimab, nab-paclitaxel and gemcitabine (AG) as first-line therapy in patients (pts) with locally advanced or metastatic pancreatic adenocarcinoma (mPDAC).

Abstract

659 Background: Advanced pancreatic adenocarcinoma (PDAC) had poor survival and limited therapeutic options. Surufatinib is a potent, small-molecule tyrosine kinase inhibitor (TKI), selectively targeting VEGF receptors (VEGFR) 1, 2, and 3, FGFR 1, and CSF-1R. Recent studies showed that small molecule anti-vascular inhibitor combined with a PD-1 inhibitor exhibited encouraging efficacy in PDAC. This study is to assess the efficacy and safety of surufatinib plus sintilimab (an anti-PD-1 antibody),nab-paclitaxel and gemcitabine(AG) as first-line therapy for mPDAC pts. Here we report the preliminary results. Methods: Eligible pts ≥18 years old with histologically confirmed mPDAC, ECOG PS 0-1, with at least one measurable lesion were enrolled. Pts received surufatinib (250mg, orally daily), sintilimab (200mg, I.V., D1, Q3W), nab-paclitaxel (125mg/m2, I.V., D1, D8, Q3W) and gemcitabine (1000mg/m2,I.V.,D1, D8, Q3W). Based on Simon’s Two-stage design, 11 patients would be enrolled in stage 1; if 3 or more responses were observed, the trial would continue to stage 2, and additional 21 patients would be enrolled. The total sample size was 32. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and safety. Results: At cutoff date of Aug 25, 2023, 15 pts were enrolled and received at least one time treatment. Median age was 60 years (range 45-68), male 53.3%, ECOG PS 1 100%, 66.7% of pts had more than 3 sites of metastasis. The most common metastatic sites were lymph nodes (66.7%) and liver (60.0%). 12 pts had received at least one tumor assessment. Six out of 11 evaluable pts responded during stage 1, allowing for enrollment to continue with a planned 21 additional patients in stage 2. Eight pts achieved partial response (PR), 3 pts achieved stable disease (SD), and the confirmed ORR (c-ORR) was 50.0% (6/12) (95% confidence interval [CI]: 21.1-78.9), and the DCR was 91.7% (11/12) (95% CI: 61.5-99.8). The median time to response (TTR) was 2.95 months (95% CI: 2.79-3.06), and median PFS was not reached yet. 15 pts underwent safety evaluation. The most common AEs of all grades were white blood cell count decreased (66.7%), neutrophil count decreased (60.0%), and anemia (53.3%), and grades ≥ 3 were blood cell count decreased (33.3%), neutrophil count decreased (33.3%), and diarrhea (13.3%). Conclusions: Surufatinib plus sintilimab, along with AG showed preliminary anti-tumor activity and manageable toxicity for the 1L treatment of mPDAC. This trial is ongoing and warrants further exploration in mPDAC. Clinical trial information: NCT05481476 .