JNJ-64041757 (JNJ-757), a Live, Attenuated, Double-Deleted Listeria monocytogenes-Based Immunotherapy in Patients With NSCLC: Results From Two Phase 1 Studies.
JNJ-64041757 (JNJ-757), a Live, Attenuated, Double-Deleted Listeria monocytogenes-Based Immunotherapy in Patients With NSCLC: Results From Two Phase 1 Studies.
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JNJ-64041757(JNJ-757)，一种基于单核细胞增多性李斯特菌的活体、减毒、双缺失免疫疗法，用于非小细胞肺癌患者：两项第一阶段研究的结果。
DOI：
10.1016/j.jtocrr.2020.100103
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发表时间：
2021-03
影响因子：
--
通讯作者：
Hassan R
中科院分区：
文献类型：
--
作者：
Brahmer JR;Johnson ML;Cobo M;Viteri S;Sarto JC;Sukari A;Awad MM;Salgia R;Papadimitrakopoulou VA;Rajan A;Bandyopadhyay N;Allred AJ;Wade M;Mason GE;Zudaire E;Knoblauch RE;Stone N;Lorenzi MV;Hassan R
JNJ-64041757(JNJ-757)是一种基于表达人间皮蛋白的活的、减毒的、双缺失的单核细胞增生性李斯特菌的免疫疗法。JNJ-757在晚期NSCLC患者中作为单一疗法(1期)和与nivolumab联合治疗(1b/2期)进行评估。对既往治疗过的IIIB/IV期NSCLC患者，单用JNJ-757(1×108或1×109集落形成单位[CFU])或JNJ-757(1×109 CFU)加尼伏单抗240 mg(NCT03371381)治疗。研究目标包括免疫原性、安全性和有效性的评估。在单一疗法研究中，18名患者(中位年龄63.5岁；女性61%)接受JNJ-757(1×108或1×109 CFU)治疗，中位疗程为1.4个月(范围0-29个月)。最常见的不良反应是发热(72%)和寒战(61%)，通常是轻微的，在48小时内消失。在13名生物标记物可评估的患者中，有10名患者在治疗后通过一过性间皮特异性T细胞反应诱导了外周致炎细胞因子和淋巴细胞激活。在单一治疗中，18名可评估反应的患者中有4名患者的病情稳定在16周或更长时间，包括1名目标皮损减少的患者。在联合研究中，12名患者入选(中位年龄63.5岁；女性33%)。联合治疗最常见的不良反应是发热(67%)和寒战(58%)；6名患者有3级或更高的不良反应，包括2例与治疗相关的致命肺炎。在9名可评估反应的患者中，有4名患者的总体反应最好，病情稳定。作为单一疗法，JNJ-757具有免疫原性和耐受性，并有轻微的输液相关发热和寒战。JNJ-757单独或与nivolumab联用的疗效有限，不值得对其联合进行进一步研究。
JNJ-64041757 (JNJ-757) is a live, attenuated, double-deleted Listeria monocytogenes–based immunotherapy expressing human mesothelin. JNJ-757 was evaluated in patients with advanced NSCLC as monotherapy (phase 1) and in combination with nivolumab (phase 1b/2). Patients with stage IIIB/IV NSCLC who had received previous therapy were treated with JNJ-757 (1 × 108 or 1 × 109 colony-forming units [CFUs]) alone (NCT02592967) or JNJ-757 (1 × 109 CFU) plus intravenous nivolumab 240 mg (NCT03371381). Study objectives included the assessment of immunogenicity, safety, and efficacy. In the monotherapy study, 18 patients (median age 63.5 y; women 61%) were treated with JNJ-757 (1 × 108 or 1 × 109 CFU) with a median duration of 1.4 months (range: 0–29). The most common adverse events (AEs) were pyrexia (72%) and chills (61%), which were usually mild and resolved within 48 hours. Peripheral proinflammatory cytokines and lymphocyte activation were induced posttreatment with transient mesothelin-specific T-cell responses in 10 of 13 biomarker-evaluable patients. With monotherapy, four of 18 response-evaluable patients had stable disease of 16 or more weeks, including one patient with a reduction in target lesions. In the combination study, 12 patients were enrolled (median age 63.5 y; women 33%). The most common AEs with combination therapy were pyrexia (67%) and chills (58%); six patients had grade 3 AEs or greater, including two cases of treatment-related fatal pneumonitis. The best overall response for the combination was stable disease in four of nine response-evaluable patients. As monotherapy, JNJ-757 was immunogenic and tolerable, with mild infusion-related fever and chills. The limited efficacy of JNJ-757, alone or with nivolumab, did not warrant further investigation of the combination.
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影响因子：
10.9
作者：
Mkrtichyan M;Chong N;Abu Eid R;Wallecha A;Singh R;Rothman J;Khleif SN
通讯作者：
Khleif SN
影响因子：
8.4
作者：
Giaccone, G.;Bazhenova, L. A.;Fakhrai, H.
通讯作者：
Fakhrai, H.
影响因子：
7.5
作者：
Ordóñez, NG
通讯作者：
Ordóñez, NG
影响因子：
5.8
作者：
Shahabi, Vafa;Reyes-Reyes, Mariela;Maciag, Paulo
通讯作者：
Maciag, Paulo
影响因子：
2.2
作者：
Kushitani, Kei;Takeshima, Yukio;Inai, Kouki
通讯作者：
Inai, Kouki