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)

Lung Cancer, Nonsmall Cell Clinical Trial

— REFINE-Lung  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05085028
• Other study ID #: C/41/2021
• Secondary ID: 2021-004908-18
• Status: Recruiting
• Phase: Phase 3
• Start date: June 23, 2022
• Est. completion date: May 31, 2027

Study information

• Verified date: March 2024
• Source: Imperial College London
• Contact: Alex Baker
• Phone: 020 7594 2180
• Email: a.williams[@]imperial.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 1750
• Est. completion date: May 31, 2027
• Est. primary completion date: May 31, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer, Nonsmall Cell
• Lung Neoplasms

Intervention

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

Locations

Country	Name	City	State
United Kingdom	Royal Bournemouth Hospital	Bournemouth
United Kingdom	Royal Sussex County Hospital	Brighton
United Kingdom	Bristol Haematology and Oncology Centre	Bristol
United Kingdom	Queen's Hospital	Burton Upon Trent
United Kingdom	Cambridge University Hospitals NHS Foundation Trust	Cambridge
United Kingdom	East Kent Hospitals University NHS Foundation Trust	Canterbury
United Kingdom	Velindre Cancer Centre	Cardiff
United Kingdom	Colchester Hospital	Colchester
United Kingdom	Royal Derby Hospital	Derby
United Kingdom	NHS Lothian	Edinburgh
United Kingdom	Royal Devon and Exeter Hospital	Exeter
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	New Victoria Hospital	Glasgow
United Kingdom	Royal Surrey NHS Foundation Trust	Guildford
United Kingdom	Calderdale & Huddersfield NHS Foundation Trust	Huddersfield
United Kingdom	Ipswich Hospital	Ipswich
United Kingdom	Kettering General Hospital	Kettering
United Kingdom	NHS Fife	Kirkcaldy
United Kingdom	Forth Valley Royal Hospital	Larbert
United Kingdom	Leeds Teaching Hospitals NHS Trust	Leeds
United Kingdom	Leicester Royal Infirmary	Leicester
United Kingdom	The Clatterbridge Cancer Centre NHS Foundation Trust	Liverpool
United Kingdom	Guys Hospital	London
United Kingdom	Imperial College Healthcare NHS Trust	London
United Kingdom	North Middlesex University Hospital NHS Trust	London
United Kingdom	St Bartholomew's Hospital	London
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	Northampton General Hospital NHS Trust	Northampton
United Kingdom	Nottingham University Hospitals NHS Trust	Nottingham
United Kingdom	Peterborough City Hospital	Peterborough
United Kingdom	Poole Hospital	Poole
United Kingdom	Queen's Hospital, Barking Havering and Redbridge University Hospitals NHS Trust	Romford
United Kingdom	Sheffield Teaching Hospitals NHS Foundation Trust	Sheffield
United Kingdom	The Royal Marsden NHS Foundation Trust	Sutton
United Kingdom	Royal Cornwall Hospital	Truro
United Kingdom	Worthing Hospital	Worthing
United Kingdom	Yeovil Hospital	Yeovil

Sponsors (4)

Lead Sponsor	Collaborator
Imperial College London	Medical Research Council, National Institute for Health Research, United Kingdom, University College, London

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival at 2 years	Survival at 2 years, defined as from commencing pembrolizumab (18 months after randomisation) to death due to any cause or study termination	18 months from randomisation
Secondary	Overall survival from study entry	Survival, defined as from commencing pembrolizumab (18 months after randomisation) to death due to any cause or study termination	2 years
Secondary	Progression free survival	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	2 years
Secondary	Overall response rate	Overall response rate (ORR) as assessed by RECIST v1.1, defined as complete response (CR) or partial response (PR)	2 years
Secondary	Duration of response	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)	2 years
Secondary	Incidence of adverse events	Safety and tolerability as assessed by adverse events according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0	2 years