Continuation of serplulimab-based therapy beyond first progression in advanced gastric/gastroesophageal junction (G/GEJ) cancer: Preliminary results from the SCAFIGC trial.

e16022 Background: Anti-PD-1 in combination with chemotherapy has been confirmed to improve the prognosis of patients with advanced gastric/gastroesophageal junction (G/GEJ) cancer, particularly in those with a PD-L1 combined positive score (CPS) ≥5. However, the efficacy and safety of continuing immune-based therapy after disease progression (PD) in patients who have benefited from first-line immunochemotherapy remain unclear. We conducted a two-stage, phase 2 trial to explore the clinical feasibility of continuing serplulimab (an anti-PD-1 monoclonal antibody)-based therapy beyond first-line progression. Methods: The SCAFIGC trial (NCT05942573) is a multi-center, open-label, randomized phase 2 study comprising two treatment stages. Stage I enrolled histologically confirmed, unresectable, locally advanced, or metastatic G/GEJ cancer patients who were PD-L1 CPS ≥5, HER2 negative, and had not received prior therapy. All patients received 6-8 cycles of serplulimab combined with XELOX (oxaliplatin and capecitabine), followed by maintenance serplulimab plus capecitabine until disease progression, intolerable toxicity, or death. Patients who tolerated stage I treatment and experienced disease progression at least 3 months after treatment initiation were eligible for stage II. These patients were randomized (2:1) to receive serplulimab combined with apatinib and paclitaxel or paclitaxel ± ramucirumab. The primary endpoint was the 6-month progression-free survival (PFS) rate of stage II, which was expected to improve to 63%. Secondary endpoints included PFS, objective response rate (ORR), duration of response (DOR), overall survival (OS), and safety across both stages. Results: As of November 2024, stage I had enrolled 53 patients, most of whom were male (n = 44, 83.02%) with a median age of 62 years, and 32 patients (60.38%) were aged ≥60 years. Among the 46 patients evaluable for tumor response in stage I, the ORR was 52.17% (95% CI: 36.95%-67.11%), with 3 patients achieving complete response (CR), and the disease control rate (DCR) was 82.61% (95% CI: 68.58%-92.18%). The median PFS in stage I was 13.73 months (95% CI: 6.43-not reached), with a 12-month PFS rate of 51.57% (95% CI: 36.22%-73.43%), and four patients had PFS of more than one year at the data cut-off date. Median DOR and OS were not yet mature. Patients tolerated stage I treatment well, with grade ≥3 treatment-related adverse events (TRAEs) reported in 5 patients (9.43%), the most common being decreased neutrophil count (3.77%). Conclusions: Patients with advanced G/GEJ cancer demonstrate promising clinical efficacy and manageable safety after receiving first-line serplulimab combined with chemotherapy. Further follow-up is needed to assess the potential for long-term benefit and to evaluate the efficacy and safety of the stage II treatment. Clinical trial information: NCT05942573 .