Biopsy Support with Patients with Advanced Melanoma

NCI方案：S1607“一项联合Tamilogene Laherparpvec(T-VEC)(NSC-785349)和MK-3475(Pembrolizumab)(NSC-776864)治疗在抗PD1/L1基础治疗方面取得进展的晚期黑色素瘤患者的第二阶段研究。 Talimogene laherparepvec(T-VEC，以前称为OncoVEXGM-CSF)是一种基于改良的单纯疱疹病毒1型(HSV-1)的溶瘤病毒。它旨在选择性地在肿瘤组织中复制，并刺激局部和全身的抗肿瘤免疫反应。瘤内给药可导致肿瘤细胞溶瘤、子代病毒和肿瘤细胞抗原的局部释放。病毒病原体是干扰素反应的强烈诱导者，它们在肿瘤内注射会导致肿瘤微环境的变化，从而更容易产生T细胞反应。此外，转基因病毒的产物GM-CSF也在当地生产，以招募和刺激抗原呈递细胞。总体而言，这一策略有望通过肿瘤溶解来破坏注射的肿瘤，并通过全身抗肿瘤免疫反应来破坏未注射的病变部位(包括微转移)。 队列A(患有内脏疾病)将采用两阶段设计，目标是总共17名符合条件的患者。这包括9名符合条件的第一阶段患者和8名符合条件的第二阶段患者。队列A的预期累计率为每月1名患者。假设不合格率为10%，我们将累积19名患者(第一阶段10名患者，第二阶段9名患者)，以登记17名符合条件的患者 队列B(没有内脏疾病)将采用两阶段设计，目标是总共25名符合条件的患者。这包括16名第一阶段患者和9名第二阶段患者。假设不合格率为10%，我们将累积28名病人，以登记25名合资格的病人。

NCI Protocol: S1607 “A Phase II Study of Combining Tamilogene Laherparpvec (T-VEC) (NSC-785349) and MK-3475 (Pembrolizumab) (NSC-776864) in Patients with Advanced Melanoma Who have Progressed on Anti-PD1/L1 Based Therapy.” Talimogene laherparepvec (T-VEC, formerly known as OncoVEXGM-CSF) is an oncolytic virus based on a modified herpes simplex virus type-1 (HSV-1). It is designed to selectively replicate in tumor tissue and to stimulate local and systemic antitumor immune response. Intralesional administration of talimogene laherparepvec (T-VEC) results in oncolysis of tumor cells and local release of progeny virus as well as of tumor cell antigens. Viral pathogens are strong inducers of interferon responses, and their intratumoral injection results in a change in the tumor microenvironment that is more permissive to a T-cell response. Furthermore, GM-CSF, the product of the viral transgene, is also produced locally to recruit and stimulate antigen-presenting cells. Overall, this strategy is expected to result in the destruction of injected tumors via oncolysis and also uninjected sites of disease (including micro-metastases) via a systemic antitumor immune response. Cohort A (with visceral disease) will use a 2-stage design with an accrual goal of 17 eligible patients in total. This includes 9 eligible patients in the first stage and 8 eligible patients in the second stage. The anticipated accrual rate for Cohort A is 1 patient per month. Assuming an ineligibility rate of 10%, we will accrue 19 total patients (10 patients in the first stage and 9 patients in the second stage) to enroll 17 eligible patients Cohort B (with NO visceral disease) will use a 2-stage design with an accrual goal of 25 eligible patients in total. This includes 16 patients in the first stage and 9 patients in the second stage. Assuming an ineligibility rate of 10%, we will accrue 28 total patients to enroll 25 eligible patients.