PMID- 36342599
OWN - NLM
STAT- MEDLINE
DCOM- 20221130
LR  - 20230117
IS  - 1437-7772 (Electronic)
IS  - 1341-9625 (Print)
IS  - 1341-9625 (Linking)
VI  - 27
IP  - 12
DP  - 2022 Dec
TI  - Safety, tolerability, pharmacokinetics, and antitumour activity of oleclumab in 
      Japanese patients with advanced solid malignancies: a phase I, open-label study.
PG  - 1795-1804
LID - 10.1007/s10147-022-02242-5 [doi]
AB  - BACKGROUND: Cluster of differentiation (CD) 73-targeted immunotherapy and CD73 
      inhibition may reduce adenosine production, which can augment the host and/or 
      immunotherapy response to tumours. We aimed to assess the safety and 
      tolerability, pharmacokinetics, and antitumour activity of oleclumab, an 
      anti-CD73 monoclonal antibody, in adult Japanese patients with advanced solid 
      malignancies resistant to standard therapy. METHODS: In this phase I, 
      single-centre, open-label study, patients received oleclumab 1500 mg (Cohort 1) 
      or 3000 mg (Cohort 2) intravenously every 2 weeks. RESULTS: In total, six 
      patients were enrolled in the study (three in each cohort), and all six patients 
      received the study treatment. The median patient age was 56.0 years and 4/6 were 
      males. All patients (100%) reported adverse events (AEs) during the study; five 
      (83.3%) patients reported AEs related to the study treatment. One (16.7%) patient 
      reported a Grade 3 AE (neutrophil count decreased) that was not related to the 
      study treatment. No AEs with an outcome of death were reported, and no patients 
      reported AEs or serious AEs leading to oleclumab discontinuation/dose 
      interruption. No dose-limiting toxicities were reported, and no patient 
      discontinued due to an AE related to the study treatment. Oleclumab exposure 
      increased dose proportionally. No patient achieved disease control at 8 weeks, 
      and all six patients developed progressive disease. CONCLUSIONS: Oleclumab was 
      well tolerated in adult Japanese patients with advanced solid malignancies and no 
      unexpected safety concerns were raised; oleclumab exposure increased with dose. 
      Future studies on combination therapy with other agents are warranted.
CI  - (c) 2022. The Author(s).
FAU - Kondo, Shunsuke
AU  - Kondo S
AUID- ORCID: 0000-0001-9565-117X
AD  - National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. 
      shkondo@ncc.go.jp.
FAU - Iwasa, Satoru
AU  - Iwasa S
AD  - National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
FAU - Koyama, Takafumi
AU  - Koyama T
AUID- ORCID: 0000-0001-5807-8458
AD  - National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
FAU - Fujita, Tomoko
AU  - Fujita T
AUID- ORCID: 0000-0002-6629-6380
AD  - AstraZeneca K.K., 3-1, Ofuka-cho, Kita-ku, Osaka, 530-0011, Japan.
FAU - Sugibayashi, Ko
AU  - Sugibayashi K
AUID- ORCID: 0000-0003-0285-8054
AD  - AstraZeneca K.K., 3-1-1, Shibaura, Minato-ku, Tokyo, 108-0023, Japan.
AD  - AstraZeneca, 136 Hills Road, Cambridge, CB2 8PA, UK.
FAU - Murayama, Kosho
AU  - Murayama K
AUID- ORCID: 0000-0003-3301-9966
AD  - AstraZeneca K.K., 3-1, Ofuka-cho, Kita-ku, Osaka, 530-0011, Japan.
FAU - Yamamoto, Noboru
AU  - Yamamoto N
AUID- ORCID: 0000-0002-0787-2851
AD  - National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
DEP - 20221107
PL  - Japan
TA  - Int J Clin Oncol
JT  - International journal of clinical oncology
JID - 9616295
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents)
SB  - IM
MH  - Adult
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Antibodies, Monoclonal/adverse effects
MH  - Antibodies, Monoclonal, Humanized/therapeutic use
MH  - *Antineoplastic Agents/therapeutic use
MH  - Japan
MH  - *Neoplasms/drug therapy/pathology
PMC - PMC9700577
OTO - NOTNLM
OT  - Advanced solid malignancies
OT  - Antitumour activity
OT  - Oleclumab
OT  - Pharmacokinetics
OT  - Phase I
OT  - Safety
COIS- SK has received research funding from Astellas Pharma Inc., AstraZeneca K.K., 
      AbbVie, Eli Lilly and Company, MSD, Boehringer Ingelheim, and Pfizer. SI has no 
      conflicts of interest to disclose. TK has received honoraria from Sysmex 
      Corporation and research funding from PACT Pharma. TF, KS, and KM are employees 
      of AstraZeneca K.K. NY has provided an advisory role for Eisai, Takeda 
      Pharmaceutical Company, Otsuka Pharmaceutical, Boehringer Ingelheim, CMIC, and 
      Chugai Pharmaceutical Co., Ltd.; received research funding from Astellas Pharma 
      Inc., Chugai Pharmaceutical Co., Ltd., Eisai, Taiho Pharmaceutical, Bristol Myers 
      Squibb, Pfizer, Novartis, Eli Lilly, AbbVie, Daiichi Sankyo Co., Ltd., Bayer, 
      Boehringer Ingelheim, Kyowa Kirin Co., Ltd., Takeda Pharmaceutical Company, Ono 
      Pharmaceutical, Janssen Pharma, MSD, Merck, GlaxoSmithKline, Sumitomo Dainippon 
      Pharma, Chiome Bioscience, Otsuka Pharmaceutical, Carna Biosciences, Genmab, and 
      Shionogi; and received honoraria from AstraZeneca K.K., Eli Lilly, Ono 
      Pharmaceutical, Chugai Pharmaceutical Co., Ltd., Sysmex Corporation, Daiichi 
      Sankyo Co., Ltd., and Eisai.
EDAT- 2022/11/08 06:00
MHDA- 2022/11/30 06:00
PMCR- 2022/11/07
CRDT- 2022/11/07 11:17
PHST- 2022/03/08 00:00 [received]
PHST- 2022/08/22 00:00 [accepted]
PHST- 2022/11/08 06:00 [pubmed]
PHST- 2022/11/30 06:00 [medline]
PHST- 2022/11/07 11:17 [entrez]
PHST- 2022/11/07 00:00 [pmc-release]
AID - 10.1007/s10147-022-02242-5 [pii]
AID - 2242 [pii]
AID - 10.1007/s10147-022-02242-5 [doi]
PST - ppublish
SO  - Int J Clin Oncol. 2022 Dec;27(12):1795-1804. doi: 10.1007/s10147-022-02242-5. 
      Epub 2022 Nov 7.