《STOMP》是一项单臂、开放标签的Ⅱ期临床试验，旨在探索体内基因治疗和立体定向放射治疗在转移性非小细胞肺癌（mNSCLC）中与Pembrolizumab联合应用的双重策略。患者接受肿瘤内注射ADV/HSV-tk（5 × 10^11 vp）和SBRT（30 Gy，5分次）治疗，然后每3周静脉注射Pembrolizumab 200 mg，直到疾病进展或无法忍受的毒性反应。主要终点是总体缓解率（CR和PR），次要终点包括临床获益率（CBR，CR，PR和SD），无进展生存期（PFS），总生存期（OS）和安全性。共纳入了28名患者，其中27名患者进行了疗效评估。缓解率为33.3％，包括2例CR（7.4％）和7例PR（25.9％）。CBR为70.4％。其中8例（75.0％）免疫检查点抑制剂（ICI）不敏感的患者获得了临床益处。缓解患者持久反应，无中位无进展生存期和总生存期的报道。而总体人群的中位无进展生存期为7.4个月（95％CI为5.1至9.6个月），总生存期为18.1个月（95％CI为15.4至20.9个月）。该联合治疗方案耐受良好，有6例（21.4％）患者出现3级或更高毒性反应。基于ADV/HSV-tk加瓦拉洛韦基因治疗和SBRT的双重策略，作为化疗替代方案增强Pembrolizumab的抗肿瘤效果，在mNSCLC患者中得到了良好的临床应用，并且疗效显著。版权所有©2023 Elsevier公司。保留所有权利。

A phase 2 study of stereotactic body radiation therapy and in situoncolytic virus therapy in metastatic non-small cell lung cancer (mNSCLC) followed by Pembrolizumab (STOMP) was designed to explore the dual approach in enhancing single pembrolizumab with ADV/HSV-tk plus valacyclovir gene therapy and stereotactic radiotherapy (SBRT) in mNSCLC.STOMP is a single-arm, open-label phase II study. Patients with mNSCLC received intratumoral injections of ADV/HSV-tk (5 × 1011 vp) and SBRT (30 Gy in 5 fractions) followed by pembrolizumab 200 mg IV every 3 weeks until disease progression or intolerable toxicity. The primary end point was ORR (CR and PR). Secondary end points included clinical benefit rate (CBR, CR, PR and SD), PFS, OS and safety.28 patients were enrolled, among which 27 were evaluated for response. The ORR was 33.3% including two CR (7.4%) and seven PR (25.9%). CBR was 70.4%. 6/8 (75.0%) patients who were immune checkpoint inhibitor (ICI) refractory derived clinical benefits. Responders had durable responses with median PFS, and OS not reached. While the total population had a median PFS of 7.4 months (95% CI, 5.1 to 9.6 months), and OS 18.1 months (95%CI, 15.4 to 20.9 months). The combination was well tolerated with Grade 3 or higher toxicity in 6 (21.4%) patients.Dual approach of in situ ADV/HSV-tk plus valacyclovir gene therapy and SBRT as a chemotherapy sparing strategy to enhance anti-tumor effect of pembrolizumab is a well-tolerated encouraging treatment in patients with mNSCLC.Copyright © 2023 Elsevier Inc. All rights reserved.