A phase Ib/II clinical study of adebrelimab in combination with capecitabine and oxaliplatin for previously untreated patients with advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma.

Abstract

e16065 Background: Immune checkpoint inhibitors (ICIs) have dramatically improved survival in various tumor types by preventing the inhibition of T cells by tumor cells. Adebrelimab is a PD-L1 monoclonal antibody using lgG4 subtype immunoglobulin with superior antitumor activity and safety profile. We conducted this study to investigate whether the addition of adebrelimab to capecitabine and oxaliplatin would further improve clinical outcomes. Methods: This multicenter, single-arm, prospective trial was conducted across 8 academic institutions in China (NCT06776770). Eligible patients were advanced or metastatic gastric cancer/gastroesophageal junction adenocarcinoma with no prior systemic therapy for metastatic disease. The Phase Ib study used a 3+3 design to determine the recommended Phase II dose (RP2D) of adebrelimab with eight 21-day cycles of oxaliplatin (130 mg/m², d1) and capecitabine (1,000 mg/m², twice daily on days 1 to 14, followed by a 7-day rest period). The Phase II trial evaluated efficacy and safety at the RP2D. The primary endpoint was objective response rate (ORR), targeting an improvement from 35% to 55%. Results: From 2024 to 2026, the study had a median follow-up duration of 7.7 months, which did not reach the expected progression-free survival (PFS) time. A total of 15 patients were enrolled during this period, including 3 in the Phase Ib dose-escalation cohort and 12 who have been enrolled to date in the Phase Ⅱ dose-expansion cohort. No dose-limiting toxicities (DLT) were observed during the Phase Ib dose escalation (10 mg/kg to 1200 mg); based on the Phase Ib results, the recommended Phase II dose (RP2D) of adebrelimab was established as 1200 mg Q3W. Common drug-related AEs included hematological toxicities (neutropenia, leukopenia, thrombocytopenia, anemia) and hepatic dysfunction. All were chemotherapy-related with no irAEs observed; all were well controlled with standard interventions, no new AEs or treatment-related deaths reported. Among the Phase Ib cohort, 3 patients were evaluable for efficacy with an objective response rate (ORR) of 66.7%, and 10 patients in the Phase Ⅱ cohort were evaluable for efficacy with an ORR of 60.0%. Conclusions: The results inform clinical decision-making for patients on first-line adebrelimab plus capecitabine and oxaliplatin for advanced gastric cancer. Clinical trial information: NCT06776770 . Variables Adebrelimab 10 mg/kg (N=3) Adebrelimab 20 mg/kg or 1200 mg (N=12) All (N=15) Median Age (years, range) 54(42~57） 61(43~75) 60(42~75) Males 2 7 9 ECOG PS 0/1 3/0 9/3 12/3 PD-L1 CPS < 1 /≥ 1 /≥ 5 0/3/2 1/10/4 1/13/6 Liver metastasis YES/NO 0/3 3/9 3/12 Peritoneal metastasis YES/NO 3/0 7/3 10/3 BOR per RECIST 1.1 CR/PR/SD/PD/NE 0/2/1/0/0 0/6/3/1/2 0/8/4/1/2 ORR/DCR 67%/100% 60%/90% 61%/92%