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

IF 10.3 1区医学 Q1 IMMUNOLOGY

Journal for Immunotherapy of Cancer Pub Date : 2025-04-02 DOI:10.1136/jitc-2024-010634

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

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引用次数: 0

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).

查看原文本刊更多论文

mogamulizumab和nivolumab联合免疫治疗实体瘤的I期研究。

背景：表达C-C趋化因子受体4（CCR4）的效应调节性T细胞会抑制抗肿瘤免疫反应。我们开展了一项I期临床试验，评估实体瘤患者术前联合使用mogamulizumab（一种抗CCR4抗体）和nivolumab（一种抗程序性死亡-1抗体）治疗的安全性和有效性：采用3+3设计入组可手术实体瘤患者，术前静脉注射尼妥珠单抗（3.0 mg/kg），每两周一次，共三次；mogamulizumab的剂量为0.1 mg/kg（队列1）、0.3 mg/kg（队列2）或1.0 mg/kg（队列3），每周一次，共四次。主要终点是安全性和消耗肿瘤中叉头盒P3+（FoxP3+）T细胞的效果：16名患者于2016年6月至2020年4月期间入组，包括肾癌（7人）、肺癌（5人）、食管癌（3人）和口腔癌（1人）患者。16例患者中有6例出现3-4级治疗相关不良事件，其中最常见的是淋巴细胞减少（25%）和斑丘疹（13%）。一名患者出现了5级间质性肺炎，但死因是疾病进展。临床反应中有 3 例部分反应（PR）（1 例肺癌和 2 例食管癌），病理反应中有 1 例完全反应（1 例肺癌）和 9 例 PR（5 例肾癌、2 例肺癌和 2 例食管癌）。所有患者肿瘤中的CCR4+FoxP3+ T细胞均被清除，根据肿瘤免疫微环境分类，50%的患者肿瘤组织中淋巴细胞增加，这与较好的预后有关：结论：术前联合使用mogamulizumab和nivolumab是安全的，能发挥抗肿瘤作用，可能是术前治疗的有效选择：本研究在 ClinicalTrials.gov 注册为 NCT02946671（注册日期为 2016-10-05）。

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来源期刊

Journal for Immunotherapy of Cancer Biochemistry, Genetics and Molecular Biology-Molecular Medicine

CiteScore

17.70

自引率

4.60%

发文量

522

审稿时长

18 weeks

期刊介绍： The Journal for ImmunoTherapy of Cancer (JITC) is a peer-reviewed publication that promotes scientific exchange and deepens knowledge in the constantly evolving fields of tumor immunology and cancer immunotherapy. With an open access format, JITC encourages widespread access to its findings. The journal covers a wide range of topics, spanning from basic science to translational and clinical research. Key areas of interest include tumor-host interactions, the intricate tumor microenvironment, animal models, the identification of predictive and prognostic immune biomarkers, groundbreaking pharmaceutical and cellular therapies, innovative vaccines, combination immune-based treatments, and the study of immune-related toxicity.