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Phase Ib study on the humanized anti-CCR4 antibody, KW-0761, in advanced solid tumors.


ABSTRACT: 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.

SUBMITTER: Saito T 

PROVIDER: S-EPMC8648528 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Phase Ib study on the humanized anti-CCR4 antibody, KW-0761, in advanced solid tumors.

Saito Takuro T   Kurose Koji K   Kojima Takashi T   Funakoshi Takeru T   Sato Eiichi E   Nishikawa Hiroyoshi H   Nakajima Jun J   Seto Yasuyuki Y   Kakimi Kazuhiro K   Iida Shinsuke S   Doki Yuichiro Y   Oka Mikio M   Ueda Ryuzo R   Wada Hisashi H  

Nagoya journal of medical science 20211101 4


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 re  ...[more]

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2019-08-06 | GSE120028 | GEO