PMID- 38515348
OWN - NLM
STAT- MEDLINE
DCOM- 20240325
LR  - 20240417
IS  - 1752-8062 (Electronic)
IS  - 1752-8054 (Print)
IS  - 1752-8054 (Linking)
VI  - 17
IP  - 3
DP  - 2024 Mar
TI  - Clinical dose rationale of tislelizumab in patients with solid or hematological 
      advanced tumors.
PG  - e13769
LID - 10.1111/cts.13769 [doi]
LID - e13769
AB  - Tislelizumab, an anti-programmed cell death protein 1 monoclonal antibody, has 
      demonstrated improved survival benefits over standard of care for multiple cancer 
      indications. We present the clinical rationale and data supporting tislelizumab 
      dose recommendation in patients with advanced tumors. The phase I, 
      first-in-human, dose-finding BGB-A317-001 study (data cutoff [DCO]: August 2017) 
      examined the following tislelizumab dosing regimens: 0.5-10 mg/kg every 2 weeks 
      (q2w), 2-5 mg/kg q2w or q3w, and 200 mg q3w. Similar objective response rates 
      (ORRs) were reported in the 2 and 5 mg/kg q2w or q3w cohorts. Safety outcomes 
      (grade >/=3 adverse events [AEs], AEs leading to dose modification/discontinuation, 
      immune-mediated AEs, and infusion-related reactions) were generally comparable 
      across the dosing range examined. These results, alongside the convenience of a 
      fixed q3w dose, formed the basis of choosing 200 mg q3w as the recommended dosing 
      regimen for further clinical use. Pooled exposure-response (E-R) analyses by 
      logistic regression using data from study BGB-A317-001 (DCO: August 2020) and 
      three additional phase I/II studies (DCOs: 2018-2020) showed no statistically 
      significant correlation between tislelizumab pharmacokinetic exposure and ORR 
      across multiple solid tumor types or classical Hodgkin's lymphoma, nor was 
      exposure associated with any of the safety end points evaluated over the dose 
      range tested. Hence, tislelizumab showed a relatively flat E-R relationship. 
      Overall, the totality of data, including efficacy, safety, and E-R analyses, 
      together with the relative convenience of a fixed q3w dose, provided clinical 
      rationale for the recommended dosing regimen of tislelizumab 200 mg q3w for 
      multiple cancer indications.
CI  - (c) 2024 The Authors. Clinical and Translational Science published by Wiley 
      Periodicals LLC on behalf of American Society for Clinical Pharmacology and 
      Therapeutics.
FAU - Yu, Tian
AU  - Yu T
AUID- ORCID: 0000-0002-4044-7902
AD  - BeiGene USA, Inc., San Mateo, California, USA.
FAU - Liu, Xiangyu
AU  - Liu X
AUID- ORCID: 0000-0002-7102-4988
AD  - BeiGene USA, Inc., San Mateo, California, USA.
FAU - Wu, Chi-Yuan
AU  - Wu CY
AUID- ORCID: 0009-0008-2157-6195
AD  - BeiGene USA, Inc., San Mateo, California, USA.
FAU - Tang, Zhiyu
AU  - Tang Z
AUID- ORCID: 0009-0004-4734-7586
AD  - BeiGene USA, Inc., San Mateo, California, USA.
FAU - Wang, Hongwei
AU  - Wang H
AUID- ORCID: 0009-0007-3175-0276
AD  - BeiGene USA, Inc., Cambridge, Massachusetts, USA.
FAU - Schnell, Patrick
AU  - Schnell P
AUID- ORCID: 0009-0001-8483-9764
AD  - BeiGene USA, Inc., Ridgefield Park, New Jersey, USA.
FAU - Wan, Ya
AU  - Wan Y
AUID- ORCID: 0009-0000-9139-1825
AD  - BeiGene (Shanghai) Co., Ltd., Shanghai, China.
FAU - Wang, Kun
AU  - Wang K
AUID- ORCID: 0000-0003-2609-6058
AD  - Shanghai Qiangshi Information Technology Co., Ltd., Shanghai, China.
FAU - Liu, Lucy
AU  - Liu L
AUID- ORCID: 0000-0002-4219-3897
AD  - Shanghai Qiangshi Information Technology Co., Ltd., Shanghai, China.
FAU - Gao, Yuying
AU  - Gao Y
AUID- ORCID: 0009-0009-0208-3210
AD  - Shanghai Qiangshi Information Technology Co., Ltd., Shanghai, China.
FAU - Sahasranaman, Srikumar
AU  - Sahasranaman S
AUID- ORCID: 0000-0002-0762-2967
AD  - BeiGene USA, Inc., San Mateo, California, USA.
FAU - Budha, Nageshwar
AU  - Budha N
AUID- ORCID: 0009-0005-3373-657X
AD  - BeiGene USA, Inc., San Mateo, California, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Transl Sci
JT  - Clinical and translational science
JID - 101474067
RN  - 0KVO411B3N (tislelizumab)
RN  - 0 (Antibodies, Monoclonal, Humanized)
SB  - IM
MH  - Humans
MH  - Antibodies, Monoclonal, Humanized/pharmacokinetics
MH  - *Neoplasms/pathology
MH  - *Hematologic Neoplasms
MH  - *Drug-Related Side Effects and Adverse Reactions
PMC - PMC10958174
COIS- T.Y., X.L., Z.T., H.W., P.S., and N.B. are employees of BeiGene USA, Inc. and own 
      stock in BeiGene. C.-Y.W. and S.S. are former employees of BeiGene USA, Inc. Y.W. 
      is an employee of BeiGene (Shanghai) Co., Ltd. and owns stock in BeiGene. K.W., 
      L.L., and Y.G. are employees of Shanghai Qiangshi Information Technology Co., 
      Ltd.
EDAT- 2024/03/22 06:44
MHDA- 2024/03/25 06:42
PMCR- 2024/03/22
CRDT- 2024/03/22 03:23
PHST- 2024/02/12 00:00 [revised]
PHST- 2023/09/29 00:00 [received]
PHST- 2024/02/21 00:00 [accepted]
PHST- 2024/03/25 06:42 [medline]
PHST- 2024/03/22 06:44 [pubmed]
PHST- 2024/03/22 03:23 [entrez]
PHST- 2024/03/22 00:00 [pmc-release]
AID - CTS13769 [pii]
AID - 10.1111/cts.13769 [doi]
PST - ppublish
SO  - Clin Transl Sci. 2024 Mar;17(3):e13769. doi: 10.1111/cts.13769.