PMID- 35773363
OWN - NLM
STAT- MEDLINE
DCOM- 20220704
LR  - 20220906
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 12
IP  - 1
DP  - 2022 Jun 30
TI  - A phase 1b study of andecaliximab in combination with S-1 plus platinum in 
      Japanese patients with gastric adenocarcinoma.
PG  - 11007
LID - 10.1038/s41598-022-13801-1 [doi]
LID - 11007
AB  - Andecaliximab (ADX) is a monoclonal antibody that inhibits matrix 
      metalloproteinase 9 (MMP9), an extracellular enzyme involved in matrix 
      remodeling, tumor growth, and metastasis. In preclinical models, MMP9 inhibitors 
      have been shown to enhance the cytotoxic effects of chemotherapeutic agents and 
      to suppress distant metastasis. In this phase Ib, multicenter study, the safety 
      and efficacy of ADX combined with S-1 plus cisplatin (SP) or S-1 plus oxaliplatin 
      (SOX) as a first-line treatment were evaluated in Japanese patients with advanced 
      gastric or gastroesophageal junction (GEJ) adenocarcinoma. ADX was administrated 
      at a dose of 800 mg every 2 weeks for the SP cohort and 1200 mg every three weeks 
      for the SOX cohort. As of December 2019, 16 patients were enrolled (six patients 
      in the SP cohort and 10 patients in the SOX cohort). Peripheral sensory 
      neuropathy (69%), anorexia (63%), nausea (56%), and decreased neutrophil counts 
      (44%) were the most common adverse events (AEs). The grade 3 or higher AEs 
      attributed to ADX were stomatitis and abnormal hepatic function (each one 
      patient) in the SP cohort and decreased neutrophil counts (two patients) in the 
      SOX cohort. The objective response rate in 11 patients with measurable target 
      lesions was 73% (8/11), based on the investigator's evaluation. Median 
      progression-free survival was11.9 months (90% confidence interval, 5.6-16.6), and 
      median overall survival was not reached. In conclusion, ADX combined with S-1 
      plus platinum demonstrated a manageable safety profile and promising clinical 
      activity in the first-line treatment of patients with advanced gastric or GEJ 
      adenocarcinoma.Clinical Trial Registration information: ClinicalTrials.gov 
      Identifier: NCT02862535 (11/08/2016) and protocol ID: GS-US-296-1884.
CI  - (c) 2022. The Author(s).
FAU - Ooki, Akira
AU  - Ooki A
AD  - Department of Gastroenterological Chemotherapy, Cancer Institute Hospital of 
      Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, 
      Japan.
FAU - Satoh, Taroh
AU  - Satoh T
AD  - Palliative and Supportive Care Center, Osaka University Hospital, Osaka, Japan.
FAU - Muro, Kei
AU  - Muro K
AD  - Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
FAU - Takashima, Atsuo
AU  - Takashima A
AD  - Division of Gastrointestinal Medical Oncology, National Cancer Center Hospital, 
      Tokyo, Japan.
FAU - Kadowaki, Shigenori
AU  - Kadowaki S
AD  - Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
FAU - Sakai, Daisuke
AU  - Sakai D
AD  - Palliative and Supportive Care Center, Osaka University Hospital, Osaka, Japan.
FAU - Ichimura, Takashi
AU  - Ichimura T
AD  - Department of Gastroenterological Chemotherapy, Cancer Institute Hospital of 
      Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, 
      Japan.
FAU - Mitani, Seiichiro
AU  - Mitani S
AD  - Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
FAU - Kudo, Toshihiro
AU  - Kudo T
AD  - Department of Medical Oncology, Osaka International Cancer Institute, Osaka, 
      Japan.
FAU - Chin, Keisho
AU  - Chin K
AD  - Department of Gastroenterological Chemotherapy, Cancer Institute Hospital of 
      Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, 
      Japan.
FAU - Kitano, Shigehisa
AU  - Kitano S
AD  - Department of Experimental Therapeutics, National Cancer Center Hospital, Tokyo, 
      Japan.
FAU - Thai, Dung
AU  - Thai D
AD  - Gilead Sciences, Inc., Foster City, CA, USA.
FAU - Zavodovskaya, Marianna
AU  - Zavodovskaya M
AD  - Gilead Sciences, Inc., Foster City, CA, USA.
FAU - Liu, JieJane
AU  - Liu J
AD  - Gilead Sciences, Inc., Foster City, CA, USA.
FAU - Boku, Narikazu
AU  - Boku N
AD  - Division of Gastrointestinal Medical Oncology, National Cancer Center Hospital, 
      Tokyo, Japan.
FAU - Yamaguchi, Kensei
AU  - Yamaguchi K
AD  - Department of Gastroenterological Chemotherapy, Cancer Institute Hospital of 
      Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, 
      Japan. kensei.yamaguchi@jfcr.or.jp.
LA  - eng
SI  - ClinicalTrials.gov/NCT02862535
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20220630
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Drug Combinations)
RN  - 0 (S-1 plus cisplatin)
RN  - 04ZR38536J (Oxaliplatin)
RN  - 49DFR088MY (Platinum)
RN  - 571045EIM4 (andecaliximab)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - Q20Q21Q62J (Cisplatin)
RN  - Adenocarcinoma Of Esophagus
SB  - IM
MH  - *Adenocarcinoma/pathology
MH  - Antibodies, Monoclonal, Humanized
MH  - *Antineoplastic Agents/pharmacology
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects
MH  - Cisplatin
MH  - Drug Combinations
MH  - Esophageal Neoplasms
MH  - Esophagogastric Junction/pathology
MH  - Humans
MH  - Japan
MH  - Matrix Metalloproteinase 9/therapeutic use
MH  - Oxaliplatin/pharmacology
MH  - Platinum/therapeutic use
MH  - *Stomach Neoplasms/pathology
PMC - PMC9246925
COIS- KY received speaker honoraria from Chugai Pharmaceutical Co. Ltd., Bristol-Myers 
      Squibb, Merck Serono, Taiho Pharmaceutical Co., Takeda, and Eli Lilly; a 
      consultant fee from Takeda Pharmaceutical Co. Ltd.; honoraria from Tsumura Co. 
