Lung Cancer, Nonsmall CellPhase 3REFINE-LungNCT05085028
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)
A Phase 3 study testing Pembrolizumab 25 MG/ML [Keytruda] in people with Lung Cancer, Nonsmall Cell, run by Imperial College London at 37 sites in United Kingdom.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Cancer, Nonsmall Cell
- What is being tested?
- Pembrolizumab 25 MG/ML [Keytruda]
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,750 participants
- Where
- 37 sitesUnited Kingdom
- Study dates
- 23 Jun 2022to 31 May 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
37 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Philip Badman contact
37 sites in 1 country
United Kingdom37 sites, 37 recruiting
- Recruiting
Royal Bournemouth Hospital
Bournemouth
Tom Geldart, Tom.geldart@uhd.nhs.uk
- Recruiting
Royal Sussex County Hospital
Brighton
Kam Zaki, Kam.zaki@nhs.net
- Recruiting
Bristol Haematology and Oncology Centre
Bristol
Adam Dangoor, adam.dangoor@uhbw.nhs.uk
- Recruiting
Queen's Hospital
Burton-on-Trent
Manjusha Keni, manjusha.keni@nhs.net
- Not yet recruiting
Cambridge University Hospitals NHS Foundation Trust
Cambridge
Nicola Thompson, nicolathompson3@nhs.net
- Recruiting
East Kent Hospitals University NHS Foundation Trust
Canterbury
Mathilda Cominos, mathilda.cominos@nhs.net
- Recruiting
Velindre Cancer Centre
Cardiff
Paul Shaw, Paul.P.Shaw@wales.nhs.uk
- Recruiting
Colchester Hospital
Colchester
Dakshinamoorthy Muthukumar, Muthu.Kumar@esneft.nhs.uk
- Recruiting
Royal Derby Hospital
Derby
Manjusha Keni, manjusha.keni@nhs.net
- Recruiting
NHS Lothian
Edinburgh
Colin Barrie, Colin.Barrie@nhslothian.scot.nhs.uk
- Recruiting
Royal Devon and Exeter Hospital
Exeter
Petru Belitei, p.belitei@nhs.net
- Recruiting
Beatson West of Scotland Cancer Centre
Glasgow
Ishtiaq Zubairi, Ishtiaq.Zubairi@ggc.scot.nhs.uk
- Recruiting
New Victoria Hospital
Glasgow
Nicola Steele, Nicola.Steele@ggc.scot.nhs.uk
- Not yet recruiting
Royal Surrey NHS Foundation Trust
Guildford
Madeleine Hewish, madeleine.hewish@nhs.net
- Recruiting
Calderdale & Huddersfield NHS Foundation Trust
Huddersfield
Emma Rathbone, Emma.rathbone@cht.nhs.uk
- Recruiting
Ipswich Hospital
Ipswich
Sunil Skaria, sunil.skaria@esneft.nhs.uk
- Recruiting
Kettering General Hospital
Kettering
Georgios Tsaknis, georgios.tsaknis@nhs.net
- Not yet recruiting
NHS Fife
Kirkcaldy
Almudena Cascales, almudena.cascales2@nhslothian.scot.nhs.uk
- Recruiting
Forth Valley Royal Hospital
Larbert
Nicola Steele, Nicola.Steele@ggc.scot.nhs.uk
- Recruiting
Leeds Teaching Hospitals NHS Trust
Leeds
Pooja Jain, pjain@nhs.net
- Recruiting
Leicester Royal Infirmary
Leicester
Samreen Ahmed, samreen.ahmed@uhl-tr.nhs.uk
- Recruiting
The Clatterbridge Cancer Centre NHS Foundation Trust
Liverpool
Tony Pope, tony.pope@nhs.net
- Recruiting
Guys Hospital
London
James Spicer, james.spicer@kcl.ac.uk
- Recruiting
Imperial College Healthcare NHS Trust
London
Joanne Evans, joanne.evans10@nhs.net
- Recruiting
North Middlesex University Hospital NHS Trust
London
George Imseeh, g.imseeh@nhs.net
- Not yet recruiting
St Bartholomew's Hospital
London
Adam Januszewski, adam.januszewski@nhs.net
- Recruiting
The Christie NHS Foundation Trust
Manchester, M20 4BX
Fabio Gomes, fabio.gomes2@nhs.net
the-christie.LungResearchTeam@nhs.net
- Recruiting
Northampton General Hospital NHS Trust
Northampton
Aleksandar Aleksic, aleksandar.aleksic1@nhs.net
- Recruiting
Nottingham University Hospitals NHS Trust
Nottingham
Jason Adhikaree, Jason.Adhikaree2@nuh.nhs.uk
- Recruiting
Peterborough City Hospital
Peterborough
Sarah Treece, streece@nhs.net
- Recruiting
Poole Hospital
Poole
Tom Geldart, Tom.geldart@uhd.nhs.uk
- Recruiting
Queen's Hospital, Barking Havering and Redbridge University Hospitals NHS Trust
Romford
Kathryn Tarver, k.tarver@nhs.net
- Recruiting
Sheffield Teaching Hospitals NHS Foundation Trust
Sheffield
Fiona Taylor, fiona.taylor9@nhs.net
- Recruiting
The Royal Marsden NHS Foundation Trust
Sutton, SM2 5PT
Mary O'Brien, Mary.OBrien@rmh.nhs.uk
- Recruiting
Royal Cornwall Hospital
Truro
Grant Stewart, grantstewart1@nhs.net
- Recruiting
Worthing Hospital
Worthing
Kam Zaki, Kam.zaki@nhs.net
- Recruiting
Yeovil Hospital
Yeovil
Liz Toy, Liz.Toy@somersetft.nhs.uk
About this study
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
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.
