PMID- 28494535
OWN - NLM
STAT- MEDLINE
DCOM- 20180904
LR  - 20240324
IS  - 2005-9256 (Electronic)
IS  - 1598-2998 (Print)
IS  - 1598-2998 (Linking)
VI  - 50
IP  - 2
DP  - 2018 Apr
TI  - TAK-264 (MLN0264) in Previously Treated Asian Patients with Advanced 
      Gastrointestinal Carcinoma Expressing Guanylyl Cyclase C: Results from an 
      Open-Label, Non-randomized Phase 1 Study.
PG  - 398-404
LID - 10.4143/crt.2017.074 [doi]
AB  - PURPOSE: This phase 1 dose-escalation portion of the study evaluated the safety, 
      pharmacokinetics (PK), and antitumor activity of TAK-264 in Asian patients with 
      advanced gastrointestinal (GI) carcinoma or metastatic or recurrent gastric or 
      gastroesophageal junction adenocarcinoma expressing guanylyl cyclase C (GCC). 
      MATERIALS AND METHODS: Adult patients with advanced GI malignancies expressing 
      GCC (H-score >/= 10) received TAK-264 on day 1 of 3-week cycles as 30-minute 
      intravenous infusions for up to 1 year or until disease progression or 
      unacceptable toxicity. The primary objectives were to evaluate the safety profile 
      including dose-limiting toxicities (DLTs) during cycle 1, determine the maximum 
      tolerated dose (MTD), and characterize the PK profile of TAK-264. RESULTS: Twelve 
      patients were enrolled and treated with 1.2 mg/kg (n=3), 1.5 mg/kg (n=3), or 1.8 
      mg/kg TAK-264 (n=6). Median number of treatment cycles received was two (range, 1 
      to 10). None of the patients experienced a DLT and the MTD was not determined. 
      Ten patients (83%) experienced adverse events (AEs). The most common were 
      neutropenia, anorexia, and nausea (each reported by four patients). Five patients 
      (42%) experienced grade >/= 3 AEs consisting of tumor hemorrhage and hypertension, 
      ascites, adrenal insufficiency, neutropenia and asthenia. Serum exposure to 
      TAK-264 increased proportionally with the dose and the median half-life was 
      approximately 5.5-6.6 days. No patients experienced an objective response. 
      CONCLUSION: TAK-264 demonstrated a manageable safety profile with limited 
      antitumor activity consistent with studies conducted in Western patients with 
      advanced GI malignancies. TAK-264 exposure increased proportionally with the 
      dose.
FAU - Bang, Yung-Jue
AU  - Bang YJ
AD  - Department of Internal Medicine, Seoul National University College of Medicine, 
      Seoul, Korea.
FAU - Takano, Toshimi
AU  - Takano T
AD  - Department of Medical Oncology, Toranomon Hospital, Tokyo, Japan.
FAU - Lin, Chia-Chi
AU  - Lin CC
AD  - Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
FAU - Fasanmade, Adedigbo
AU  - Fasanmade A
AD  - Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda 
      Pharmaceutical Company Limited, Cambridge, MA, USA.
FAU - Yang, Huyuan
AU  - Yang H
AD  - Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda 
      Pharmaceutical Company Limited, Cambridge, MA, USA.
FAU - Danaee, Hadi
AU  - Danaee H
AD  - Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda 
      Pharmaceutical Company Limited, Cambridge, MA, USA.
FAU - Asato, Takayuki
AU  - Asato T
AD  - Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda 
      Pharmaceutical Company Limited, Cambridge, MA, USA.
FAU - Kalebic, Thea
AU  - Kalebic T
AD  - Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda 
      Pharmaceutical Company Limited, Cambridge, MA, USA.
FAU - Wang, Hui
AU  - Wang H
AD  - Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda 
      Pharmaceutical Company Limited, Cambridge, MA, USA.
FAU - Doi, Toshihiko
AU  - Doi T
AD  - Department of Experimental Therapeutics, National Cancer Center Hospital East, 
      Chiba, Japan.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
DEP - 20170510
PL  - Korea (South)
TA  - Cancer Res Treat
JT  - Cancer research and treatment
JID - 101155137
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 731FA8A8YO (indusatumab)
RN  - EC 4.6.1.2 (Receptors, Enterotoxin)
SB  - IM
MH  - Aged
MH  - Antibodies, Monoclonal/pharmacology/*therapeutic use
MH  - Antibodies, Monoclonal, Humanized
MH  - Female
MH  - Gastrointestinal Neoplasms/*drug therapy/genetics/metabolism
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Receptors, Enterotoxin/*metabolism
PMC - PMC5912138
OTO - NOTNLM
OT  - Clinical trial
OT  - Gastrointestinal cancer
OT  - Stomach
COIS- Yung-Jue Bang, Chia-Chi Lin, Toshimi Takano, and Toshihiko Doi disclose no 
      conflicts of interest. Adedigbo Fasanmade, Huyuan Yang, Hadi Danaee, Takayuki 
      Asato, Thea Kalebic, and Hui Wang are employees of Takeda Pharmaceuticals. 
      Takayuki Asato holds stocks or shares in Takeda Pharmaceutical Company Limited 
      and Chugai Pharmaceutical Company Limited. Thea Kalebic holds stocks in Takeda 
      Pharmaceutical Company Limited. This study was funded by Millennium 
      Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company 
      Limited.
EDAT- 2017/05/13 06:00
MHDA- 2018/09/05 06:00
PMCR- 2018/04/01
CRDT- 2017/05/12 06:00
PHST- 2017/02/13 00:00 [received]
PHST- 2017/05/01 00:00 [accepted]
PHST- 2017/05/13 06:00 [pubmed]
PHST- 2018/09/05 06:00 [medline]
PHST- 2017/05/12 06:00 [entrez]
PHST- 2018/04/01 00:00 [pmc-release]
AID - crt.2017.074 [pii]
AID - crt-2017-074 [pii]
AID - 10.4143/crt.2017.074 [doi]
PST - ppublish
SO  - Cancer Res Treat. 2018 Apr;50(2):398-404. doi: 10.4143/crt.2017.074. Epub 2017 
      May 10.