PMID- 33528890
OWN - NLM
STAT- MEDLINE
DCOM- 20210830
LR  - 20210830
IS  - 2523-3548 (Electronic)
IS  - 2523-3548 (Linking)
VI  - 41
IP  - 2
DP  - 2021 Feb
TI  - Safety, tolerability, and pharmacokinetics of BAT8001 in patients with 
      HER2-positive breast cancer: An open-label, dose-escalation, phase I study.
PG  - 171-182
LID - 10.1002/cac2.12135 [doi]
AB  - BACKGROUND: The introductions of anti- human epidermal growth factor receptor-2 
      (HER2) agents have significantly improved the treatment outcome of patients with 
      HER2-positive breast cancer. BAT8001 is a novel antibody-drug conjugate targeting 
      human epidermal growth factor receptor-2 (HER2)-expressing cells composed of a 
      trastuzumab biosimilar linked to the drug-linker Batansine. This dose-escalation, 
      phase I study was designed to assess the safety, tolerability, pharmacokinetics, 
      and preliminary anti-tumor activity of BAT8001 in patients with HER2-positive 
      locally advanced or metastatic breast cancer. METHODS: This trial was conducted 
      in subjects with histologically confirmed HER2-positive breast cancer (having 
      evaluable lesions and an Eastern Cooperative Oncology Group performance status of 
      0 or 1) using a 3 + 3 design of escalating BAT8001 doses. Patients received 
      BAT8001 intravenously in a 21-day cycle, with dose escalation in 5 cohorts: 1.2, 
      2.4, 3.6, 4.8, and 6.0 mg/kg. The primary objective was to evaluate the safety 
      and tolerability of BAT8001. Preliminary activity of BAT8001 was also assessed as 
      a secondary objective. RESULTS: Between March 2017 to May 2018, 29 HER2-positive 
      breast cancer patients were enrolled. The observed dose-limiting toxicities were 
      grade 4 thrombocytopenia and grade 3 elevated transaminase. The maximum tolerated 
      dose was determined to be 3.6 mg/kg. Grade 3 or greater adverse events (AEs) 
      occurred in 14 (48.3%) of 29 patients, including thrombocytopenia in 12 (41.4%) 
      patients, aspartate aminotransferase increased in 4 (13.8%) patients, gamma-glutamyl 
      transferase increased in 2 (6.9%) patients, alanine aminotransferase increased in 
      2 (6.9%) patients, diarrhea in 2 (6.9%) patients. Objective response was observed 
      in 12 (41.4%; 95% confidence interval [CI] = 23.5%-61.1%) and disease control 
      (including patients achieving objective response and stable disease) was observed 
      in 24 (82.8%; 95% CI = 64.2%-94.2%) patients. CONCLUSIONS: BAT8001 demonstrated 
      favorable safety profiles, with promising anti-tumor activity in patients with 
      HER2-positive locally advanced or metastatic breast cancer. BAT8001 has the 
      potential to provide a new therapeutic option in patients with metastatic 
      HER2-positive breast cancer.
CI  - (c) 2021 The Authors. Cancer Communications published by John Wiley & Sons 
      Australia, Ltd. on behalf of Sun Yat-sen University Cancer Center.
FAU - Hong, Ruoxi
AU  - Hong R
AD  - Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key 
      Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer 
      Medicine, Guangzhou, Guangdong, 510060, P. R. China.
FAU - Xia, Wen
AU  - Xia W
AD  - Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key 
      Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer 
      Medicine, Guangzhou, Guangdong, 510060, P. R. China.
FAU - Wang, Liye
AU  - Wang L
AUID- ORCID: 0000-0001-9219-8162
AD  - Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key 
      Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer 
      Medicine, Guangzhou, Guangdong, 510060, P. R. China.
FAU - Lee, Kaping
AU  - Lee K
AD  - Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key 
      Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer 
      Medicine, Guangzhou, Guangdong, 510060, P. R. China.
FAU - Lu, Qianyi
AU  - Lu Q
AD  - Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key 
      Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer 
      Medicine, Guangzhou, Guangdong, 510060, P. R. China.
