Phase I study on neoadjuvant combination immunotherapy with mogamulizumab and nivolumab for solid tumors

Jinushi, Koichi; Saito, Takuro; Kurose, Koji; Suzuki, Susumu; Kojima, Takashi; Takahara, Taishi; Makino, Tomoki; Ogawa, Tetsuya; Nishikawa, Hiroyoshi; Kakimi, Kazuhiro; Iida, Shinsuke; Nakajima, Jun; Doki, Yuichiro; Oka, Mikio; Ueda, Ryuzo; Wada, Hisashi

doi:https://doi.org/10.1136/jitc-2024-010634

Phase I study on neoadjuvant combination immunotherapy with mogamulizumab and nivolumab for solid tumors

Jinushi, Koichi; Saito, Takuro; Kurose, Koji et al.

Journal for ImmunoTherapy of Cancer, 2025, 13(4), e010634

アクセス数:25件（2025-12-05 16:41 集計）

固定URL: https://hdl.handle.net/11094/102898

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タイトル	Phase I study on neoadjuvant combination immunotherapy with mogamulizumab and nivolumab for solid tumors
著者	著者名 Jinushi, Koichi
	NRID 1000020646468 1000020646468 ORCID 0000-0002-1733-5064 0000-0002-1733-5064 researchmap permalink tsaito19 tsaito19 Scopus Author ID 57211629912 57211629912 著者名 Saito, Takuro
	NRID 1000030551139 1000030551139 著者名 Kurose, Koji
	NRID 1000070518422 1000070518422 著者名 Suzuki, Susumu
	著者名 Kojima, Takashi
	NRID 1000050790317 1000050790317 著者名 Takahara, Taishi
	NRID 1000080528620 1000080528620 researchmap permalink _-_-_- _-_-_- Scopus Author ID 56339970700 56339970700 著者名 Makino, Tomoki
	NRID 1000040334940 1000040334940 著者名 Ogawa, Tetsuya
	NRID 1000010444431 1000010444431 著者名 Nishikawa, Hiroyoshi
	NRID 1000080273358 1000080273358 著者名 Kakimi, Kazuhiro
	NRID 1000050295614 1000050295614 著者名 Iida, Shinsuke
	NRID 1000090188954 1000090188954 著者名 Nakajima, Jun
	NRID 1000020291445 1000020291445 researchmap permalink ydoki3251 ydoki3251 Scopus Author ID 7006390687 7006390687 著者名 Doki, Yuichiro
	NRID 1000040223995 1000040223995 著者名 Oka, Mikio
	NRID 1000020142169 1000020142169 著者名 Ueda, Ryuzo
	NRID 1000070243459 1000070243459 著者名 Wada, Hisashi
キーワード等	Antibody
	Immunotherapy
	Solid tumor
	T regulatory cell - Treg
内容	Jinushi K., Saito T., Kurose K., et al. Phase I study on neoadjuvant combination immunotherapy with mogamulizumab and nivolumab for solid tumors. Journal for ImmunoTherapy of Cancer 13, e010634 (2025); https://doi.org/10.1136/jitc-2024-010634.
抄録	Background Effector regulatory T cells expressing C-C chemokine receptor 4 (CCR4) suppress antitumor immune responses. We conducted a phase I clinical trial to evaluate the safety and efficacy of preoperative combination therapy with mogamulizumab (an anti-CCR4 antibody) and nivolumab (an anti-programmed death-1 antibody) in patients with solid tumors. Methods Patients with operable solid tumors were enrolled in a 3+3 design, with preoperative nivolumab (3.0 mg/kg) administered intravenously every 2 weeks three times and mogamulizumab at 0.1 mg/kg (cohort 1), 0.3 mg/kg (cohort 2), or 1.0 mg/kg (cohort 3) every week four times. The primary endpoints were safety and the effects of depleting Forkhead box P3⁺ (FoxP3⁺) T cells in the tumor. Results 16 patients were enrolled between June 2016 and April 2020, including those with renal (n=7), lung (n=5), esophageal (n=3), and oral (n=1) cancers. Grade 3-4 treatment-related adverse events were observed in 6 of 16 patients, with lymphopenia (25%) and maculopapular rash (13%) being the most frequent. Grade 5 interstitial pneumonia was observed in one patient; however, the cause of death was disease progression. There were three partial responses (PRs) (one lung and two esophageal cancers) among clinical responses and one complete response (one lung cancer) and nine PRs (five kidney, two lung, and two esophageal cancers) among pathological responses. CCR4⁺FoxP3⁺ T cells were depleted in the tumors of all patients and increases in lymphocytes in tumor tissue according to the tumor immune microenvironment classification were observed in 50% of the patients, which correlated with a better prognosis. Conclusions The preoperative combination of mogamulizumab and nivolumab was safely managed, exerted antitumor effects, and may be an effective option in the preoperative setting. Trial registration number The present study was registered with ClinicalTrials.gov as NCT02946671 (registration date 2016-10-05).
出版者	BMJ Publishing Group
収録物名	Journal for ImmunoTherapy of Cancer
巻(号)	13(4)
ページ	e010634
刊行年月	2025-04-02
言語	英語
ハンドルURL	https://hdl.handle.net/11094/102898
eISSN	20511426
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1136/jitc-2024-010634
アクセス権	open access
権利情報	This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCMI資源タイプ	text
DCTERMS.bibliographicCitation	Journal for ImmunoTherapy of Cancer. 2025, 13(4), p. e010634
DC.title	Phase I study on neoadjuvant combination immunotherapy with mogamulizumab and nivolumab for solid tumors
DC.creator	Jinushi, Koichi
	Saito, Takuro
	Kurose, Koji
	Suzuki, Susumu
	Kojima, Takashi
	Takahara, Taishi
	Makino, Tomoki
	Ogawa, Tetsuya
	Nishikawa, Hiroyoshi
	Kakimi, Kazuhiro
	Iida, Shinsuke
	Nakajima, Jun
	Doki, Yuichiro
	Oka, Mikio
	Ueda, Ryuzo
	Wada, Hisashi
DC.publisher	BMJ Publishing Group
DC.language' scheme='DCTERMS.RFC1766	英語
DC.type' scheme='DCTERMS.DCMIType	text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-04-02
DC.identifier	https://doi.org/10.1136/jitc-2024-010634
DC.subject	Antibody
	Immunotherapy
	Solid tumor
	T regulatory cell - Treg
DC.description	Jinushi K., Saito T., Kurose K., et al. Phase I study on neoadjuvant combination immunotherapy with mogamulizumab and nivolumab for solid tumors. Journal for ImmunoTherapy of Cancer 13, e010634 (2025); https://doi.org/10.1136/jitc-2024-010634.
DCTERMS.abstract	Background Effector regulatory T cells expressing C-C chemokine receptor 4 (CCR4) suppress antitumor immune responses. We conducted a phase I clinical trial to evaluate the safety and efficacy of preoperative combination therapy with mogamulizumab (an anti-CCR4 antibody) and nivolumab (an anti-programmed death-1 antibody) in patients with solid tumors. Methods Patients with operable solid tumors were enrolled in a 3+3 design, with preoperative nivolumab (3.0 mg/kg) administered intravenously every 2 weeks three times and mogamulizumab at 0.1 mg/kg (cohort 1), 0.3 mg/kg (cohort 2), or 1.0 mg/kg (cohort 3) every week four times. The primary endpoints were safety and the effects of depleting Forkhead box P3⁺ (FoxP3⁺) T cells in the tumor. Results 16 patients were enrolled between June 2016 and April 2020, including those with renal (n=7), lung (n=5), esophageal (n=3), and oral (n=1) cancers. Grade 3-4 treatment-related adverse events were observed in 6 of 16 patients, with lymphopenia (25%) and maculopapular rash (13%) being the most frequent. Grade 5 interstitial pneumonia was observed in one patient; however, the cause of death was disease progression. There were three partial responses (PRs) (one lung and two esophageal cancers) among clinical responses and one complete response (one lung cancer) and nine PRs (five kidney, two lung, and two esophageal cancers) among pathological responses. CCR4⁺FoxP3⁺ T cells were depleted in the tumors of all patients and increases in lymphocytes in tumor tissue according to the tumor immune microenvironment classification were observed in 50% of the patients, which correlated with a better prognosis. Conclusions The preoperative combination of mogamulizumab and nivolumab was safely managed, exerted antitumor effects, and may be an effective option in the preoperative setting. Trial registration number The present study was registered with ClinicalTrials.gov as NCT02946671 (registration date 2016-10-05).
DC.rights	This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
DC.format	102898
citation_title	Phase I study on neoadjuvant combination immunotherapy with mogamulizumab and nivolumab for solid tumors
citation_author	Jinushi, Koichi
	Saito, Takuro
	Kurose, Koji
	Suzuki, Susumu
	Kojima, Takashi
	Takahara, Taishi
	Makino, Tomoki
	Ogawa, Tetsuya
	Nishikawa, Hiroyoshi
	Kakimi, Kazuhiro
	Iida, Shinsuke
	Nakajima, Jun
	Doki, Yuichiro
	Oka, Mikio
	Ueda, Ryuzo
	Wada, Hisashi
citation_publisher	BMJ Publishing Group
citation_language	英語
citation_date	2025-04-02
citation_journal_title	Journal for ImmunoTherapy of Cancer
citation_volume	13
citation_issue	4
citation_firstpage	e010634
citation_doi	https://doi.org/10.1136/jitc-2024-010634
citation_public_url	https://hdl.handle.net/11094/102898

Phase I study on neoadjuvant combination immunotherapy with mogamulizumab and nivolumab for solid tumors

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