Benmelstobart plus anlotinib and chemotherapy in HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma: A phase 2 study

This phase 2 study investigates first-line benmelstobart plus anlotinib and chemotherapy in human epidermal growth factor receptor 2 (HER2)-negative unresectable locally advanced/metastatic gastric or gastroesophageal junction (G/GEJ) cancer. Twenty-five eligible patients receive benmelstobart plus anlotinib and chemotherapy for 6 cycles, followed by benmelstobart and anlotinib maintenance. Of 24 patients with post-treatment imaging, objective response rate (ORR) is 75.0% (95% confidence interval [CI], 53.3%-90.2%; partial response [PR], 18 [75.0%]), and disease control rate (DCR) is 100.0%. The median duration of response (DoR) is 10.9 months. By the date cutoff, the median follow-up is 15.8 months. Median progression-free survival (PFS) and overall survival (OS) among all 25 patients are 10.3 and 18.2 months, respectively. Survival outcomes are not associated with programmed death-ligand 1 (PD-L1) expression. Lymphocytes, T cells, and CD3⁺CD8⁺ T cells are enriched in patients with long-term response (PFS > 12 months). Most common grade ≥3 treatment-related adverse event (TRAE) is neutrophil count decreased (12%). This study shows promising efficacy and safety, representing a potential first-line option in patients with HER2-negative advanced G/GEJ cancer, regardless of PD-L1 expressions. The study was registered at ClinicalTrials.gov (NCT04891900).