      Ltd., Nihon Kayaku Co. Ltd., and Chugai Pharmaceutical Co. Ltd; research grants 
      from Sumitomo Dainippon Pharma, Gilead Sciences, MSD, and Boehringer Ingelheim, 
      Daiichi Sankyo, and Chugai Pharmaceutical Co. Ltd; Speaker honoraria, research 
      grants, and scholarship grant from Ono Pharmaceutical, Yakult Honsha Co., Ltd., 
      and Sanofi. AO received speaker honoraria from Merck Serono, Chugai, Takeda 
      Pharmaceutical Co. Ltd., Taiho Pharmaceutical Co., Bristol Myers-Squib, Daiichi 
      Sankyo, and Ono Pharmaceutical. TS belonged to Endosed Department of Yakult 
      Honsha Co., Ltd., Chugai Pharmaceutical Co., Ltd., and Ono pharmaceutical Co., 
      Ltd.received speaker honoraria from Chugai Pharmaceutical Co. Ltd.Daiichi Sankyo 
      Ono Pharmaceutical. Bristol-Myers Squibb, Merck Serono and Elli Lilly, a 
      consultant fee from Takara Bio. TK research fund from Chugai Pharmaceutical Co. 
      Ltd. Daiichi Sankyo Ono Pharmaceutical. Bristol-Myers Squibb, Parexell, Hutchmed, 
      Giliad, BeiGene and Elli Lilly. NB has received research grant from Ono 
      pharmaceutical company and Takeda pharmaceutical company, and honorarium from Ono 
      pharmaceutical company, Taiho, ONO Pharmaceutical. Co. Ltd and Bristol Myers 
      Squibb. KM received grants (to his institution and himself) from Astellas, Amgen, 
      Daiichi Sankyo, Merck Sharp & Dohme Corp., Merck Serono, Ono Pharmaceutical Co., 
      Ltd, Parexel International, Pfizer, Sanofi, Solasia Pharma, and Taiho 
      Pharmaceutical Co; consulting fees from Amgen, AstraZeneca, and Ono 
      Pharmaceutical Co., Ltd; honoraria from Bayer, Bristol-Myers Squibb, Chugai, Eli 
      Lilly, Ono Pharmaceutical Co., Ltd, Sanofi, Taiho Pharmaceutical Co, and Takeda. 
      SK received honoraria for lectures from Eli Lilly, Taiho Pharmaceutical Co., ONO 
      Pharmaceutical. Co. Ltd, Bristol Myers-Squib, Chugai Pharmaceutical Co. Ltd, 
      Bayer, Merck Serono, Eisai, and Daiichi-Sankyo; departmental research grants from 
      Taiho Pharmaceutical Co., Eli Lilly, MSD, Chugai Pharmaceutical Co. Ltd, 
      Nobelpharma, Daiichi Sankyo, ONO Pharmaceutical. Co. Ltd, and Yansen. AT received 
      personal fees from Eli Lilly, Taiho Pharmaceutical, Chugai Pharma, and Merck 
      Serono; grants from Merck Sharp & Dohme, Eisai, Bayer Yakuhin, Bristol-Myers 
      Squibb, and BeiGene Japan; grants and personal fees from Ono Pharmaceutical and 
      Takeda. TK belonged to a donated fund laboratory of Yakult Honsha Co., Ltd., 
      Chugai Pharmaceutical Co., Ltd., and Ono pharmaceutical Co., Ltd. SM received 
      speaker honoraria from Taiho Pharmaceutical Co., Takeda Pharmaceutical Co., and 
      Ono Pharmaceutical Co, and grants from Taiho Pharmaceutical Co. SK received 
      personal fees from Astra Zeneca, Pfizer, Taiho, Novartis, Sumitomo Dainippon 
      Pharma, Bristol-Myers Squibb, AYUMI Pharmaceutical Corporation, Rakuten Medical, 
      GSK, ImmuniT Research Inc., and PMDA(Pharmaceuticals and Medical Devices Agency) 
      outside the submitted work; grants and personal fees from Gilead Sciences, 
      Chugai, Boehringer Ingelheim, MSD, Eisai, Ono Pharmaceutical Co., Ltd, REGENERON, 
      and Daiichi Sankyo; grants from Astellas, PACT Pharma, Takara Bio Inc., grants 
      from AMED (Japan Agency for Medical Research and Development), and JSPS (Japan 
      Society for the Promotion of Science).
EDAT- 2022/07/01 06:00
MHDA- 2022/07/06 06:00
PMCR- 2022/06/30
CRDT- 2022/06/30 23:23
PHST- 2021/10/16 00:00 [received]
PHST- 2022/05/27 00:00 [accepted]
PHST- 2022/06/30 23:23 [entrez]
PHST- 2022/07/01 06:00 [pubmed]
PHST- 2022/07/06 06:00 [medline]
PHST- 2022/06/30 00:00 [pmc-release]
AID - 10.1038/s41598-022-13801-1 [pii]
AID - 13801 [pii]
AID - 10.1038/s41598-022-13801-1 [doi]
PST - epublish
SO  - Sci Rep. 2022 Jun 30;12(1):11007. doi: 10.1038/s41598-022-13801-1.