Phase I pharmacokinetic, safety, and preliminary efficacy study of tiragolumab in combination with atezolizumab in Chinese patients with advanced solid tumors

Abstract

Purpose Tiragolumab is an immunoglobulin G1 monoclonal antibody targeting the immune checkpoint T cell immunoreceptor with immunoglobulin and immunoreceptor ITIM domains. Targeting multiple immune pathways may improve anti-tumor responses. The phase I YP42514 study assessed the pharmacokinetics (PK), safety, and preliminary efficacy of tiragolumab plus atezolizumab in Chinese patients with advanced solid tumors. Methods Adult patients from mainland China with Eastern Cooperative Oncology Group performance score 0/1, life expectancy of ≥ 12 weeks, and adequate hematologic/end organ function were eligible. Patients received tiragolumab 600 mg and atezolizumab 1200 mg intravenous every 3 weeks. Key endpoints were PK (serum concentrations of tiragolumab and atezolizumab) and safety. Results from this study were compared with the global phase I study, GO30103 (NCT02794571). Results In this study, 20 patients received a median of five doses of tiragolumab plus atezolizumab. Median age was 57.5 years, 85.0% of patients were male and the most common tumor type was non-small cell lung cancer. Exposures in Chinese patients were comparable to the global GO30103 population: geometric mean ratio was 1.07 for Cycle 1 tiragolumab area under the concentration–time curve0–21 and 0.92 and 0.93 for Cycle 1 peak and trough atezolizumab exposure, respectively. Treatment-related adverse events were consistent across the Chinese and global populations. Two patients (10.0%) in this study achieved a partial response. Conclusion In this study, tiragolumab plus atezolizumab was tolerable and demonstrated preliminary anti-tumor activity. There were no meaningful differences in the PK or safety of tiragolumab plus atezolizumab between the Chinese and global populations. Clinical trial registration number: China Clinical Trial Registry Identifier CTR20210219/YP42514. Date of registration 16 March 2021.

Efficacy and Safety of Atezolizumab as a PD-L1 Inhibitor in the Treatment of Cervical Cancer: A Systematic Review

“…Recent phase I studies have highlighted the evolving landscape of combination immunotherapies in the treatment of advanced solid tumors, specifically emphasizing the role of novel checkpoint inhibitors alongside established therapies. The YP42514 study [ 43 ] assessed tiragolumab combined with atezolizumab, revealing that this regimen was generally well tolerated with a manageable safety profile, achieving partial responses in 10% of the Chinese cohort with advanced solid tumors, predominantly non-small cell lung cancer. Similarly, the GO30103 trial [ 44 ] evaluated tiragolumab’s safety and preliminary efficacy, identifying a recommended phase 2 dosage and demonstrating encouraging antitumor activity, particularly in immunotherapy-naive patients with non-small cell lung cancer and esophageal cancer, achieving objective response rates of 46% and 28%, respectively.…”