Abstract CT146: Sequential treatment with surufatinib combined with gemcitabine and nab-paclitaxel (AG) or AG alone as first-line therapy for locally advanced or metastatic pancreatic ductal adenocarcinoma (mPDAC) after 6 weeks of AG induction therapy: A two-cohort, exploratory phase II study

Abstract Background: PDAC is an extremely aggressive malignancy with limited therapeutic options. Despite current first-line therapies like AG, the 5-year survival rate remains below 5%. Surufatinib (S) is a novel tyrosine kinase inhibitor that selectively targets VEGFR1-3, FGFR1, and CSF-1R. This study aimed to evaluate the efficacy and safety of S plus AG or AG alone as first-line treatment for patients with mPDAC. Methods: This exploratory, phase II trial (NCT05969171) enrolled two cohorts. Eligible patients (pts) with 18-75 years, histologically confirmed mPDAC, with no disease progression after 6 weeks of AG induction therapy (pts with increased SD were also excluded) were assigned to cohort 1 (S 250 mg qd, po, q3w plus AG: nab-paclitaxel 1000mg/m2, iv, d1, d8; gemcitabine 1000mg/m2, iv, d1, d8, q3w) or cohort 2 (AG alone, q3w). The Primary endpoint was PFS. Secondary endpoints included ORR, DCR, OS, and safety. Results: As of December 31, 2025, 26 pts were enrolled in cohort 1 (median age 61. 0 years; 57. 7% male; 50% had ≥1 metastatic organ; median CA19-9 206. 0 U/mL) and 26 pts in cohort 2 (median age 60. 0 years; 65. 4% male; 38. 4% had 1 metastatic organs; median CA19-9 438. 5 U/mL). In cohort 1, 6 pts (23. 1%) achieved PR following 6 weeks of AG therapy, and an additional 14 pts achieved PR during S plus AG treatment, resulting in an ORR of 76. 9%. The median PFS (time from initiation of AG treatment to PD or death) was 13. 96 months (95% CI: 5. 6-22. 3). Subgroup analysis revealed longer mPFS in pts without metastatic organ compared to those with ≥1 metastatic organ (not reached vs. 8. 64 months, p=0. 081) and in pts with a ≥90% reduction in CA19-9 versus those with a 90% reduction (not reached vs. 9. 26 months, p=0. 046). In cohort 2, 8 pts (30. 8%) achieved PR during AG therapy, and 10 additional pts achieved PR with continued AG treatment, yielding an ORR of 69. 2%. The median PFS was 10. 68 months (95% CI: 9. 3-12. 1). Consistent with cohort 1, subgroup analysis showed prolonged PFS in pts with ≤1 metastatic organ versus those with 1 metastatic organs (12. 52 vs. 6. 64 months, p=0. 0083) and in pts with a ≥70% reduction in CA19-9 versus those with a 70% reduction (11. 6 vs. 8. 34 months, p=0. 072). Median OS was not reached in either cohort. Common TEAEs of grade ≥3 in cohort 1 were alopecia (80. 8%), neutropenia (42. 3%), and leukopenia (30. 8%) ; in cohort 2, these were alopecia (76. 9%), leukopenia (34. 6%), and neutropenia (26. 9%). Conclusions: Induction therapy with 6 weeks of AG followed by sequential surufatinib plus AG demonstrated promising efficacy with a manageable safety profile as first-line treatment for mPDAC. This therapeutic strategy may be particularly beneficial for patients without metastatic organs or those who achieve a ≥90% reduction in CA19-9 during treatment. Citation Format: Jialin Li, Miaoyan Wei, Nan Du, Si Shi, Jin Xu, XianJun Yu. Sequential treatment with surufatinib combined with gemcitabine and nab-paclitaxel (AG) or AG alone as first-line therapy for locally advanced or metastatic pancreatic ductal adenocarcinoma (mPDAC) after 6 weeks of AG induction therapy: A two-cohort, exploratory phase II study abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts) ; 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86 (8Suppl): Abstract nr CT146.