Department of Internal Medicine, Section on Hematology & Oncology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT 06877, USA.
Future Oncol. 2022 Aug;18(24):2627-2638. doi: 10.2217/fon-2022-0439. Epub 2022 Jun 14.
Patients with advanced, recurrent or metastatic cancer have poor prognosis despite treatment advancements. Vesicular stomatitis virus (VSV)-glycoprotein (GP; BI 1831169) is a chimeric VSV with its neurotropic glycoprotein G replaced by the non-neurotropic GP of the lymphocytic choriomeningitis virus. This live, recombinant oncolytic virus has demonstrated preclinical efficacy as a viral-based immunotherapy due to its interferon-dependent tumor specificity, potent oncolysis and stimulation of antitumor immune activity. Co-administration of the immune checkpoint inhibitor, ezabenlimab (BI 754091), alongside VSV-GP may synergistically enhance antitumor immune activity. Here, we describe the rationale and design of the first-in-human, phase I, dose-escalation study of VSV-GP alone and in combination with the immune checkpoint inhibitor ezabenlimab in patients with advanced, metastatic or relapsed and refractory solid tumors (NCT05155332).
尽管治疗取得了进展,但晚期、复发性或转移性癌症患者的预后仍然较差。水疱性口炎病毒(VSV)-糖蛋白(GP;BI 1831169)是一种嵌合 VSV,其神经嗜性糖蛋白 G 被淋巴细胞性脉络丛脑膜炎病毒的非神经嗜性 GP 取代。这种活的重组溶瘤病毒由于其干扰素依赖性肿瘤特异性、强大的溶瘤作用和刺激抗肿瘤免疫活性,已被证明在临床前具有作为病毒为基础的免疫疗法的疗效。免疫检查点抑制剂 ezabenlimab(BI 754091)与 VSV-GP 联合使用可能会协同增强抗肿瘤免疫活性。在这里,我们描述了在晚期、转移性或复发和难治性实体瘤患者中单独使用 VSV-GP 以及与免疫检查点抑制剂 ezabenlimab 联合使用的首次人体、I 期、剂量递增研究的原理和设计(NCT05155332)。