A Phase 1b Open Label Study of Pembrolizumab for Unresectable or Metastatic Basal Cell Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Overall Response Rate (ORR)
研究概览
简要总结
This phase 1-2 trial studies how well pembrolizumab with or without vismodegib works in treating patients with skin basal cell cancer that has spread to other places in the body or cannot be removed by surgery. Monoclonal antibodies, such as pembrolizumab, are checkpoint inhibitors that stimulate immune response. Vismodegib may stop the growth of tumor cells by blocking signals needed for cell growth.
详细描述
This study is a non-randomized evaluation of pembrolizumab as a treatment for unresectable or metastatic basal cell carcinoma (BCC). Participants are assigned to treatment with pembrolizumab plus vismodegib or pembrolizumab monotherapy on the basis of suitability for treatment with smoothened (SMO) inhibitors such as vismodegib. Prospective participants who have progressed on vismodegib, are intolerant to or have a medical contra-indication to vismodegib may receive pembrolizumab monotherapy. Because treatment is non-randomized, no comparison between treatment groups is conducted.
PRIMARY OBJECTIVE To assess the overall response rate (ORR) of unresectable or metastatic BCC patients to pembrolizumab with or without vismodegib (all evaluable patients) at 18 weeks
SECONDARY OBJECTIVES
- To assess the ORR of unresectable or metastatic BCC patients to pembrolizumab monotherapy at 18 weeks
- To assess the ORR of unresectable or metastatic BCC patients to pembrolizumab monotherapy at 9 weeks
- To assess ORR of unresectable or metastatic BCC patients to pembrolizumab plus vismodegib at 18 weeks
- To assess ORR of unresectable or metastatic BCC patients to pembrolizumab plus vismodegib at 9 weeks
- To assess the safety and tolerability of pembrolizumab (either monotherapy or combination therapy) for unresectable or metastatic BCC.
- To assess the duration of response after pembrolizumab (either monotherapy or combination therapy)
- Incidence and severity of adverse events
- Correlative studies including programmed death-ligand 1 (PD-L1) expression pre-treatment, lymphocytic infiltrates pre- and post-treatment, mutational analysis pre- and post-treatment
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Pembrolizumab Monotherapy
Participants who previously received vismodegib and subsequently progressed will receive pembrolizumab IV over 30 minutes on day 1. Cycles are every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity.
干预措施: Pembrolizumab (Biological)
Pembrolizumab plus Vismodegib Combination Therapy
Participants who have not progressed while receiving vismodegib will receive pembrolizumab IV over 30 minutes on day 1 and take vismodegib 150 mg by mouth daily. Cycles repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity.
干预措施: Pembrolizumab (Biological)
Pembrolizumab plus Vismodegib Combination Therapy
Participants who have not progressed while receiving vismodegib will receive pembrolizumab IV over 30 minutes on day 1 and take vismodegib 150 mg by mouth daily. Cycles repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity.
干预措施: Vismodegib (Drug)
结局指标
主要结局
Overall Response Rate (ORR)
时间窗: 18 weeks
The overall response rate (ORR) of participants with unresectable or metastatic basal cell carcinoma (BCC) after treatment with A) pembrolizumab monotherapy and B) pembrolizumab in combination with vismodegib, will be assessed as the percentage of participants with partial response (PR) or complete response (CR) as determined by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 criteria, after 9 and 18 weeks of treatment. ORR is calculated as the ratio of patients with CR or PR as a percentage of the participants evaluable for OR. RECIST criteria: * Complete Response (CR) = Disappearance of all target lesions * Partial Response (PR) = ≥ 30% decrease in the sum of the longest diameter of target lesions * Overall Response (OR) = CR + PR * Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s) * Stable disease (SD) = Small changes that do not meet any of the above criteria
次要结局
- Percentage of Participants Experiencing Adverse Events(up to 2 years)
- Related Adverse Events(up to 2 years)
- Duration of Response (DOR)(up to 2 years)
- Overall Survival (OS)(1 year)
- Progression-free Survival (PFS)(1 year)
研究者
Anne Chang
Associate Professor of Dermatology
Stanford University