Read the 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.
- Conditions
- Lung Cancer, Nonsmall Cell
- Being tested
- Pembrolizumab 25 MG/ML [Keytruda]
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pembrolizumab 25 MG/ML [Keytruda]Drug
Pembrolizumab to be given at 400mg intravenous over 5 different frequencies
| Study group | Role | What they receive |
|---|---|---|
| 6 weekly | Active comparator | 6 weekly pembrolizumab, 400mg intravenous Receives: Drug: Pembrolizumab 25 MG/ML [Keytruda] |
| 9 weekly | Experimental | 9 weekly pembrolizumab, 400mg intravenous Receives: Drug: Pembrolizumab 25 MG/ML [Keytruda] |
| 12 weekly | Experimental | 12 weekly pembrolizumab, 400mg intravenous Receives: Drug: Pembrolizumab 25 MG/ML [Keytruda] |
| 15 weekly | Experimental | 15 weekly pembrolizumab, 400mg intravenous Receives: Drug: Pembrolizumab 25 MG/ML [Keytruda] |
| 18 weekly | Experimental | 18 weekly pembrolizumab, 400mg intravenous Receives: Drug: Pembrolizumab 25 MG/ML [Keytruda] |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 18 months from randomisation
Secondary outcomes (5)
Overall survival from study entry
Survival, defined as from commencing pembrolizumab (18 months after randomisation) to death due to any cause or study termination
Measured: 2 years
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
Measured: 2 years
Overall response rate
Overall response rate (ORR) as assessed by RECIST v1.1, defined as complete response (CR) or partial response (PR)
Measured: 2 years
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)
Measured: 2 years
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
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2021
- Study start23 Jun 2022
- Primary completion31 May 2027 (estimated)
- Study completion31 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Lung Cancer, Nonsmall CellStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,750 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute for Health Research, United Kingdom, Medical Research Council, University College, London
- Responsible party
- Sponsor
- Investigators
- Michael Seckl, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05085028
- Sponsor's protocol ID
- C/41/2021
- Other IDs
- 2021-004908-18
- Acronym
- REFINE-Lung
- Status last verified
- Mar 2024
- First submitted
- 5 Oct 2021
- Last updated
- 7 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 37142383
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05085028
- Acronym / sponsor ID
- REFINE-Lung / C/41/2021
- Conditions
- Lung Cancer, Nonsmall Cell
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 1,750 participants (estimated)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- National Institute for Health Research, United Kingdom, Medical Research Council, University College, London
- Study start
- 23 Jun 2022 (actual)
- Primary completion
- 31 May 2027 (estimated)
- Study completion
- 31 May 2027 (estimated)
- First posted
- 20 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| 6 weekly | Active comparator | Drug: Pembrolizumab 25 MG/ML [Keytruda]6 weekly pembrolizumab, 400mg intravenous |
| 9 weekly | Experimental | Drug: Pembrolizumab 25 MG/ML [Keytruda]9 weekly pembrolizumab, 400mg intravenous |
| 12 weekly | Experimental | Drug: Pembrolizumab 25 MG/ML [Keytruda]12 weekly pembrolizumab, 400mg intravenous |
| 15 weekly | Experimental | Drug: Pembrolizumab 25 MG/ML [Keytruda]15 weekly pembrolizumab, 400mg intravenous |
| 18 weekly | Experimental | Drug: Pembrolizumab 25 MG/ML [Keytruda]18 weekly pembrolizumab, 400mg intravenous |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pembrolizumab 25 MG/ML [Keytruda]Pembrolizumab to be given at 400mg intravenous over 5 different frequencies | Drug | 12 weekly, 15 weekly, 18 weekly, 6 weekly, 9 weekly |
Primary outcome
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
5 secondary outcomes
Overall survival from study entry
Time frame: 2 years
Progression free survival
Time frame: 2 years
Overall response rate
Time frame: 2 years
Duration of response
Time frame: 2 years
Incidence of adverse events
Time frame: 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2024.
- Derived from this study: PubMed 37142383Ghorani 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Philip Badman contact
Michael Seckl principal investigator
Imperial College London
37 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Pembrolizumab 25 MG/ML [Keytruda] in people with Lung Cancer, Nonsmall Cell, run by Imperial College London at 37 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 7 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 37 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Alex Baker (020 7594 2180, a.williams@imperial.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall survival at 2 years (time frame: 18 months from randomisation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05085028, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Mar 2024.