A phase 1/2a study of T3011, an oncolytic HSV expressing IL-12 and PD-1 antibody, administered via intratumoral (IT) injection as monotherapy in advanced solid tumors.

作者：Dongmei Ji, Yao Weitao, Xiangmin Tong, Chenping Zhang, Feng Wang, Zhendong Chen, Yuhong Zhou, Qiang Li, Yaotiao Deng, Gang Huang, Zhiwei Tao, Yulong Zheng, Gang Wang, Guowen Liu, Jing Chen, Xiaohui Niu, Jilong Yang, W. N. Pang, Min Zhao, Xichun Hu · 发表于：Journal of Clinical Oncology · 年份：2023 · DOI：10.1200/jco.2023.41.16_suppl.2520 · 被引用次数：17 · 研究领域：Virus-based gene therapy research、Cancer Research and Treatments、Viral Infectious Diseases and Gene Expression in Insects

2520 Background: T3011, a replication-competent, genetically modified, next-generation oncolytic herpes simplex viruses (oHSV), deletes one copy of ICP34.5 and retains ICP47, thus maximizing replication activity and virulence attenuation of the virus. Moreover, T3011 was inserted with biologically active IL-12 and anti-PD-1 antibody genes. Therefore, while lysing tumor cells, T3011 can significantly improve the tumor microenvironment and elicit the body's specific anti-tumor immunity. Methods: An open-label, dose escalation and expansion study of T3011 administered via IT injection as a single agent in patients (pts) with advanced solid tumors. Pts who progressed on or were intolerable to the standard of care were eligible and received T3011 IT therapy Q2W in several dose cohorts (2.5×10 5 ~ 1×10 8 PFU/mL). The primary endpoints were safety and tolerability. Key secondary endpoints were PK/PD profile, efficacy endpoints including ORR, DCR, DOR, PFS by investigator per RECIST1.1 and OS. Results: As of 18 Jan. 2023, 90 Pts received T3011 monotherapy. Median follow-up time is 5.7(0.5-22.5) months. No DLT events were reported. Treatment-related adverse events (TRAEs) were observed in 66.7% pts (≥G3 TRAEs and treatment discontinuation both in 2.2% [2/90]), and treatment-related SAEs occurred in 2.2% (2/90) pts. The most frequently reported TRAEs (≥5%) were pyrexia (21.1%, 19/90), influenza like illness (8.9%, 8/90), TSH increased (6.7%, 6/90), proteinuria (6.7%, 6/90), facial edem...