PMID- 38206370
OWN - NLM
STAT- Publisher
LR  - 20240331
IS  - 1432-0843 (Electronic)
IS  - 0344-5704 (Linking)
DP  - 2024 Jan 11
TI  - Phase I study of the anti-TIGIT antibody tiragolumab in combination with 
      atezolizumab in Japanese patients with advanced or metastatic solid tumors.
LID - 10.1007/s00280-023-04627-3 [doi]
AB  - 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 mug/mL; C(min) 54.9 mug/mL; 
      area under the concentration-time curve from 0 to the last measurable 
      concentration, 2000 mug.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.
CI  - (c) 2024. The Author(s).
FAU - Yamamoto, Noboru
AU  - Yamamoto N
AUID- ORCID: 0000-0002-0787-2851
AD  - Department of Experimental Therapeutics, National Cancer Center Hospital, Tsukiji 
      5-1-1, Chuo-Ku, Tokyo, 104-0045, Japan. nbryamam@ncc.go.jp.
FAU - Koyama, Takafumi
AU  - Koyama T
AD  - Department of Experimental Therapeutics, National Cancer Center Hospital, Tsukiji 
      5-1-1, Chuo-Ku, Tokyo, 104-0045, Japan.
FAU - Sato, Jun
AU  - Sato J
AD  - Department of Experimental Therapeutics, National Cancer Center Hospital, Tsukiji 
      5-1-1, Chuo-Ku, Tokyo, 104-0045, Japan.
FAU - Yoshida, Tatsuya
AU  - Yoshida T
AD  - Department of Experimental Therapeutics, National Cancer Center Hospital, Tsukiji 
      5-1-1, Chuo-Ku, Tokyo, 104-0045, Japan.
FAU - Sudo, Kazuki
AU  - Sudo K
AD  - Department of Experimental Therapeutics, National Cancer Center Hospital, Tsukiji 
      5-1-1, Chuo-Ku, Tokyo, 104-0045, Japan.
FAU - Iwasa, Satoru
AU  - Iwasa S
AD  - Department of Experimental Therapeutics, National Cancer Center Hospital, Tsukiji 
      5-1-1, Chuo-Ku, Tokyo, 104-0045, Japan.
FAU - Kondo, Shunsuke
AU  - Kondo S
AD  - Department of Experimental Therapeutics, National Cancer Center Hospital, Tsukiji 
      5-1-1, Chuo-Ku, Tokyo, 104-0045, Japan.
FAU - Yonemori, Kan
AU  - Yonemori K
AD  - Department of Experimental Therapeutics, National Cancer Center Hospital, Tsukiji 
      5-1-1, Chuo-Ku, Tokyo, 104-0045, Japan.
FAU - Kawasaki, Atsuko
AU  - Kawasaki A
AD  - Chugai Pharmaceutical Co., Ltd, 1-1 Nihonbashi-Muromachi 2-Chome Chuo-Ku, Tokyo, 
      103-8324, Japan.
FAU - Satake, Kyoko
AU  - Satake K
AD  - Chugai Pharmaceutical Co., Ltd, 1-1 Nihonbashi-Muromachi 2-Chome Chuo-Ku, Tokyo, 
      103-8324, Japan.
FAU - Shibata, Shoyo
AU  - Shibata S
AD  - Chugai Pharmaceutical Co., Ltd, 1-1 Nihonbashi-Muromachi 2-Chome Chuo-Ku, Tokyo, 
      103-8324, Japan.
FAU - Shimizu, Toshio
AU  - Shimizu T
AD  - Department of Experimental Therapeutics, National Cancer Center Hospital, Tsukiji 
      5-1-1, Chuo-Ku, Tokyo, 104-0045, Japan.
LA  - eng
PT  - Journal Article
DEP - 20240111
PL  - Germany
TA  - Cancer Chemother Pharmacol
JT  - Cancer chemotherapy and pharmacology
JID - 7806519
SB  - IM
EIN - Cancer Chemother Pharmacol. 2024 Mar 31;:. PMID: 38556530
OTO - NOTNLM
OT  - Atezolizumab
OT  - Japanese patients
OT  - Phase I study
OT  - Solid tumors
OT  - TIGIT
OT  - Tiragolumab
EDAT- 2024/01/11 12:42
MHDA- 2024/01/11 12:42
CRDT- 2024/01/11 11:06
PHST- 2023/08/24 00:00 [received]
PHST- 2023/11/24 00:00 [accepted]
PHST- 2024/01/11 12:42 [pubmed]
PHST- 2024/01/11 12:42 [medline]
PHST- 2024/01/11 11:06 [entrez]
AID - 10.1007/s00280-023-04627-3 [pii]
AID - 10.1007/s00280-023-04627-3 [doi]
PST - aheadofprint
SO  - Cancer Chemother Pharmacol. 2024 Jan 11. doi: 10.1007/s00280-023-04627-3.