Clinical trial NCT05085028: 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)
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Lung Cancer, Nonsmall Cell
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: National Institute for Health Research, United Kingdom
name: Medical Research Council
name: University College, London
First posted: 2021-10-20
Enrollment: 1750
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Overall survival at 2 years
timeFrame: 18 months from randomisation
Secondary outcomes:
measure: Overall survival from study entry
timeFrame: 2 years
measure: Progression free survival
timeFrame: 2 years
measure: Overall response rate
timeFrame: 2 years
measure: Duration of response
timeFrame: 2 years
measure: Incidence of adverse events
timeFrame: 2 years
Other outcomes:
Locations:
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital
city: Brighton
country: United Kingdom
facility: Royal Sussex County Hospital
city: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology Centre
city: Burton Upon Trent
country: United Kingdom
facility: Queen's Hospital
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust
city: Canterbury
country: United Kingdom
facility: East Kent Hospitals University NHS Foundation Trust
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Centre
city: Colchester
country: United Kingdom
facility: Colchester Hospital
city: Derby
country: United Kingdom
facility: Royal Derby Hospital
city: Edinburgh
country: United Kingdom
facility: NHS Lothian
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: Glasgow
country: United Kingdom
facility: New Victoria Hospital
city: Guildford
country: United Kingdom
facility: Royal Surrey NHS Foundation Trust
city: Huddersfield
country: United Kingdom
facility: Calderdale & Huddersfield NHS Foundation Trust
city: Ipswich
country: United Kingdom
facility: Ipswich Hospital
city: Kettering
country: United Kingdom
facility: Kettering General Hospital
city: Kirkcaldy
country: United Kingdom
facility: NHS Fife
city: Larbert
country: United Kingdom
facility: Forth Valley Royal Hospital
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals NHS Trust
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: Liverpool
country: United Kingdom
facility: The Clatterbridge Cancer Centre NHS Foundation Trust
city: London
country: United Kingdom
facility: Guys Hospital
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
city: London
country: United Kingdom
facility: North Middlesex University Hospital NHS Trust
city: London
country: United Kingdom
facility: St Bartholomew's Hospital
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Northampton
country: United Kingdom
facility: Northampton General Hospital NHS Trust
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
city: Peterborough
country: United Kingdom
facility: Peterborough City Hospital
city: Poole
country: United Kingdom
facility: Poole Hospital
city: Romford
country: United Kingdom
facility: Queen's Hospital, Barking Havering and Redbridge University Hospitals NHS Trust
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS Foundation Trust
city: Sutton
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital
city: Worthing
country: United Kingdom
facility: Worthing Hospital
city: Yeovil
country: United Kingdom
facility: Yeovil Hospital
Study officials:
affiliation: Imperial College London
name: Michael Seckl
role: PRINCIPAL_INVESTIGATOR
References: