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

Number of Access:25（2025-12-05 17:33 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/102898

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Title	Phase I study on neoadjuvant combination immunotherapy with mogamulizumab and nivolumab for solid tumors
Creator	CreatorName Jinushi, Koichi
	NRID 1000020646468 1000020646468 ORCID 0000-0002-1733-5064 0000-0002-1733-5064 researchmap permalink tsaito19 tsaito19 Scopus Author ID 57211629912 57211629912 CreatorName Saito, Takuro
	NRID 1000030551139 1000030551139 CreatorName Kurose, Koji
	NRID 1000070518422 1000070518422 CreatorName Suzuki, Susumu
	CreatorName Kojima, Takashi
	NRID 1000050790317 1000050790317 CreatorName Takahara, Taishi
	NRID 1000080528620 1000080528620 researchmap permalink _-_-_- _-_-_- Scopus Author ID 56339970700 56339970700 CreatorName Makino, Tomoki
	NRID 1000040334940 1000040334940 CreatorName Ogawa, Tetsuya
	NRID 1000010444431 1000010444431 CreatorName Nishikawa, Hiroyoshi
	NRID 1000080273358 1000080273358 CreatorName Kakimi, Kazuhiro
	NRID 1000050295614 1000050295614 CreatorName Iida, Shinsuke
	NRID 1000090188954 1000090188954 CreatorName Nakajima, Jun
	NRID 1000020291445 1000020291445 researchmap permalink ydoki3251 ydoki3251 Scopus Author ID 7006390687 7006390687 CreatorName Doki, Yuichiro
	NRID 1000040223995 1000040223995 CreatorName Oka, Mikio
	NRID 1000020142169 1000020142169 CreatorName Ueda, Ryuzo
	NRID 1000070243459 1000070243459 CreatorName Wada, Hisashi
Subject	Antibody
	Immunotherapy
	Solid tumor
	T regulatory cell - Treg
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.
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).
Publisher	BMJ Publishing Group
Source Title	Journal for ImmunoTherapy of Cancer
Volume (Issue)	13(4)
Page	e010634
Date of Issued	2025-04-02
Language	English
Handle URL	https://hdl.handle.net/11094/102898
eISSN	20511426
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1136/jitc-2024-010634
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	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	English
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	English
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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