Phase I study of the anti-TIGIT antibody tiragolumab in combination with atezolizumab in Japanese patients with advanced or metastatic solid tumors

• Published in: Cancer chemotherapy and pharmacology Vol. 94; no. 1; pp. 109 - 115
• Main Authors: Yamamoto, Noboru, Koyama, Takafumi, Sato, Jun, Yoshida, Tatsuya, Sudo, Kazuki, Iwasa, Satoru, Kondo, Shunsuke, Yonemori, Kan, Kawasaki, Atsuko, Satake, Kyoko, Shibata, Shoyo, Shimizu, Toshio
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.07.2024; Springer Nature B.V
• Subjects: Adult; Aged; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - pharmacokinetics; Antibodies, Monoclonal, Humanized - therapeutic use; Anticancer properties; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - pharmacokinetics; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Antitumor agents; Apoptosis; Cancer Research; Cell death; Cholangiocarcinoma; Clinical outcomes; Clinical trials; East Asian People; Female; Humans; Immune checkpoint; Immunoglobulins; Immunoreceptor tyrosine-based inhibition motif; Japan; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Lymphocytes T; Male; Medicine; Medicine & Public Health; Metastases; Metastasis; Middle Aged; Monoclonal antibodies; Neoplasms - drug therapy; Neoplasms - pathology; Non-small cell lung carcinoma; Oncology; Pancreatic cancer; Parameter modification; Patients; Pharmacokinetics; Pharmacology/Toxicology; Short Communication; Small cell lung carcinoma; Solid tumors; Toxicity; Tumors; Japan; Tiragolumab; Phase I study; Japanese patients; Solid tumors; TIGIT; Atezolizumab
• ISSN: 0344-5704; 1432-0843; 1432-0843
• DOI: 10.1007/s00280-023-04627-3

Purpose Tiragolumab is a monoclonal antibody that binds to the inhibitory immune checkpoint TIGIT (T-cell immunoreceptor with Ig and ITIM domains). In early phase clinical trials, tiragolumab in combination with the programmed death-ligand 1-inhibitor atezolizumab was well tolerated and has demonstrated preliminary anti-tumor activity in patients with advanced/metastatic solid tumors. We report the results of a phase I study of tiragolumab plus atezolizumab in Japanese patients (jRCT2080224926). Methods Japanese patients ≥ 20 years old received tiragolumab (600 mg) and atezolizumab (1200 mg) intravenously every 21 days until unacceptable toxicity or disease progression. Primary endpoints were safety and pharmacokinetic (PK) parameters of tiragolumab plus atezolizumab. Secondary endpoints were anti-tumor activity. Results Three patients were enrolled with diagnoses of non-small cell lung cancer, pancreatic cancer, and cholangiocarcinoma. No dose-limiting toxicities were observed. Two patients experienced treatment-related adverse events (AEs) of any grade. There were no grade ≥ 3 AEs, serious AEs, AEs leading to discontinuation, modification or withdrawal of any study drug, or AEs leading to death. At cycle 1, mean PK parameters of tiragolumab were as follows: C max 217 μg/mL; C min 54.9 μg/mL; area under the concentration–time curve from 0 to the last measurable concentration, 2000 μg·day/mL; t 1/2 , 17.6 days. Best overall response was stable disease in two patients. Conclusion Tiragolumab plus atezolizumab was well tolerated in Japanese patients with advanced/metastatic solid tumors, and no differences in tiragolumab PK characteristics were noted between Japanese patients enrolled in this study, and non-Japanese patients enrolled in a global phase Ia/Ib study. These results may support the inclusion of Japanese patients in ongoing global phase III clinical trials. Trial registration number jRCT2080224926.