Phase I pharmacokinetic, safety, and preliminary efficacy study of tiragolumab in combination with atezolizumab in Chinese patients with advanced solid tumors.
| Title: | Phase I pharmacokinetic, safety, and preliminary efficacy study of tiragolumab in combination with atezolizumab in Chinese patients with advanced solid tumors. |
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| Authors: | Shemesh CS; Clinical Pharmacology, Genentech Inc., South San Francisco, CA, USA. shemesh.colby@gene.com.; Wang Y; Clinical Trial Center, West China Hospital, Sichuan University, Chengdu, China.; An A; Safety Science, F. Hoffmann-La Roche Ltd, Beijing, China.; Ding H; Clinical Pharmacology, Genentech Inc., South San Francisco, CA, USA.; Chan P; Clinical Pharmacology, Genentech Inc., South San Francisco, CA, USA.; Liu Q; Clinical Pharmacology, Genentech Inc., South San Francisco, CA, USA.; Chen YW; Bioanalytical Science, Genentech Inc., South San Francisco, CA, USA.; Wu B; Clinical Pharmacology, Genentech Inc., South San Francisco, CA, USA.; Wu Q; Product Development Oncology, F. Hoffmann-La Roche Ltd, Shanghai, China.; Wang X; Sir Run Run Shaw Hospital Zhejiang University School of Medicine, Hangzhou, China. |
| Source: | Cancer chemotherapy and pharmacology [Cancer Chemother Pharmacol] 2024 Jul; Vol. 94 (1), pp. 45-55. Date of Electronic Publication: 2024 Mar 07. |
| Publication Type: | Journal Article; Clinical Trial, Phase I |
| Language: | English |
| Journal Info: | Publisher: Springer Verlag Country of Publication: Germany NLM ID: 7806519 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-0843 (Electronic) Linking ISSN: 03445704 NLM ISO Abbreviation: Cancer Chemother Pharmacol Subsets: MEDLINE |
| Imprint Name(s): | Publication: Berlin : Springer Verlag; Original Publication: Berlin, New York, Springer International. |
| MeSH Terms: | Antibodies, Monoclonal, Humanized*/adverse effects ; Antibodies, Monoclonal, Humanized*/pharmacokinetics ; Antibodies, Monoclonal, Humanized*/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols*/adverse effects ; Antineoplastic Combined Chemotherapy Protocols*/pharmacokinetics ; Antineoplastic Combined Chemotherapy Protocols*/therapeutic use ; Neoplasms*/drug therapy ; Neoplasms*/pathology; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; China ; East Asian People |
| 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.; (© 2024. The Author(s).) |
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| Contributed Indexing: | 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 |
| Molecular Sequence: | ClinicalTrials.gov NCT02794571 |
| Substance Nomenclature: | 0 (Antibodies, Monoclonal, Humanized); 52CMI0WC3Y (atezolizumab) |
| Entry Date(s): | Date Created: 20240307 Date Completed: 20240718 Latest Revision: 20240723 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC11258083 |
| DOI: | 10.1007/s00280-024-04650-y |
| PMID: | 38451273 |
| Database: | MEDLINE |
Journal Article; Clinical Trial, Phase I