A Randomised Open-label Phase III Trial of REduced Frequency Pembrolizumab immuNothErapy for First-line Treatment of Patients With Advanced Non-small Cell Lung Cancer (NSCLC) Utilising a Novel Multi-arm Frequency-response Optimisation Design

Imperial College London37 个研究点分布在 1 个国家目标入组 1,750 人开始时间: 2022年6月23日最近更新: 2024年3月7日

适应症

干预措施

试验速览

阶段: 3 期
状态: 招募中
发起方: Imperial College London
入组人数: 1,750
试验地点: 37
主要终点: Overall survival at 2 years

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

REFINE-lung will test whether reduced pembrolizumab dose frequency after 6 months of standard treatment is safe and effective. Patients treated with 1st line pembrolizumab who are progression free and otherwise planning to continue therapy at 6 months will be initially randomised to control 6 weekly versus interventional 12 weekly therapy. If an interim analysis shows that the 12 weekly treatment is no less effective, subsequent patients will also be randomised to 9, 15 and 18 weekly treatment frequency arms. Patients who progress on a reduced frequency arm will be offered re-escalation to standard 6 weekly therapy.

详细描述

Immunotherapy with pembrolizumab targeting the T cell inhibitory PD-1 receptor has significantly improved outcomes in advanced non-small cell lung cancer (NSCLC). Approximately 3600 new patients are treated in the 1st line setting per year in England alone and up to 25% remain on 6 weekly pembrolizumab for 2 years. However, pharmacological and clinical trial data suggest current frequent dosing for 2 years result in overtreatment. Indeed, pembrolizumab remains bound to its target receptor for up to 100 days following a single dose and studies in multiple tumour types have found no relationship between dose and patient outcome. Moreover, anti-PD1 treated patients who respond but discontinue therapy either as planned after 2 years, or earlier because of toxicity, can either remain in remission and/or be sensitive to re-challenge with pembrolizumab.

REFINE-lung will test whether reduced pembrolizumab dose frequency (9, 12, 15, 18 weeks) after 6 months of standard treatment is safe and effective.

This UK study represents a unique opportunity to determine whether pembrolizumab dose frequency can be safely reduced in NSCLC, resulting in significant cost benefits to the NHS and globally, in addition to enhanced patient QoL associated with fewer hospital attendances and reduced toxicity.

研究设计

研究类型: Interventional
分配方式: 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

•Written informed consent prior to initiation of any study procedures and willingness and ability to comply with the study schedule
•Any patient ≥18yrs who has received 6 months of pembrolizumab treatment with or without chemotherapy for advanced Non small cell lung cancer who is planned to continue immunotherapy treatment because of continued benefit.

排除标准

•Disease progression or not tolerating treatment at 6 months into therapy
•Clinician does not intend to continue immunotherapy
•Any patient with a synchronous primary cancer. This includes any new cancer diagnoses or relapse of previously treated cancer since starting pembrolizumab treatment.
•Any patient currently receiving an investigational agent and/or using an investigational device or has participated in a study of an investigational agent and/or used an investigational device within 28 days of randomisation.