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Developmental therapeutics

1573 - Anti-CC-chemokine receptor 4 (CCR4) antibody mogamulizumab (Moga) and nivolumab (Nivo) combination phase I study in patients with advanced or metastatic solid tumors


10 Sep 2017


Developmental therapeutics


Noboru Yamamoto


Annals of Oncology (2017) 28 (suppl_5): v605-v649. 10.1093/annonc/mdx440


N. Yamamoto1, K. Muro2, H. Ishii3, T. Kato4, T. Tsushima5, M. Takenoyama6, S. Oizumi7, T. Kawakami8, T. Doi9

Author affiliations

  • 1 Department Of Experimental Therapeutics, National Cancer Center Hospital, 104-0045 - Tokyo/JP
  • 2 Department Of Clinical Oncology And Outpatient Treatment Center, Aichi Cancer Center Hospital, 464-8681 - Aichi/JP
  • 3 Clinical Research Center, National Hospital Organization Shikoku Cancer Center, 791-0280 - Ehime/JP
  • 4 Division Of Thoracic Oncology, Kanagawa Cancer Center, 241-8515 - Kanagawa/JP
  • 5 Divison Of Gi Oncology, Shizuoka Cancer Center, 411-877 - Shizuoka/JP
  • 6 Department Of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center, 811-1395 - Fukuoka/JP
  • 7 Department Of Respiratory Medicine, National Hospital Organization Hokkaido Cancer Center, 003-0804 - Hokkaido/JP
  • 8 Clinical Development Center, Kyowa Hakko Kirin Co., Ltd., 100-004 - Tokyo/JP
  • 9 Department Of Experimental Therapeutics, National Cancer Center Hospital East, 277-8577 - Chiba/JP


Abstract 1573


Regulatory T cells (Tregs) are known to inhibit immune responses against tumors, and express CCR4 which makes them a potential therapeutic target. Mogamulizumab, a humanized IgG1 monoclonal antibody targeting CCR4, has been approved for CCR4+ T cell lymphomas in Japan and can deplete effector Tregs. Nivolumab, anti-PD-1 immune checkpoint inhibitor, has shown promising activity in patients (pts) with various solid tumors. Moga and Nivo combination therapy is possible to block multiple mechanisms involved in suppression of antitumor immunity and results in enhanced antitumor immune responses compared with either of the agents alone. This is the first report of preliminary results using this combination.


This study is composed of a dose escalation part (DEP) and an expansion part (EXP). Pts with advanced or metastatic solid tumor received Nivo 3 mg/kg every 2 weeks + Moga 0.3-1 mg/kg once a week for 4 weeks and subsequently every 2 weeks until disease progression/toxicity. The objectives were to assess safety primarily, antitumor effect (RECIST 1.1) and pharmacokinetics (PK) secondarily, and biomarkers exploratorily.


Six and 90 pts were enrolled to DEP and EXP, respectively, as of June/1/2017. No dose limiting toxicities were observed in DEP. Drug-related adverse events (AEs) of grade 3-4 occurred in 26.0% in DEP and EXP. No grade 5 drug-related AE was observed. The most frequently observed drug-related AEs were rash (38.5%), rash maculo-papular (22.9%), stomatitis (13.5%) and diarrhoea (13.5%). Some confirmed objective responses were observed in pts with several types of tumor such as hepatocellular carcinoma (4/15, 26.7%). Furthermore, out of 15 pts with pancreatic adenocarcinoma, 1 confirmed PR and 5 SD (including 2 unconfirmed PR) were observed.


Moga and Nivo combination therapy showed acceptable safety profile and encouraging antitumor activity in several advanced or metastatic solid tumors. The combination of anti-PD-1 with anti-CCR4 that controls Tregs is a possible new strategy in cancer immunity. Additional data including the efficacy of other tumor types, PK and biomarker will be reported. Further study of this combination is warranted.

Clinical trial identification

The protocol number is “0761-013” (NCT02476123).

Legal entity responsible for the study

Ono Pharmaceutical Co. Ltd and Kyowa Hakko Kirin Co., Ltd


Ono Pharmaceutical Co. Ltd and Kyowa Hakko Kirin Co., Ltd


N. Yamamoto: Corporate-sponsored research: Astellas, Bayer, BMS, Chugai, Daiichi Sankyo, Eisai, Kyowa Kirin, Boehringer Ingelheim, Novartis, Ono, Pfizer, Takeda, Taiho, Quintiles, Membership on an advisory board: Eisai, Takeda, OncoTherapy Science. K. Muro: Corporate-sponsored research: Shionogi, MSD, Daiichi Sankyo, Kyowa Kirin, Gilead Sciences, Honoraria: Chugai, Takeda, Eli Lilly, Merck Serono, Taiho, Yakult. H. Ishii: Consultant: Ono, Corporate-sponsored research: Taiho, Honoraria: Taiho, Nobelpharma, Yakult, Mochida, Eisai, Kyowa Kirin, Eli Lilly. T. Kato: Corporate-sponsored research/Honoraria:Chugai, AstraZeneca, Boehringer Ingelheim, Eli Lilly, MSD, Ono, Donation/contribution:Boehringer Ingelheim, Corporate-sponsored research:Taiho, Abbvie, Pfizer, BMS, Kyowa Kirin, Merck Serono. M. Takenoyama: Corporate-sponsored research: BMS, Chugai, Eli Lilly, Kyowa Kirin, Boehringer Ingelheim, Novartis, Ono, Honoraria: AstraZeneca, BMS, Chugai, Eli Lilly, Kyowa Kirin, Ono, Taiho. S. Oizumi: Honoraria: AstraZeneca. T. Kawakami: Employee of Kyowa Kirin. T. Doi: Consultant/advisor and Research: Eli Lilly, Novartis, MSD, Chugai, Kyowa Kirin, Boehringer Ingelheim, Daiichi Sankyo, Consultant/advisor: Amgen, Research: Pfizer, Taiho, Merck Serono, Astellas, Janssen, Takeda, Sumitomo, Bayer, Celgene. All other authors have declared no conflicts of interest.

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