A Phase 2, Multicenter, Open-label, Single-arm Trial to Evaluate the Correlation Between Objective Response Rate and Baseline Intratumoral CD8+ Cell Density in Subjects With Unresected Stage IIIB to IVM1c Melanoma Treated With Talimogene Laherparepvec
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 112
- 试验地点
- 1
- 主要终点
- Odds Ratio of Baseline Intratumoral CD8+ Cell Density and Objective Response Rate
研究概览
简要总结
The study is a phase 2, multi centered, single arm study designed to evaluate the correlation between cluster of differentiation 8-positive (CD8+) cell density and objective response rate in adults with unresected stage IIIB to IVM1c melanoma. This study will also evaluate the safety and tolerability profile of talimogene laherparepvec.
详细描述
The study will explore the hypothesis that intratumoral CD8+ cell density at baseline correlates with objective response rate in adults with unresected stage IIIB to IVMIc melanoma treated with talimogene laherparepvec.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provided informed consent prior to initiation of any study-specific activities/procedures
- •Subject with stage IIIB to IVM1c melanoma for whom surgery is not recommended
- •Candidate for intralesional therapy
- •Measurable disease with greatest diameter ≥ 10 mm
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Adequate organ function
- •Other Inclusion Criteria May Apply
排除标准
- •Clinically active cerebral metastases.
- •Bone metastases
- •Primary ocular or mucosal melanoma
- •Active herpetic skin lesions or prior complications of herpes simplex virus type 1 (HSV-1) infection (eg, herpetic keratitis or encephalitis)
- •Requires intermittent or chronic systemic (intravenous or oral) treatment with an antiherpetic drug (eg, acyclovir), other than intermittent topical use
- •Female subject is pregnant or breast-feeding, or planning to become pregnant during study treatment and through 3 months after the last dose of talimogene laherparepvec
- •Female subject of childbearing potential who is unwilling to use acceptable method(s) of effective contraception
- •Other Exclusion Criteria May Apply
研究组 & 干预措施
Talimogene Laherparepvec
Talimogene laherparepvec was administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 10⁶ plaque-forming units (PFU) per mL on day 1 followed by a dose of 10⁸ PFU/mL 21 days after the initial dose and every 14 days thereafter. Participants were treated with talimogene laherparepvec until they achieved a complete response, all injectable tumors had disappeared, clinically significant (resulting in clinical deterioration or requiring change of therapy) disease progression beyond 6 months of treatment, per modified World Health Organization (WHO) response criteria, or intolerance of study treatment, whichever occurred first.
干预措施: Talimogene Laherparepvec (Drug)
结局指标
主要结局
Odds Ratio of Baseline Intratumoral CD8+ Cell Density and Objective Response Rate
时间窗: Intratumoral CD8+ cell density: Baseline. Response: every 12 weeks until disease progression beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up at primary completion = 59 weeks (min 3 to max 116 weeks)
A univariate logistic regression model was performed to evaluate baseline log2(CD8+ cell density) as a predictor of objective response. Response was assessed according to the modified version of the World Health Organization (WHO) response criteria. Objective response rate (ORR) was defined as the percentage of participants with a complete response (CR) or partial response (PR) according to the modified WHO criteria. The unadjusted odds ratio of log2(baseline intratumoral CD8+ cell density) for objective response rate is reported.
次要结局
- Odds Ratio of Baseline Intratumoral CD8+ Cell Density and Durable Response Rate(Intratumoral CD8+ cell density: Baseline. Response: every 12 weeks until disease progression beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up: PC: 59 weeks (3 to 116 weeks); FA: 108 weeks (2.7 to 245.6))
- Hazards Ratio of Baseline Intratumoral CD8+ Cell Density and Duration of Response(Intratumoral CD8+ cell density: Baseline. Response: every 12 weeks until disease progression beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up: PC: 59 weeks (3 to 116 weeks); FA: 108 weeks (2.7 to 245.6 weeks))
- Correlation Between Baseline Intratumoral CD8+ Cell Density and Changes in Tumor Burden(Intratumoral CD8+ cell density: Baseline; Tumor burden: First dose of study drug until primary completion date (26 June 2017) or end of follow-up; median time on follow-up: PC: 59 weeks (3 to 116 weeks); FA: 108 weeks (2.7 to 245.6 weeks))
- Odds Ratio of Change From Baseline Intratumoral CD8+ Cell Density and Objective Response Rate(CD8+ cell density: Baseline & Week 6. Response: every 12 weeks until disease progression beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up: PC: 59 weeks (3 to 116 weeks); FA: 108 weeks (2.7 to 245.6 weeks))
- Odds Ratio of Change From Baseline in Intratumoral CD8+ Cell Density and Durable Response Rate(CD8+ cell density: Baseline & Week 6. Response: every 12 weeks until disease progression beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up: PC: 59 weeks (3 to 116 weeks); FA: 108 weeks (2.7 to 245.6 weeks))
- Hazard Ratio of Change From Baseline in Intratumoral CD8+ Cell Density and Duration of Response(CD8+ cell density: Baseline & Week 6. Response: every 12 weeks until disease progression beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up: PC: 59 weeks (3 to 116 weeks); FA: 108 weeks (2.7 to 245.6 weeks))
- Correlation Between Change From Baseline in Intratumoral CD8+ Cell Density and Changes in Tumor Burden(CD8+ cell density: Baseline & Week 6. Response: every 12 weeks until disease progression beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up: PC: 59 weeks (3 to 116 weeks); FA: 108 weeks (2.7 to 245.6 weeks))
- Objective Response Rate(Response was assessed every 12 weeks until PD beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up at time of primary completion: 59 weeks (3 to 116 weeks); final analysis: 108 weeks (2.7 to 245.6 weeks))
- Duration of Response(Response was assessed every 12 weeks until PD beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up at time of primary completion: 59 weeks (3 to 116 weeks); final analysis: 108 weeks (2.7 to 245.6 weeks))
- Time to Treatment Failure(From first dose of study drug until primary completion date of 26 June 2017, or end of follow-up; median time on follow-up at primary completion was 59 weeks (3 to 116 weeks); final analysis was 108 weeks (2.7 to 245.6 weeks))
- Durable Response Rate(Response was assessed every 12 weeks until PD beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up at time of primary completion: 59 weeks (3 to 116 weeks); final analysis: 108 weeks (2.7 to 245.6 weeks))
- Overall Survival(From first dose of study drug until primary completion date of 26 June 2017, or end of follow-up; median time on follow-up at primary completion was 59 weeks (3 to 116 weeks); final analysis was 108 weeks (2.7 to 245.6 weeks))
- Change From Baseline in Tumor Burden(Baseline and Day 1 of cycle 6, 12 , 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, 102, 108, 114, and 120. The first cycle was 21 days and all subsequent cycles were 14 days.)
- Number of Participants With Adverse Events(From first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 weeks (range 0.14 to 241.43 weeks))