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 curve_0-21 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.

Keywords: Advanced solid tumors; Combination anti-TIGIT and anti-PD-L1 cancer immunotherapy; Ethnic sensitivity and population bridging; Immune check point inhibitors; Phase I clinical trials.

Fig. 1

Plot of Cycle 1 serum tiragolumab concentrations (µg/mL; mean ± SD). ^aGlobal GO30103 study, phase Ib tiragolumab 600 mg Q3W plus atezolizumab 1200 mg Q3W cohort. Q3W every 3 weeks, SD standard deviation

Fig. 2

Boxplot of Cycles 1–7 serum tiragolumab and atezolizumab concentrations (µg/mL). ^aGlobal GO30103 study, phase 1b tiragolumab 600 mg Q3W plus atezolizumab 1200 mg Q3W cohort; ^bAtezolizumab PK data have been pooled from all patients in GO30103 who had serum atezolizumab concentration levels after administration of tiragolumab 2–1200 mg Q3W in combination with atezolizumab 1200 mg Q3W. C_max maximum serum concentration, C_min minimal serum concentration, PK pharmacokinetics, Q3W every 3 weeks