Marble 研究的研究设计和基本原理：Atezolizumab (MPDL3280A) 加卡铂和紫杉醇治疗晚期或复发性胸腺癌 (JTD2101) 患者的 II 期试验,Clinical Lung Cancer

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Marble 研究的研究设计和基本原理：Atezolizumab (MPDL3280A) 加卡铂和紫杉醇治疗晚期或复发性胸腺癌 (JTD2101) 患者的 II 期试验
Clinical Lung Cancer ( IF 3.3 ) Pub Date : 2023-05-19 , DOI: 10.1016/j.cllc.2023.05.004
Tetsuhiko Asao ₁ , Takehito Shukuya ₁ , Tomoyasu Mimori ₁ , Yasushi Goto ₂ , Hiroshi Tanaka ₃ , Koichi Takayama ₄ , Yukari Tsubata ₅ , Motoko Tachihara ₆ , Takuji Suzuki ₇ , Kyoichi Kaira ₈ , Ryo Ko ₉ , Yoshitaka Zenke ₁₀ , Hiroaki Akamatsu ₁₁ , Junko Tanizaki ₁₂ , Satoshi Ikeda ₁₃ , Shunichi Sugawara ₁₄ , Hideaki Mizutani ₁₅ , Keita Mori ₁₆ , Kazuhisa Takahashi ₁

Affiliation

Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Japan.
Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Division of Medical Oncology and Respiratory Medicine, Department of Internal Medicine, Shimane University Faculty of Medicine, Shimane, Japan.
Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Hyogo, Japan.
Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Department of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama Medical University, Saitama, Japan.
Division of Thoracic Oncology, Shizuoka Cancer Centre, Shizuoka, Japan.
Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
Internal Medicine III, Wakayama Medical University, Wakayama, Japan.
Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka, Japan.
Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Kanagawa, Japan.
Department of Pulmonary Medicine, Sendai Kousei Hospital, Miyagi, Japan.
Department of Thoracic Oncology, Saitama Cancer Center, Saitama, Japan.
Department of Biostatistics, Clinical Research Support Center, Shizuoka Cancer Center, Shizuoka, Japan.

背景

胸腺癌（TC）是一种罕见的胸腺上皮肿瘤，晚期或复发的TC预后有限。卡铂和紫杉醇联合治疗初治、晚期或复发性 TC 的治疗效果保持不变；因此，需要一种新的治疗策略。抑制程序性细胞死亡 1 (PD-1) 途径（PD-1 及其配体 PD-L1）的免疫检查点阻断已显示出作为 TC 单一疗法的潜力，尽管单一疗法对于既往治疗的 TC 的疗效中等。我们假设抗 PD-L1 抗体 atezolizumab 与卡铂和紫杉醇的组合可有效诱导晚期或复发性 TC 患者的免疫原性细胞死亡。

方法

我们启动了一项多中心、单臂、开放标签的 II 期研究，研究 atezolizumab 联合卡铂和紫杉醇治疗转移性或复发性 TC。符合条件的患者将每 3 周接受一次 atezolizumab 加卡铂和紫杉醇治疗，最多 6 个周期，然后每 3 周接受一次 atezolizumab，最多 2 年，直至出现进展或出现不可接受的毒性。该研究共有47名患者入组，入组期为24个月，随访期为12个月。主要终点是基于独立中央审查的客观缓解率 (ORR)。次要终点是研究者评估的 ORR、疾病控制率、无进展生存期、缓解持续时间、总生存期和安全性。

结果

本研究旨在确定 atezolizumab 联合卡铂和紫杉醇治疗晚期或复发性 TC 患者的安全性和有效性。

试用注册

日本临床试验注册中心 (jRCT)，jRCT2031220144。注册于 2022 年 6 月 18 日，https://jrct.niph.go.jp/en-latest-detail/jRCT2031220144。

"点击查看英文标题和摘要"

Study Design and Rationale for Marble Study: A Phase II Trial of Atezolizumab (MPDL3280A) Plus Carboplatin and Paclitaxel in Patients With Advanced or Recurrent Thymic Carcinoma (JTD2101)

Background

Thymic carcinoma (TC) is a rare thymic epithelial tumor, and advanced or recurrent TC has limited prognosis. Treatment for chemotherapy-naïve, advanced, or recurrent TC remains unchanged with the combination of carboplatin and paclitaxel; therefore, a new treatment strategy is warranted. Immune checkpoint blockades inhibiting the programmed cell death-1 (PD-1) pathway (PD-1 and its ligand, PD-L1) have shown potential as a monotherapy for TC, although the efficacy of monotherapy was moderate for previously treated TC. We hypothesized that the combination of an anti-PD-L1 antibody, atezolizumab, with carboplatin and paclitaxel, would be effective in inducing immunogenic cell death in patients with advanced or recurrent TC.

Methods

We initiated a multicenter, single-arm, open-label phase II study of atezolizumab combined with carboplatin and paclitaxel for metastatic or recurrent TC. Eligible patients will receive atezolizumab plus carboplatin and paclitaxel every 3 weeks for up to 6 cycles, followed by atezolizumab every 3 weeks for up to 2 years until progression or unacceptable toxicity. A total of 47 patients will be enrolled in this study, with a 24-month enrollment period and 12-month follow-up. The primary endpoint is the objective response rate (ORR), based on an independent central review. The secondary endpoints are the investigator-assessed ORR, disease control rate, progression-free survival, duration of response, overall survival, and safety.

Results

This study aims to establish the safety and efficacy of atezolizumab combined with carboplatin and paclitaxel in patients with advanced or recurrent TC.