Surufatinib combined with TAS-102 in third- or later-line therapy of patients with metastatic pancreatic cancer (mPDAC): An open-label, single-arm, phase II study.

e16297 Background: Patients (pts) with mPDAC refractory to FOLFIRINOX and AG have limited therapeutic options. TAS-102 is an orally administered combination of a thymidine-based nucleic acid analogue, trifluridine, and a thymidine phosphorylase inhibitor, tipiracil hydrochloride, and may have activity in 5-FU resistant malignancies. Overexpression of VEGF has been reported in pancreatic cancer and anti-angiogenesis regimens have shown clinical benefits in mPDAC. Surufatinib is a potent, small-molecule tyrosine kinase inhibitor (TKI), selectively targeting VEGFR 1, 2, and 3, FGFR 1, and CSF-1R. This study aimed to assess the efficacy and safety of orally surufatinib combined with TAS-102 in third- or later-line mPDAC. Here we report the preliminary results. Methods: This tiral enrolled pts with histologically confirmed PDAC, ECOG PS 0-1, at least one measurable lesion and have received ≥2 prior chemotherapy regimens in an advanced setting. Pts were treated with surufatinib (250mg once daily) and TAS-102 (35 mg/m 2 twice daily on days 1–5 and 8–12 of each 28-day cycle). The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. Results: From 01/2023 to 12/2023, 17 pts were enrolled (median age 60, 58.8% male). All pts have an ECOG PS 1 and 88.2% had more than 3 sites of metastases. The most common metastatic sites were peritoneum (64.7%), liver (52.9%) and lymph nodes (52.9%), 52.9% of pts had ≥3L prior therapy and 64.7% with primary site on pancreatic body and tail. At the cutoff data on December 20, 2023, one patient continued to receive surufatinib and TAS-102, 11 pts were included in the efficacy analysis. The ORR was 27.3% (95% CI: 6.0-61.0%), with 3 pts achieved partial response (PR). SD was 1(9.1%) with a DCR of 36.4% (4/11) (95% CI: 10.9-69.2%). The median PFS was 3.19 mo (95%CI 1.91-3.94) and PFS rate at 3 months (PFSR 3mon ) was 54.5%. Among the 8 pts without liver metastases, the ORR was 37.5% (3/8) (95% CI: 8.5-75.5%) and the DCR was 50.0% (4/8) (95% CI: 15.7-84.3%), the median PFS was 3.56 mo (95%CI 2.14-NA) and PFSR 3mon was 62.5%. All 17 pts experienced treatment-related AEs (TRAEs), with the most common AEs of all grades were hematological including leukopenia (47.1%), neutropenia (41.2%), lymphopenia (41.2%), bilirubin increased (35.3%) and hypoalbuminemia (29.4%). Grades ≥ 3 were neutropenia (23.5%), lymphopenia (17.6%) and anemia (11.8%). Conclusions: Surufatinib combined with TAS-102 in third- or later-line mPDAC showed encouraging anti-tumor activity and acceptable safety profile, especially in pts without liver metastasis. This trial is ongoing and further molecular biomarkers exploration are warranted. Clinical trial information: NCT05481463 .