PMID- 34916725 OWN - NLM STAT- MEDLINE DCOM- 20220207 LR - 20220207 IS - 2186-3326 (Electronic) IS - 0027-7622 (Print) IS - 0027-7622 (Linking) VI - 83 IP - 4 DP - 2021 Nov TI - Phase Ib study on the humanized anti-CCR4 antibody, KW-0761, in advanced solid tumors. PG - 827-840 LID - 10.18999/nagjms.83.4.827 [doi] AB - Tregs infiltrate tumors and inhibit antitumor immunity. KW-0761 (Mogamulizumab) is a humanized anti-CCR4 monoclonal antibody that could eliminate activated Tregs with high immunosuppressive activity that express CCR4. In this phase Ib trial, KW-0761 was used as a cancer immunotherapeutic reagent to deplete Tregs in patients with advanced or recurrent solid CCR4-negative tumors. Thirty-nine patients with solid cancer were treated with KW-0761 at a dose of 0.1 or 1.0 mg/kg. The safety, clinical responses, and effects of Treg depletion were analyzed. Any grade and grade 3-4 treatment-related adverse events (AEs) were observed in 36 (92%) and 14 (36%) out of 39 patients, respectively. All treatment-related AEs were manageable. One and 5 patients achieved a partial response and stable disease, respectively, during treatment and were long survivors. The efficient depletion of Treg in peripheral blood was confirmed in both cohorts. Therefore, the administration of KW-0761 was safe, resulting in the depletion of Tregs in peripheral blood and potential immune responses in patients with solid cancer. The combined use of KW-0761 to deplete Tregs and other immunotherapies is a promising approach to augment immune responses. FAU - Saito, Takuro AU - Saito T AD - Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan. FAU - Kurose, Koji AU - Kurose K AD - Department of Respiratory Medicine, Kawasaki Medical School, Kurashiki, Japan. FAU - Kojima, Takashi AU - Kojima T AD - Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan. FAU - Funakoshi, Takeru AU - Funakoshi T AD - Department of Dermatology, Keio University School of Medicine, Tokyo, Japan. FAU - Sato, Eiichi AU - Sato E AD - Department of Pathology, Institute of Medical Science (Medical Research Center), Tokyo Medical University, Tokyo, Japan. FAU - Nishikawa, Hiroyoshi AU - Nishikawa H AD - Division of Cancer Immunology, Research Institute/Exploratory Oncology Research & Clinical Trial Center (EPOC), National Cancer Center, Tokyo/Kashiwa, Japan. AD - Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan. FAU - Nakajima, Jun AU - Nakajima J AD - Department of Thoracic Surgery, University of Tokyo Graduate School of Medicine, Tokyo, Japan. FAU - Seto, Yasuyuki AU - Seto Y AD - Department of Gastrointestinal Surgery, University of Tokyo Graduate School of Medicine, Tokyo, Japan. FAU - Kakimi, Kazuhiro AU - Kakimi K AD - Department of Immunotherapeutics, The University of Tokyo Hospital, Tokyo, Japan. FAU - Iida, Shinsuke AU - Iida S AD - Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. FAU - Doki, Yuichiro AU - Doki Y AD - Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan. FAU - Oka, Mikio AU - Oka M AD - Department of Immuno-Oncology, Kawasaki Medical School, Kurashiki, Japan. FAU - Ueda, Ryuzo AU - Ueda R AD - Department of Tumor Immunology, Aichi Medical University School of Medicine, Nagakute, Japan. FAU - Wada, Hisashi AU - Wada H AD - Department of Clinical Research in Tumor Immunology, Osaka University Graduate School of Medicine, Suita, Japan. LA - eng PT - Clinical Trial, Phase I PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PL - Japan TA - Nagoya J Med Sci JT - Nagoya journal of medical science JID - 0412011 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Antineoplastic Agents) RN - 0 (CCR4 protein, human) RN - 0 (Receptors, CCR4) RN - YI437801BE (mogamulizumab) SB - IM MH - Antibodies, Monoclonal, Humanized/*therapeutic use MH - Antineoplastic Agents/*therapeutic use MH - Humans MH - Neoplasms/*drug therapy/immunology MH - Receptors, CCR4/*antagonists & inhibitors/immunology MH - Treatment Outcome PMC - PMC8648528 OTO - NOTNLM OT - CCR4 OT - clinical trial OT - mogamulizumab OT - regulatory T cells OT - solid cancer patients COIS- T.K. received honoraria and research funding from Ono Pharmaceutical, MSD, Shionogi, Bristol-Myers Squibb, Chugai Pharmaceutical, Amgen, Astellas Pharmaceutical, Oncolys BioPharma, Parexel, and Merck Serono outside of this study. T.F. received research funding from Ono Pharmaceutical outside of this study. H.N. received honoraria and research funding from Ono Pharmaceutical, Chugai Pharmaceutical, MSD, and Bristol-Myers Squibb, and research funding from Taiho Pharmaceutical, Daiichi-Sankyo, Kyowa Kirin, Zenyaku Kogyo, Oncolys BioPharma, Debiopharma, Asahi-Kasei, Sysmex, Fujifilm, SRL, Astellas Pharmaceutical, Sumitomo Dainippon Pharma, and BD Japan outside of this study. K.K. received research funding from TAKARA BIO and MSD outside of this study. The Department of Immunotherapeutics, The University of Tokyo Hospital is endowed by TAKARA BIO. S.I. received honoraria and research funding from Ono Pharmaceutical, Takeda, Sanofi, Bristol-Myers Squibb, Janssen, Celgene and Daichi-Sankyo, and research funding from Kyowa Kirin, Abbvie, Chugai Pharmaceutical, MSD, and Gilead outside of this study. Y.D. received honoraria and research funding from Ono Pharmaceutical, Taiho Pharmaceutical, and research funding from Chugai Pharmaceutical, Covidien Japan, Johnson & Johnson, and honoraria from Otsuka Pharmaceutical outside of this study. M.O. received research funding from Thyas, Sysmex, and Pole Star outside of this study. R.U. received research funding from Ono Pharmaceutical, Chugai Pharmaceutical, and Kyowa Kirin outside of this study. H.W. received research funding from Ono Pharmaceutical and Kyowa Kirin, and honoraria from Ono Pharmaceutical, Chugai Pharmaceutical, MSD, and Bristol-Myers Squibb outside of this study. The Department of Clinical Research in Tumor Immunology, Osaka University Graduate School of Medicine is a joint research laboratory with Shionogi & Co., Ltd. EDAT- 2021/12/18 06:00 MHDA- 2022/02/08 06:00 PMCR- 2021/11/01 CRDT- 2021/12/17 06:49 PHST- 2021/07/02 00:00 [received] PHST- 2021/07/19 00:00 [accepted] PHST- 2021/12/17 06:49 [entrez] PHST- 2021/12/18 06:00 [pubmed] PHST- 2022/02/08 06:00 [medline] PHST- 2021/11/01 00:00 [pmc-release] AID - 10.18999/nagjms.83.4.827 [doi] PST - ppublish SO - Nagoya J Med Sci. 2021 Nov;83(4):827-840. doi: 10.18999/nagjms.83.4.827.