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)

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Pembrolizumab 25 MG/ML [Keytruda]
  Pembrolizumab to be given at 400mg intravenous over 5 different frequencies

Первичные конечные точки

• Overall survival at 2 years [Срок оценки: 18 months from randomisation]

Вторичные конечные точки (5)

• Overall survival from study entry [Срок оценки: 2 years]
• Progression free survival [Срок оценки: 2 years]
• Overall response rate [Срок оценки: 2 years]
• Duration of response [Срок оценки: 2 years]
• Incidence of adverse events [Срок оценки: 2 years]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Великобритания · 37 центров

• Royal Bournemouth Hospital — Bournemouth
• Royal Sussex County Hospital — Brighton
• Bristol Haematology and Oncology Centre — Bristol
• Queen's Hospital — Burton-on-Trent
• Cambridge University Hospitals NHS Foundation Trust — Cambridge
• East Kent Hospitals University NHS Foundation Trust — Canterbury
• Velindre Cancer Centre — Cardiff
• Colchester Hospital — Colchester
• … и ещё 29 центров

Публикации

• Ghorani E, Quartagno M, Blackhall F, Gilbert DC, O'Brien M, Ottensmeier C, Pizzo E, Spicer J, Williams A, Badman P, Parmar MKB, Seckl MJ; REFINE-Lung Investigators. REFINE-Lung implements a novel multi-arm randomised trial design to address possible immunotherapy overtreatment. Lancet Oncol. 2023 May;24(5):e219-e227. doi: 10.1016/S1470-2045(23)00095-5. PMID 37142383

Идентификаторы

NCT: NCT05085028 · C/41/2021 · 2021-004908-18

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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