FAU - Jiang, Kuikui
AU  - Jiang K
AD  - Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key 
      Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer 
      Medicine, Guangzhou, Guangdong, 510060, P. R. China.
FAU - Li, Shengfeng
AU  - Li S
AD  - Biology Research Department, Bio-Thera Solutions, Ltd., Guangzhou, Guangdong, 
      510060, P. R. China.
FAU - Yu, Jinquan
AU  - Yu J
AD  - Biology Research Department, Bio-Thera Solutions, Ltd., Guangzhou, Guangdong, 
      510060, P. R. China.
FAU - Wei, Jin
AU  - Wei J
AD  - Clinical Development Department, Bio-Thera Solutions, Ltd., Guangzhou, Guangdong, 
      510060, P. R. China.
FAU - Tang, Weijia
AU  - Tang W
AD  - Biology Research Department, Bio-Thera Solutions, Ltd., Guangzhou, Guangdong, 
      510060, P. R. China.
FAU - Zhou, Danyang
AU  - Zhou D
AD  - Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key 
      Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer 
      Medicine, Guangzhou, Guangdong, 510060, P. R. China.
FAU - An, Xin
AU  - An X
AD  - Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key 
      Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer 
      Medicine, Guangzhou, Guangdong, 510060, P. R. China.
FAU - Huang, Jiajia
AU  - Huang J
AD  - Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key 
      Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer 
      Medicine, Guangzhou, Guangdong, 510060, P. R. China.
FAU - Xue, Cong
AU  - Xue C
AD  - Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key 
      Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer 
      Medicine, Guangzhou, Guangdong, 510060, P. R. China.
FAU - Bi, Xiwen
AU  - Bi X
AD  - Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key 
      Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer 
      Medicine, Guangzhou, Guangdong, 510060, P. R. China.
FAU - Shi, Yanxia
AU  - Shi Y
AUID- ORCID: 0000-0002-5414-8049
AD  - Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key 
      Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer 
      Medicine, Guangzhou, Guangdong, 510060, P. R. China.
FAU - Yuan, Zhongyu
AU  - Yuan Z
AD  - Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key 
      Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer 
      Medicine, Guangzhou, Guangdong, 510060, P. R. China.
FAU - Xu, Fei
AU  - Xu F
AD  - Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key 
      Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer 
      Medicine, Guangzhou, Guangdong, 510060, P. R. China.
FAU - Wang, Shusen
AU  - Wang S
AUID- ORCID: 0000-0003-0139-5780
AD  - Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key 
      Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer 
      Medicine, Guangzhou, Guangdong, 510060, P. R. China.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210202
PL  - United States
TA  - Cancer Commun (Lond)
JT  - Cancer communications (London, England)
JID - 101723675
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Immunoconjugates)
RN  - P188ANX8CK (Trastuzumab)
SB  - IM
MH  - Antibodies, Monoclonal, Humanized/therapeutic use
MH  - *Breast Neoplasms/drug therapy
MH  - Female
MH  - Humans
MH  - *Immunoconjugates
MH  - Maximum Tolerated Dose
MH  - Trastuzumab/therapeutic use
PMC - PMC7896747
OTO - NOTNLM
OT  - BAT8001
OT  - HER2-postive
OT  - antibody-drug conjugate
OT  - breast cancer
OT  - dose escalation
OT  - maximum tolerated dose
COIS- SW received research grants from Pfizer for work outside the submitted work.
EDAT- 2021/02/03 06:00
MHDA- 2021/08/31 06:00
PMCR- 2021/02/02
CRDT- 2021/02/02 12:17
PHST- 2020/08/22 00:00 [received]
PHST- 2020/11/05 00:00 [revised]
PHST- 2021/01/05 00:00 [accepted]
PHST- 2021/02/03 06:00 [pubmed]
PHST- 2021/08/31 06:00 [medline]
PHST- 2021/02/02 12:17 [entrez]
PHST- 2021/02/02 00:00 [pmc-release]
AID - CAC212135 [pii]
AID - 10.1002/cac2.12135 [doi]
PST - ppublish
SO  - Cancer Commun (Lond). 2021 Feb;41(2):171-182. doi: 10.1002/cac2.12135. Epub 2021 
      Feb 2.