Biopsy Support with Patients with Advanced Melanoma

晚期黑色素瘤患者的活检支持

• 批准号: 10038623
• 负责人: LEONARD FREEDMAND
• 金额: $ 9万
• 依托单位: LEIDOS BIOMEDICAL RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-31 至 2020-08-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10038623
• 关键词: Antigen-Presenting Cells; Antigens; Biopsy; Disease; Enrollment; Goals; Granulocyte-Macrophage Colony-Stimulating Factor; Herpesvirus 1; In complete remission; Injections; Interferon Inducers; Neoplasm Metastasis; Oncolytic viruses; Patients; Protocols documentation; Site; Skin; T cell response; Transgenes; Tumor Tissue; Viral; Virus; Visceral; anti-PD-1; anti-PD-L1; anti-tumor immune response; base; cohort; design; melanoma; neoplastic cell; objective response rate; oncolysis; partial response; pathogenic virus; phase 2 study; recruit; response; tumor; tumor microenvironment

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.

NCI方案：S1607“一项联合Tamilogene Laherparpvec（T-VEC）（NSC-785349）和MK-3475（Pembrolizumab）（NSC-776864）治疗在基于抗PD 1/L1治疗后进展的晚期黑色素瘤患者的II期研究”。 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。它被设计为选择性地在肿瘤组织中复制并刺激局部和全身抗肿瘤免疫应答。病灶内施用拉他莫基（talimogene laherparepvec，T-VEC）导致肿瘤细胞的溶瘤作用和子代病毒以及肿瘤细胞抗原的局部释放。病毒病原体是干扰素应答的强诱导剂，并且它们的瘤内注射导致肿瘤微环境的变化，这更允许T细胞应答。此外，病毒转基因的产物GM-CSF也在局部产生以募集和刺激抗原呈递细胞。总体而言，预期该策略将通过溶瘤作用破坏注射肿瘤，并通过全身抗肿瘤免疫应答破坏未注射的疾病部位（包括微转移）。 队列A（内脏疾病）将采用2阶段设计，招募目标为总计17例合格患者。这包括第一阶段的9例合格患者和第二阶段的8例合格患者。队列A的预期增加率为每月1例患者。假设不合格率为10%，我们将招募19例患者（第一阶段10例患者，第二阶段9例患者），以招募17例合格患者 队列B（无内脏疾病）将采用2阶段设计，招募目标为总计25例合格患者。 这包括第一阶段的16名患者和第二阶段的9名患者。 假设不合格率为10%，我们将招募28例患者，以招募25例合格患者。