JME-001 期临床试验：顺铂、培美曲塞和纳武利尤单抗一线联合化疗治疗不可切除恶性胸膜间皮瘤。
JME-001 phase II trial of first-line combination chemotherapy with cisplatin, pemetrexed, and nivolumab for unresectable malignant pleural mesothelioma.
机构信息
Department of Medical Oncology, Okayama Rosai Hospital, Okayama, Japan.
Department of Thoracic Oncology and Medicine, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan.
出版信息
J Immunother Cancer. 2021 Oct;9(10). doi: 10.1136/jitc-2021-003288.
BACKGROUND
JME-001 is a phase II trial assessing the efficacy and safety of cisplatin, pemetrexed, and nivolumab as first-line therapy in malignant pleural mesothelioma (MPM).
PATIENTS AND METHODS
Patients with untreated, unresectable MPM with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1 were included. The primary endpoint is the centrally reviewed objective response rate. The secondary endpoints include (1) response rate assessed by investigators, (2) disease control rate, (3) overall survival, (4) progression-free survival, (5) duration of response, and (6) time to response. Safety and adverse events will also be evaluated. Cisplatin (75 mg/m), pemetrexed (500 mg/m), and nivolumab (360 mg/body) were administered intravenously every 3 weeks with a total of 4-6 cycles. If patients did not progress during the combination phase, maintenance therapy with nivolumab was administered until disease progression or unacceptable toxicity. Tissue samples were required and collected for programmed death ligand 1 analysis.
RESULTS
Eighteen patients (mean age 69.2 years, 15 men) were enrolled between January 2018 and May 2019. The ECOG PS was 0 in 3 patients and 1 in 15 patients. Fourteen (77.8%; 95% CI 52.4% to 93.6%) patients had an objective response. The disease control rate was 94.4% (95% CI 72.7% to 99.9%). Fourteen (77.8%) patients had partial response (PR), three had stable disease, and one was not evaluable. Tumor shrinkage was observed in 10/14 (71.4%) patients with epithelioid, and 2/2 (100%) patients with sarcomatoid or biphasic histological subtype had PR. Ten (55.6%) patients experienced grade 3 or worse adverse events, including disorder of metabolism or nutrition (33.3%), loss of appetite (27.8%), anemia (16.7%), and hyponatremia (11.1%). No treatment-related deaths occurred.
CONCLUSIONS
The safety and efficacy of this study strongly support a definitive trial of this combination.UMIN000030892.
背景
JME-001 是一项评估顺铂、培美曲塞和纳武利尤单抗作为一线治疗恶性胸膜间皮瘤（MPM）的疗效和安全性的 II 期试验。
患者和方法
纳入未经治疗、不可切除的 MPM 患者，东部肿瘤协作组（ECOG）体能状态（PS）为 0-1。主要终点是中心审查的客观缓解率。次要终点包括（1）研究者评估的缓解率，（2）疾病控制率，（3）总生存期，（4）无进展生存期，（5）缓解持续时间，以及（6）缓解时间。安全性和不良事件也将进行评估。顺铂（75mg/m）、培美曲塞（500mg/m）和纳武利尤单抗（360mg/体）每 3 周静脉输注一次，共 4-6 个周期。如果患者在联合治疗期间未进展，则给予纳武利尤单抗维持治疗，直至疾病进展或出现不可接受的毒性。需要并收集组织样本进行程序性死亡配体 1 分析。
结果
2018 年 1 月至 2019 年 5 月期间共纳入 18 例患者（平均年龄 69.2 岁，15 例男性）。ECOG PS 为 0 的有 3 例，1 的有 15 例。14 例（77.8%；95%CI 52.4%至 93.6%）患者有客观缓解。疾病控制率为 94.4%（95%CI 72.7%至 99.9%）。14 例（77.8%）患者有部分缓解（PR），3 例患者病情稳定，1 例患者无法评估。10/14 例（71.4%）上皮样组织学亚型和 2/2 例（100%）肉瘤样或双向组织学亚型患者的肿瘤缩小。10 例（55.6%）患者发生 3 级或更高级别的不良事件，包括代谢或营养紊乱（33.3%）、食欲不振（27.8%）、贫血（16.7%）和低钠血症（11.1%）。无治疗相关死亡。
结论
该研究的安全性和疗效强烈支持该联合治疗的进一步确证性试验。UMIN000030892。
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