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) (REFINE-Lung)

March 6, 2024 updated by: Imperial College London

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

1750

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United Kingdom
      • Bournemouth, United Kingdom
      • Brighton, United Kingdom
        • Recruiting
        • Royal Sussex County Hospital
        • Contact:
      • Bristol, United Kingdom
      • Burton Upon Trent, United Kingdom
      • Cambridge, United Kingdom
        • Not yet recruiting
        • Cambridge University Hospitals NHS Foundation Trust
        • Contact:
      • Canterbury, United Kingdom
        • Recruiting
        • East Kent Hospitals University NHS Foundation Trust
        • Contact:
      • Cardiff, United Kingdom
      • Colchester, United Kingdom
      • Derby, United Kingdom
      • Edinburgh, United Kingdom
      • Exeter, United Kingdom
        • Recruiting
        • Royal Devon and Exeter Hospital
        • Contact:
      • Glasgow, United Kingdom
      • Glasgow, United Kingdom
      • Guildford, United Kingdom
      • Huddersfield, United Kingdom
      • Ipswich, United Kingdom
      • Kettering, United Kingdom
      • Kirkcaldy, United Kingdom
      • Larbert, United Kingdom
      • Leeds, United Kingdom
        • Recruiting
        • Leeds Teaching Hospitals NHS Trust
        • Contact:
      • Leicester, United Kingdom
      • Liverpool, United Kingdom
        • Recruiting
        • The Clatterbridge Cancer Centre NHS Foundation Trust
        • Contact:
      • London, United Kingdom
        • Recruiting
        • North Middlesex University Hospital NHS Trust
        • Contact:
      • London, United Kingdom
      • London, United Kingdom
      • London, United Kingdom
      • Manchester, United Kingdom, M20 4BX
      • Northampton, United Kingdom
      • Nottingham, United Kingdom
      • Peterborough, United Kingdom
        • Recruiting
        • Peterborough City Hospital
        • Contact:
      • Poole, United Kingdom
      • Romford, United Kingdom
        • Recruiting
        • Queen's Hospital, Barking Havering and Redbridge University Hospitals NHS Trust
        • Contact:
      • Sheffield, United Kingdom
        • Recruiting
        • Sheffield Teaching Hospitals NHS Foundation Trust
        • Contact:
      • Sutton, United Kingdom, SM2 5PT
      • Truro, United Kingdom
      • Worthing, United Kingdom
      • Yeovil, United Kingdom

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 6 weekly
6 weekly pembrolizumab, 400mg intravenous
Drug: Pembrolizumab 25 MG/ML [Keytruda]
Pembrolizumab to be given at 400mg intravenous over 5 different frequencies
Experimental: 9 weekly
9 weekly pembrolizumab, 400mg intravenous
Drug: Pembrolizumab 25 MG/ML [Keytruda]
Pembrolizumab to be given at 400mg intravenous over 5 different frequencies
Experimental: 12 weekly
12 weekly pembrolizumab, 400mg intravenous
Drug: Pembrolizumab 25 MG/ML [Keytruda]
Pembrolizumab to be given at 400mg intravenous over 5 different frequencies
Experimental: 15 weekly
15 weekly pembrolizumab, 400mg intravenous
Drug: Pembrolizumab 25 MG/ML [Keytruda]
Pembrolizumab to be given at 400mg intravenous over 5 different frequencies
Experimental: 18 weekly
18 weekly pembrolizumab, 400mg intravenous
Drug: Pembrolizumab 25 MG/ML [Keytruda]
Pembrolizumab to be given at 400mg intravenous over 5 different frequencies

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival at 2 years
Time Frame: 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
18 months from randomisation

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Imperial College London

Collaborators

University College, London
Medical Research Council
National Institute for Health Research, United Kingdom

Investigators

  • Principal Investigator: Michael Seckl, Imperial College London

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 23, 2022

Primary Completion (Estimated)

May 31, 2027

Study Completion (Estimated)

May 31, 2027

Study Registration Dates

First Submitted

October 5, 2021

First Submitted That Met QC Criteria

October 18, 2021

First Posted (Actual)

October 20, 2021

Study Record Updates

Last Update Posted (Actual)

March 7, 2024

Last Update Submitted That Met QC Criteria

March 6, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • C/41/2021
  • 2021-004908-18 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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