A phase II study of fruquintinib plus sintilimab as a second-line therapy for advanced gastric and gastroesophageal junction adenocarcinoma (GC/GEJC): Updated results.

407 Background: Preliminary results of the open-label, single-arm phase II study (NCT05625737) had demonstrated the combination of fruquintinib and sintilimab as a second-line therapy had a promising anti-tumor activity and an acceptable safety profile in pts with advanced GC/GEJC (ASCO-GI 2024. Poster 332). Here, we update the results with a focus on subgroup analyses. Methods: Patients (pts) aged 18-75 years who were HER2-negative and had failed first-line standard treatment were enrolled. Eligible pts received 4mg of fruquintinib orally once daily on days 1-14 and 200 mg of sintilimab intravenously on day 1, with treatment repeated every 3 weeks. An optimal Simon two-stage design was employed. The primary endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results: At data cut-off (August 25, 2024), 29 pts (7 in the first stage; 22 in the second stage) with median age 51 (range 33–73) years old had been enrolled. 41.4% were male, 37.9% had ECOG PS 1, 69% had lymph node metastasis and 72.4% had previously received immunotherapy. Among the 24 efficacy evaluable pts, the ORR was 33.3% (95% CI 15.6–55.3) and DCR was 66.7% (95% CI 44.7–84.4). After a median follow-up of 13.14 months, the median PFS was 5.13 (95% CI: 2.73–7.03) months and OS result was pending maturity. Pts who had lymph node metastasis exhibited higher ORR compared to pts without lymph node metastasis (ORR-47.1 vs 0%). In particular, pts without prior immunotherapies were more likely to achieve higher response rate (37.5 vs 33.3%) and had an obvious trend for longer PFS than pts with prior immunotherapies (9.00 vs 5.13 months). Majority of treatment-emergent adverse events (TEAEs) were grade 1-2 and the most frequently reported ones (≥20%) were white blood cell decreased (33%), hypertriglyceridemia (25%), lymphocyte count decreased (21%), abdominal pain (21%) and decreased appetite (21%). Grade 3/4 TEAEs occurred in only one patient, consisting of increased blood bilirubin levels, aspartate transaminase elevation, and alanine transaminase elevation. Conclusions: Fruquintinib combined sintilimab was well tolerated, with encouraging antitumor activity as second-line treatment for advanced GC/GEJC, especially in pts without prior immunotherapies. Further studies in larger cohorts to validate these findings are warranted. Clinical trial information: NCT05625737 .