TY - JOUR
T1 - Phase Ib Study On The Humanized Anti-Ccr4 Antibody, Kw-0761, In Advanced Solid Tumors
AU - Saito, Takuro
AU - Kurose, Koji
AU - Kojima, Takashi
AU - Funakoshi, Takeru
AU - Sato, Eiichi
AU - Nishikawa, Hiroyoshi
AU - Nakajima, Jun
AU - Seto, Yasuyuki
AU - Kakimi, Kazuhiro
AU - Iida, Shinsuke
AU - Doki, Yuichiro
AU - Oka, Mikio
AU - Ueda, Ryuzo
AU - Wada, Hisashi
N1 - Funding Information:
This study was supported by Grants-in-Aid for Scientific Research (S) grant no. 17H06162 (H.N.), Challenging Exploratory Research grant no. 16K15551 (H.N.), Research Activity Start-up grant no. 15H06878 (Y.M.), Young Scientists (B) grant no. 17K15738 (Y.M.), and Scientific Research (B) grant no. 19H03729 (H.W.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan; by the Projects for Cancer Research by Therapeutic Evolution [P-CREATE, no. 16cm0106301h0001 (H.N.) and no. 17cm0106322h0002 (Y.M.)], by the Development of Technology for Patient Stratification Biomarker Discovery grant [no.19ae0101074s0401 (R.U. and H.N.)] from the Japan Agency for Medical Research and Development (AMED), and by the National Cancer Center Research and Development Fund [no. 28-A-7 and 31-A-7 (H.N.)].
Funding Information:
We thank all the patients and their families who participated in this clinical trial. We also thank all the nurses, clinical research coordinators in Kawasaki Medical School Hospital, Nagoya City University Hospital, Osaka University Hospital, and National Cancer Center Hospital East, Tokyo University Hospital, Keio University Hospital, review committees, and medical experts who were involved in this study. We are grateful to Drs. Y. Ueda, H. Nagase, Y. Ohue, T. Oguri, A. Arakawa, M. Nakamura, Y. Mori, T. Ishida, H. Matsushita, M. Anraku, and M. Sugaya for their clinical support, Dr. H. Ito for statistical support, and Drs. K. Iwata, S. Kihara, and T. Hida for data and safety monitoring support. We are also grateful to Kyowa Hakko Kirin for providing us with the investigational drug KW-0761.
Publisher Copyright:
© 2021. Nagoya Journal of Medical Science,All Rights Reserved.
PY - 2021
Y1 - 2021
N2 - 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.
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.
KW - CCR4
KW - clinical trial
KW - mogamulizumab
KW - regulatory T cells
KW - solid cancer patients
UR - http://www.scopus.com/inward/record.url?scp=85120950726&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85120950726&partnerID=8YFLogxK
U2 - 10.18999/nagjms.83.4.827
DO - 10.18999/nagjms.83.4.827
M3 - Article
C2 - 34916725
AN - SCOPUS:85120950726
SN - 0027-7622
VL - 83
SP - 827
EP - 840
JO - Nagoya Journal of Medical Science
JF - Nagoya Journal of Medical Science
IS - 4
ER -
