Nivolumab plus anlotinib hydrochloride in advanced gastric adenocarcinoma and esophageal squamous cell carcinoma: the phase II OASIS trial

Abstract

Vascular endothelial growth factor inhibitors, including tyrosine kinase inhibitors (TKIs), possess immunomodulatory properties and have shown promising outcomes when combined with anti-PD-1 antibodies. The OASIS phase II trial (NCT04503967) is designed to determine the clinical activity and safety of nivolumab (anti-PD-1) and anlotinib hydrochloride (a multi-targets TKI) as second-line or above therapy in patients with advanced gastric adenocarcinoma (GAC) and esophageal squamous cell carcinoma (ESCC). From December 2020 to September 2022, 45 patients with GAC and 3 with ESCC were enrolled in this study. The pre-specified endpoints were reached, with the primary endpoint of overall response rate achieving 29.2%. For secondary objectives, disease control rate was 64.6%; median progression-free survival was 4.0 months; and median overall survival was 11.1 months with a manageable toxicity profile. The exploratory analyses unveiled that the balance of gut bacteria and the presence of a pre-existing immune signature characterized by a high percentage of CD68 ⁺PD-L1 ⁺ PD-1 ⁺ macrophages and low pretreatment variant allele frequencies (VAF), as well as low expression of certain cytokines were significantly associated with improved clinical outcomes in patients with GAC.

Abstract

Anlotinib hydrochloride is a multi-target tyrosine kinase receptor inhibitor, previously combined with anti-PD1 as therapeutic strategy for several cancer types. Here the authors report the results of a phase II trial of nivolumab (anti-PD1) plus anlotinib hydrochloride in patients with advanced gastric adenocarcinoma and esophageal squamous cell carcinoma.