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)
- Conditions
- Lung Cancer, Nonsmall Cell
- Interventions
- Registration Number
- NCT05085028
- Lead Sponsor
- Imperial College London
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 1750
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 12 weekly Pembrolizumab 25 MG/ML [Keytruda] 12 weekly pembrolizumab, 400mg intravenous 15 weekly Pembrolizumab 25 MG/ML [Keytruda] 15 weekly pembrolizumab, 400mg intravenous 18 weekly Pembrolizumab 25 MG/ML [Keytruda] 18 weekly pembrolizumab, 400mg intravenous 6 weekly Pembrolizumab 25 MG/ML [Keytruda] 6 weekly pembrolizumab, 400mg intravenous 9 weekly Pembrolizumab 25 MG/ML [Keytruda] 9 weekly pembrolizumab, 400mg intravenous
- Primary Outcome Measures
Name Time Method Overall survival at 2 years 18 months from randomisation Survival at 2 years, defined as from commencing pembrolizumab (18 months after randomisation) to death due to any cause or study termination
- Secondary Outcome Measures
Name Time Method Overall survival from study entry 2 years Survival, defined as from commencing pembrolizumab (18 months after randomisation) to death due to any cause or study termination
Progression free survival 2 years Progression free survival as assessed by RECIST v1.1, defined as time from study entry to first evidence of disease progression or death due to any cause
Overall response rate 2 years Overall response rate (ORR) as assessed by RECIST v1.1, defined as complete response (CR) or partial response (PR)
Duration of response 2 years Duration of response (DoR) as assessed by RECIST v1.1, defined as time from study entry to change in response from CR or PR to stable disease (SD) or progressive disease (PD)
Incidence of adverse events 2 years Safety and tolerability as assessed by adverse events according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Trial Locations
- Locations (37)
Velindre Cancer Centre
🇬🇧Cardiff, United Kingdom
Royal Bournemouth Hospital
🇬🇧Bournemouth, United Kingdom
Royal Sussex County Hospital
🇬🇧Brighton, United Kingdom
Queen's Hospital
🇬🇧Burton Upon Trent, United Kingdom
New Victoria Hospital
🇬🇧Glasgow, United Kingdom
Royal Cornwall Hospital
🇬🇧Truro, United Kingdom
Ipswich Hospital
🇬🇧Ipswich, United Kingdom
Kettering General Hospital
🇬🇧Kettering, United Kingdom
Leeds Teaching Hospitals NHS Trust
🇬🇧Leeds, United Kingdom
Guys Hospital
🇬🇧London, United Kingdom
The Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom
Sheffield Teaching Hospitals NHS Foundation Trust
🇬🇧Sheffield, United Kingdom
Queen's Hospital, Barking Havering and Redbridge University Hospitals NHS Trust
🇬🇧Romford, United Kingdom
Worthing Hospital
🇬🇧Worthing, United Kingdom
Yeovil Hospital
🇬🇧Yeovil, United Kingdom
East Kent Hospitals University NHS Foundation Trust
🇬🇧Canterbury, United Kingdom
Royal Devon and Exeter Hospital
🇬🇧Exeter, United Kingdom
Imperial College Healthcare NHS Trust
🇬🇧London, United Kingdom
Northampton General Hospital NHS Trust
🇬🇧Northampton, United Kingdom
Nottingham University Hospitals NHS Trust
🇬🇧Nottingham, United Kingdom
The Royal Marsden NHS Foundation Trust
🇬🇧Sutton, United Kingdom
Bristol Haematology and Oncology Centre
🇬🇧Bristol, United Kingdom
Cambridge University Hospitals NHS Foundation Trust
🇬🇧Cambridge, United Kingdom
Colchester Hospital
🇬🇧Colchester, United Kingdom
NHS Lothian
🇬🇧Edinburgh, United Kingdom
Royal Derby Hospital
🇬🇧Derby, United Kingdom
Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, United Kingdom
Royal Surrey NHS Foundation Trust
🇬🇧Guildford, United Kingdom
Calderdale & Huddersfield NHS Foundation Trust
🇬🇧Huddersfield, United Kingdom
NHS Fife
🇬🇧Kirkcaldy, United Kingdom
Forth Valley Royal Hospital
🇬🇧Larbert, United Kingdom
The Clatterbridge Cancer Centre NHS Foundation Trust
🇬🇧Liverpool, United Kingdom
Peterborough City Hospital
🇬🇧Peterborough, United Kingdom
Leicester Royal Infirmary
🇬🇧Leicester, United Kingdom
St Bartholomew's Hospital
🇬🇧London, United Kingdom
Poole Hospital
🇬🇧Poole, United Kingdom
North Middlesex University Hospital NHS Trust
🇬🇧London, United Kingdom