Sugemalimab Plus Chemotherapy Improves Survival in Advanced Gastric Cancer, JAMA

Gastric cancer, including gastroesophageal junction cancer, is one of the most frequently diagnosed cancers globally, with high mortality. Immune checkpoint inhibitors against PD-1 or PD-L1 have been shown to be beneficial in enhancing survival. Sugemalimab, an anti-PD-L1 fully human monoclonal antibody, had earlier shown promising efficacy and safety in phase 1b when administered together with chemotherapy.

The GEMSTONE-303 was a phase 3, double-blind, randomized, placebo-controlled trial in 54 sites in China.A total of 479 unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma patients with PD-L1 CPS ≥5 were enrolled during the period April 9, 2019, to December 29, 2021, with the follow-up performed until July 9, 2023.

Patients received either

• Sugemalimab (1200 mg intravenously, q3w) and CAPOX (capecitabine and oxaliplatin) for up to 6 cycles, then sugemalimab maintenance for up to 24 months (n=241), or

• Placebo and CAPOX on the same regimen (n=238).

The overall survival (OS) and investigator-assessed progression-free survival (PFS) were the primary endpoints. The secondary endpoints were objective response rate (ORR), duration of response (DOR), and safety.

Key Findings

• The overall survival (OS) was significantly better in the group receiving sugemalimab (15.6 months, 95% CI: 13.3-17.8) than the placebo group (12.6 months, 95% CI: 10.6-14.1) with a hazard ratio (HR) of 0.75 (95% CI: 0.61-0.92, p=0.006).

• The progression-free survival (PFS) at the median was 7.6 months (95% CI: 6.4-7.9) in the sugemalimab arm and 6.1 months (95% CI: 5.1-6.4) in the placebo arm (HR: 0.66, 95% CI: 0.54-0.81, p<0.001).

• Objective response rate (ORR) was greater in the sugemalimab group (48.1%) than in the placebo group (38.7%).

• The disease control rate (DCR) was 82.2% with sugemalimab and 74.4% with placebo.

• Grade 3 or worse treatment-related adverse events (TRAEs) occurred in 53.9% of patients treated with sugemalimab and 50.6% of those treated with placebo.

The safety profile of sugemalimab with CAPOX was in line with previous research on anti-PD-L1 treatments. The most frequent grade 3 or better adverse events were:

• Neutropenia (15.3% in the sugemalimab arm vs 13.8% in the placebo arm).

• Anemia (9.8% vs 8.4%).

• Thrombocytopenia (7.2% vs 6.5%).

• Elevated alanine aminotransferase (ALT) levels (5.3% vs 4.9%).

• Severe adverse events were reported in 31.2% of sugemalimab-treated patients and 28.4% of placebo-treated patients.

The study authors concluded that the addition of sugemalimab to chemotherapy extended overall survival and progression-free survival significantly in patients with PD-L1 CPS ≥5 gastroesophageal junction or gastric adenocarcinoma. The safety profile of combination therapy was manageable, further substantiating its potential for use as a first-line therapeutic option. Such evidence justifies the inclusion of sugemalimab in guidelines, bringing about a new expectation for advanced gastric cancer patients.

Reference:

Zhang X, Wang J, Wang G, et al. First-Line Sugemalimab Plus Chemotherapy for Advanced Gastric Cancer: The GEMSTONE-303 Randomized Clinical Trial. JAMA. Published online February 24, 2025. doi:10.1001/jama.2024.28463