Efficacy of Surufatinib & Sintilimab in Advanced GC/GEJC

Anti-PD-1 antibodies plus chemotherapy are established as the primary 1L therapy for advanced gastric/gastroesophageal junction adenocarcinoma (GC/GEJC) in patients with a CPS score ≥ 5. Despite this, GC/GEJC prognosis remains poor. Preclinical investigations have revealed that the combination of surufatinib, a novel kinase inhibitor targeting VEGFR1-3, FGFR, and CSF-1R, with anti-PD-1 antibodies yields synergistic antitumor effects through modulation of the tumor immune microenvironment. Dong-Sheng Zhang, and the team initiated a phase II trial to evaluate the efficacy of surufatinib plus sintilimab in patients with advanced GC/GEJC. This abstract presents the outcomes of part A of this trial. Researchers conducted an inclusive analysis of a single-arm, open-label, single-center phase II trial comprising two parts: part A (second-line therapy) and part B (first-line therapy). In part A, patients aged 18-75 years, HER2-negative, and naive to immune checkpoint inhibitor therapy, who had failed first-line standard therapy, were enrolled. This phase included safety run-in and dose expansion stages. Six patients in the safety run-in received surufatinib at 250mg once daily combined with a fixed dose of sintilimab (200 mg, d1, Q3W). If more than 1 DLT occurred in stage 1, the recommended dose of surufatinib for stage 2 (N=11) would de-escalate to 200 mg, otherwise would maintain as 250mg. The primary endpoint was ORR per RECIST v1.1, with secondary endpoints encompassing DCR, PFS, OS, and safety. If the ORR of part A was ≥ 30%, the trial would progress to Part B (N=44), further evaluating this combination treatment in previously untreated advanced GC/GEJC. About 16 patients (6 in safety run-in; 10 in dose expansion) were enrolled in part A at data cutoff on 8/10/2023. The median age was 56 years; 75% were male, and 69% had ECOG PS 1. The peritoneum (56%) was the most common metastatic site. No dose-limiting toxicities (DLTs) were observed in the safety run-in stage. Among the 16 evaluable patients, 6 achieved partial response (PR), and 4 achieved stable disease (SD). The confirmed overall response rate (ORR) and disease control rate (DCR) per RECIST v1.1 were 40.0% (95% CI: 15.2-64.6%) and 66.7% (95% CI: 38.4-88.2%), respectively. The median duration of response (DOR) was not reached, with 50% of responders estimated to have a response duration ≥ 7.8 months. Median progression-free survival (PFS) and overall survival (OS) were not yet mature. Grade 1-2 treatment-emergent adverse events (TEAEs) were observed in ≥40% of patients, including hypoproteinemia (62.5%), hypertension (50%), proteinuria (50%), and decreased lymphocyte count (43.8%). Grade ≥3 TEAEs reported by 5 patients (31.3%) included increased blood bilirubin (18.8%), hypertension, decreased lymphocyte count, and elevated alanine transaminase (6.3% each). No treatment-related deaths occurred. The study concluded that surufatinib plus sintilimab demonstrated promising preliminary efficacy and a manageable safety profile as a 2L treatment for advanced GC/GEJC. Part B of the trial is ongoing, with further data analysis anticipated to provide additional insights. The trial was sponsored by Sun Yat-sen University Source:  https://meetings.asco.org/abstracts-presentations/229264 Clinical Trial: https://clinicaltrials.gov/study/NCT05235906 Zhang D S, Liu F R, Lu Y X, et al. (2024). “Surufatinib plus sintilimab in patients with advanced gastric/gastroesophageal junction adenocarcinoma (GC/GEJC): A single-arm, open-label, single-center phase II trial.” Presented at ASCO-GI 2024 (Abstract 358).