Supplementary Material for: Clinical efficacy and safety of nivolumab in malignant non-pleural mesothelioma: A multicenter, open-label, single-arm, Japanese phase II trial (VIOLA) protocol

Background: There is no authorized treatment for malignant non-pleural mesothelioma (MNPM) worldwide. In contrast to malignant pleural mesothelioma (MPM), MNPM has not been investigated, and no treatment has been established due to its rarity.
Objectives: This multicenter, open-label, single-arm, Japanese phase II trial aims at evaluating the efficacy and safety of nivolumab, an immune checkpoint inhibitor, in advanced or metastatic MNPM treatment.
Methods: This phase II trial commenced in October 2020. Twenty-three patients with advanced or metastatic MNPM who meet the inclusion and exclusion criteria were enrolled from five institutions within 2 years. Regardless of prior therapy, 240 mg of nivolumab will be administered intravenously to MNPM patients every 2 weeks to investigate its efficacy and safety until disease progression or unacceptable toxicities are detected, or the patient’s condition meets the withdrawal criteria.
Results: The primary endpoint is the objective response rate by central assessment following the Response Evaluation Criteria in Solid Tumors version 1.1. The secondary endpoints include disease control rate, overall survival, progression-free survival, adverse events, and treatment-related adverse events.
Conclusions: This is the first prospective investigator-initiated trial to evaluate the effect of nivolumab monotherapy for MNPM.

背景：目前全球范围内尚无针对恶性非胸膜间皮瘤（malignant non-pleural mesothelioma, MNPM）的获批治疗方案。与恶性胸膜间皮瘤（malignant pleural mesothelioma, MPM）不同，MNPM因发病率极低，相关研究尚未开展，尚未确立任何标准治疗手段。
研究目的：本项多中心、开放标签、单臂日本II期临床试验，旨在评估免疫检查点抑制剂纳武利尤单抗（nivolumab）用于晚期或转移性MNPM治疗的有效性与安全性。
研究方法：本项II期临床试验于2020年10月启动。在2年内从5家研究中心入组符合纳入排除标准的23例晚期或转移性MNPM患者。无论患者既往接受过何种治疗，均将以每2周一次的静脉输注方式给予240mg纳武利尤单抗（nivolumab），直至出现疾病进展、不可耐受的毒性反应，或患者符合试验退出标准为止，以此评估其有效性与安全性。
研究结果：预设主要终点为基于实体瘤疗效评价标准1.1版（Response Evaluation Criteria in Solid Tumors version 1.1, RECIST 1.1）的中央评估客观缓解率。次要终点包括疾病控制率、总生存期、无进展生存期、不良事件及治疗相关不良事件。
研究结论：本试验是首项评估纳武利尤单抗（nivolumab）单药治疗MNPM疗效的前瞻性研究者发起临床试验。