Updated multicenter phase Ib/II analysis of surufatinib plus sintilimab and capecitabine in previously treated metastatic small bowel adenocarcinoma and appendiceal carcinoma

Background: Small bowel adenocarcinoma (SBA) and appendiceal carcinoma are rare gastrointestinal malignancies with no established second-line standard. Most patients (pts) progress rapidly following FOLFOX-based chemotherapy, and pMMR/MSS tumors derive minimal benefit from PD-1 blockade alone. Surufatinib (Suru), a multi-target tyrosine kinase inhibitor of VEGFR1-3, FGFR1, and CSF-1R, may enhance antitumor immunity primarily through vascular normalization and reprogramming of the immune microenvironment. We previously reported the dose-limiting toxicities, the recommended phase II dose (RP2D) determined in phase Ib, and preliminary efficacy and safety data from 9 pts presented at AACR 2025. Here we present an updated analysis of efficacy and safety in the 15 pts enrolled to date. Methods: This ongoing multicenter, single-arm, phase Ib/II trial enrolls pts with unresectable SBA or appendiceal carcinoma who have progressed after ≥1 prior systemic therapy. Phase Ib used a 3+3 design testing Suru 200 mg p.o. once daily (dose level 1; DL1) and 250 mg p.o. once daily (DL2) on days 1-21, combined with sintilimab (Sin) 200 mg i.v. on day 1 and capecitabine (Cap) 1000 mg/m² p.o. twice daily on days 1-14, every 3 weeks (q3w). In phase II, pts receive Suru at the RP2D (250 mg p.o. once daily, as established in phase Ib) plus Sin and Cap. The primary endpoint for the overall study is progression-free survival (PFS); secondary endpoints include overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Results: 15 pts were enrolled across two centers. Median age was 57.8 years, and 73.3% were female. 7 pts (46.7%) had SBA and 8 (53.3%) had appendiceal carcinoma. Peritoneal metastasis was nearly universal (93.3%), and 46.7% had received ≥2 prior lines of therapy. Best overall response was PR in 1 patient (6.7%), SD in 8 pts (53.3%), and PD in 6 pts (40.0%), yielding an ORR of 6.7% and a DCR of 60.0%. At the data cutoff (January 1, 2026), 10 PFS events and 6 deaths had occurred; median PFS was 3.3 months (95% CI, 2.0-4.5) and median OS was 19.5 months (95% CI, 8.1-31.0). 2 pts had PFS >6 months, and 4 remained alive >12 months. Safety was consistent with prior interim data. 2 pts experienced grade 3 treatment-related adverse events (TRAEs): one with PR developed hypothyroidism and adrenal insufficiency; the other had diarrhea, hand-foot syndrome, and mucositis. All other TRAEs were grade 1-2. No grade 4-5 TRAEs or treatment-related deaths occurred. Conclusions: Suru plus Sin and Cap demonstrated acceptable tolerability and preliminary antitumor activity in pretreated SBA and appendiceal carcinoma. Ongoing enrollment and molecular correlative analyses may clarify durability and identify subgroups most likely to benefit. ClinicalTrials.gov No.: NCT05472948