Efficacy and safety of surufatinib (Sur) plus paclitaxel (Pac) as second line (2L) treatment for advanced gastric cancer (aGC): Final results from a phase 2 trial.

Abstract

4028 Background: Standard chemotherapy (ChT) provides unsatisfactory efficacy for patients with aGC in the 2L setting. Recent studies have suggested improved efficacy with an antiangiogenic agent plus Pac. Although ramucirumab plus Pac have been approved as a 2L treatment, access to this combination regimen is limited in China. Sur is a potent VEGFRs, FGFR1 and CSF-1R inhibitor. This trial is aimed to assess the efficacy and safety of Sur plus ChT as a 2L treatment for aGC. Our previous report (ASCO-GI 24) revealed promising anti-tumor activity of this regimen. Now we are presenting the final analyses including long-term survival results. Methods: This single-arm, phase 2 clinical trial enrolled patients with HER2-negative aGC who had failed standard first-line treatment. Eligible patients received Sur (250mg, po, qd) plus Pac (150mg/m 2 , iv, d1) at 21-day cycles for 6 cycles, followed by maintenance with single-agent Sur until disease progression or intolerable toxicity. Tumor responses were assessed every 6 weeks by investigators per RECIST v1.1. The primary endpoint was ORR, and secondary endpoints were DCR, PFS, OS, and safety. Results: As of Dec 20, 2024, of the 35 patients enrolled, median age was 65 (range: 33-75), 26 (74.3%) were male, 31 (88.6%) had an ECOG PS of 1, 12 (34.3%) had positive PD-L1 (defined as CPS ≥1), and 26 (74.3%) had received 1L immunotherapy (IO). Seven (20.0%) patients had primary GEJC, and all patients had stage IV disease, with lymph nodes (23, 65.7%), liver (16, 45.7%) and peritoneum (14, 40.0%) being the most common metastatic sites. Tumor response assessments were available in 32 patients, the ORR was 25.0% and DCR was 87.5%. Primary GEJC (42.9% vs 20.0%, P = 0.327) and baseline liver metastases (40.0% vs 11.8%, P = 0.106) seemed correlated to a better ORR, while baseline peritoneal metastases (8.3% vs 35.0%, P = 0.204) the reverse. With a median follow-up of 12.6 (95% CI: 10.4-14.9) months (mo), the mPFS was 5.7 (95% CI: 4.7-6.93) mo and the mOS was 10.8 (95% CI: 7.0-17.2) mo. Within the subgroup patients who had IO exposure in the 1L setting (n = 26), the ORR was 25.0%, the DCR was 91.7%, the mPFS was 5.9 (95% CI: 4.7-10.5) mo, and the mOS reached 14.4 (95% CI: 8.5-NR) mo. Treatment-related adverse events of grade ≥3 included neutropenia (40.0%), leukopenia (34.3%), hypertension (11.4%), and proteinuria (5.7%). There were no treatment-related serious adverse events or on-treatment deaths. Conclusions: These encouraging long-term efficacy results and the manageable safety profile suggested a preferable position of Sur plus Pac as the 2L treatment for aGC, notably, following the current standard 1L IO-containing regimens. Clinical trial information: ChiCTR2200063336 .