A Phase 1b/3 Multicenter, Randomized, Trial of Talimogene Laherparepvec in Combination With Pembrolizumab for the Treatment of Subjects With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Number of Participants With a Dose Limiting Toxicity (DLT)
研究概览
简要总结
The primary objective of this study was to evaluate the safety, as assessed by incidence of dose limiting toxicity (DLT), of talimogene laherparepvec in combination with pembrolizumab in adults with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN).
详细描述
This is a phase 1b/3, multicenter, clinical trial conducted in 2 parts (phase 1b and phase 3). In phase 1b talimogene laherparepvec is to be administered in combination with pembrolizumab to adults with recurrent or metastatic squamous cell carcinoma of head and neck (SCCHN). Dose limiting toxicity (DLT) is to be evaluated based on the first 18 DLT-evaluable participants. An expansion cohort of up to an additional 22 treated patients could be enrolled to further evaluate the safety and to estimate the efficacy of the combination of talimogene laherparepvec with pembrolizumab and to support a decision to initiate the phase 3 part of the study. The phase 3 part of the study was designed as a multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy, as assessed by overall survival, of treatment with talimogene laherparepvec with pembrolizumab versus placebo with pembrolizumab in adults with recurrent or metastatic SCCHN, however, a decision was made not to proceed to the phase 3 part of the study.
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
盲法说明
For Phase 1b there are no 'maskings' as it's open-label.
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Talimogene Laherparepvec + Pembrolizumab
Talimogene laherparepvec is 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 3 weeks after the initial dose and every 3 weeks (Q3W) thereafter. Pembrolizumab is administered by intravenous infusion at a dose of 200 mg Q3W after the initial dose. Participants are treated until complete response, no injectable lesions, confirmed disease progression, intolerance of study treatment, 24 months from the date of the first dose of talimogene laherparepvec, or end of study, whichever occurred first.
干预措施: Talimogene Laherparepvec (Drug)
Talimogene Laherparepvec + Pembrolizumab
Talimogene laherparepvec is 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 3 weeks after the initial dose and every 3 weeks (Q3W) thereafter. Pembrolizumab is administered by intravenous infusion at a dose of 200 mg Q3W after the initial dose. Participants are treated until complete response, no injectable lesions, confirmed disease progression, intolerance of study treatment, 24 months from the date of the first dose of talimogene laherparepvec, or end of study, whichever occurred first.
干预措施: Pembrolizumab (Biological)
结局指标
主要结局
Number of Participants With a Dose Limiting Toxicity (DLT)
时间窗: First 6 weeks after the initial administration of talimogene laherparepvec and pembrolizumab in combination
The following toxicities (graded per the Common Terminology Criteria for Adverse Events v 4.0) were considered DLTs if judged by the investigator to be related to either study drug: * grade 4 non-hematologic (non-laboratory) toxicity * ≥ grade 3 pneumonitis * grade 3 non-hematologic toxicity for \> 3 days with optimal supportive care * grade 3 fatigue was not classified as DLT, regardless of duration * any ≥ grade 3 non-hematologic laboratory value if: * medical intervention was required, * the abnormality led to hospitalization, or * the abnormality persisted at ≥ grade 3 for \> 1 week unless deemed not clinically important by investigator and sponsor * grade 3 or 4 febrile neutropenia * thrombocytopenia \< 25 x 10⁹/L associated with bleeding event requiring intervention * serious herpetic event: herpetic encephalitis, encephalomyelitis, or disseminated herpetic infection * grade 5 toxicity * other intolerable toxicity leading to permanent discontinuation of either study drug.
次要结局
- Complete Response Rate(Up to the primary analysis data cutoff date of 02 November 2017; median (minimum, maximum) time on follow-up was 14.36 (1.4, 67.0) weeks.)
- Objective Response Rate(Up to the primary analysis data cutoff date of 02 November 2017; median (minimum, maximum) time on follow-up was 14.36 (1.4, 67.0) weeks.)
- Disease Control Rate(Up to the primary analysis data cutoff date of 02 November 2017; median (minimum, maximum) time on follow-up was 14.36 (1.4, 67.0) weeks.)
- Number of Participants With Adverse Events(From first dose of study drug to 30 days after last dose; the median (range) duration of treatment was 5.6 (0.1 to 75.3) weeks for talimogene laherparepvec and 6.1 (0.1, 105.3) weeks for pembrolizumab.)
- Best Overall Confirmed Response(Up to the primary analysis data cutoff date of 02 November 2017; median (minimum, maximum) time on follow-up was 14.36 (1.4, 67.0) weeks.)
- Progression Free Survival(Up to the primary analysis data cutoff date of 02 November 2017; median (minimum, maximum) time on follow-up was 14.36 (1.4, 67.0) weeks.)
- Overall Survival(Up to the primary analysis data cutoff date of 02 November 2017; median (minimum, maximum) time on follow-up was 14.36 (1.4, 67.0) weeks.)
- Duration of Confirmed Response(Up to the primary analysis data cutoff date of 02 November 2017; median (minimum, maximum) time on follow-up was 14.36 (1.4, 67.0) weeks.)