Journal Article
. 2021 Dec; 83(4):827-840.
doi: 10.18999/nagjms.83.4.827.

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

Takuro Saito 1 Koji Kurose 2 Takashi Kojima 3 Takeru Funakoshi 4 Eiichi Sato 5 Hiroyoshi Nishikawa 6 Jun Nakajima 7 Yasuyuki Seto 8 Kazuhiro Kakimi 9 Shinsuke Iida 10 Yuichiro Doki 1 Mikio Oka 11 Ryuzo Ueda 12 Hisashi Wada 13 
  • PMID: 34916725
  •     25 References
  •     1 citations


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.

Keywords: CCR4; clinical trial; mogamulizumab; regulatory T cells; solid cancer patients.

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