ONCOS-102，一种表达粒细胞-巨噬细胞集落刺激因子的溶瘤腺病毒，能改变肿瘤微环境为免疫刺激状态。将ONCOS-102与恶性胸膜间皮瘤（MPM）常规化疗联合应用，可能改善治疗效果。本次开放标签、随机研究中，无法手术切除的MPM患者接受肿瘤内注射ONCOS-102（第1、4、8、36、78和120天，病毒颗粒数为3×1011个），联合培美曲塞（pemetrexed）和顺铂/卡铂（从第22天开始），或仅接受培美曲塞和顺铂/卡铂。主要终点为安全性。同时评估了总生存期（OS）、无进展生存期、客观反应率和肿瘤免疫激活情况（基线和第36天活检）。 共纳入31名患者（安全前导：n=6，随机：n=25）。贫血（ONCOS-102组为15.0%，化疗组为27.3%）和中性粒细胞减少症（ONCOS-102组为40.0%，化疗组为45.5%）是ONCOS-102（n=20）和单独化疗（n=11）队列中最常见的≥3级不良事件（AEs）。无患者因AEs而停止使用ONCOS-102。在疗效终点上未观察到统计学上显著差异。在化疗未经历的患者（n=17）中，ONCOS-102与化疗相比在总生存期方面有数值改善（30个月总生存率为34.1% vs 0；中位总生存期为20.3 vs 13.5个月）。到第36天，ONCOS-102与T细胞浸润和免疫相关基因表达的增加有关，而在对照组中未观察到这种情况。与ONCOS-102队列中18个月存活率相关的是肿瘤微环境中显著的免疫激活作用。 ONCOS-102联合培美曲塞和顺铂/卡铂在MPM患者中耐受良好。在注射肿瘤中，ONCOS-102促进了一种促炎环境，包括T细胞浸润，这与18个月存活相关。 翻译来源：BMJ (British Medical Journal) International Open，2023年，授权CC BY-NC。不可商业再利用。请参阅权利和权限。由BMJ发布。

ONCOS-102, an oncolytic adenovirus expressing granulocyte-macrophage colony-stimulating factor, can alter the tumor microenvironment to an immunostimulatory state. Combining ONCOS-102 with standard-of-care chemotherapy for malignant pleural mesothelioma (MPM) may improve treatment outcomes.In this open-label, randomized study, patients with unresectable MPM received intratumoral ONCOS-102 (3×1011 virus particles on days 1, 4, 8, 36, 78, and 120) and pemetrexed plus cisplatin/carboplatin (from day 22), or pemetrexed plus cisplatin/carboplatin alone. The primary endpoint was safety. Overall survival (OS), progression-free survival, objective response rate, and tumor immunologic activation (baseline and day 36 biopsies) were also assessed.In total, 31 patients (safety lead-in: n=6, randomized: n=25) were enrolled. Anemia (15.0% and 27.3%) and neutropenia (40.0% and 45.5%) were the most frequent grade ≥3 adverse events (AEs) in the ONCOS-102 (n=20) and chemotherapy-alone (n=11) cohorts. No patients discontinued ONCOS-102 due to AEs. No statistically significant difference in efficacy endpoints was observed. There was a numerical improvement in OS (30-month OS rate 34.1% vs 0; median OS 20.3 vs 13.5 months) with ONCOS-102 versus chemotherapy alone in chemotherapy-naïve patients (n=17). By day 36, ONCOS-102 was associated with increased T-cell infiltration and immune-related gene expression that was not observed in the control cohort. Substantial immune activation in the tumor microenvironment was associated with survival at month 18 in the ONCOS-102 cohort.ONCOS-102 plus pemetrexed and cisplatin/carboplatin was well tolerated by patients with MPM. In injected tumors, ONCOS-102 promoted a proinflammatory environment, including T-cell infiltration, which showed association with survival at month 18.© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.