A phase II trial of pembrolizumab in NSCLC PS2 patients

ISRCTN	ISRCTN10047797
DOI	https://doi.org/10.1186/ISRCTN10047797
EudraCT/CTIS number	2015-002241-55
ClinicalTrials.gov number	NCT02733159
Secondary identifying numbers	31307

Submission date: 08/08/2016
Registration date: 11/08/2016
Last edited: 06/02/2024

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-at-pembrolizumab-for-people-with-non-small-cell-lung-cancer-peps2

Study website

Contact information

Mr Rhys Mant
Public

CRUK Clinical Trials Unit
Institute of Cancer and Genomic Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom

Phone	+44 121 414 6788
Email	PePS2@trials.bham.ac.uk

Study information

Study design	Non-randomised; Interventional; Design type: Treatment, Screening, Diagnosis, Prevention, Drug, Imaging, Immunotherapy, Physical
Primary study design	Interventional
Secondary study design	Non randomised study
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
Scientific title	A phase II trial of pembrolizumab in patients with non-small cell lung cancer and a performance status of two
Study objectives	The aim of this study is to: 1. Determine that pembrolizumab is safe and tolerable at the selected dose 2. Detect the response rate, disease control rate and durability of these in this population of patients treated with pembrolizumab
Ethics approval(s)	West Midlands - Edgbaston Research Ethics Committee, 02/02/2016, ref: 16/WM/0010
Health condition(s) or problem(s) studied	Specialty: Cancer, Primary sub-specialty: Lung; UKCRC code/ Disease: Cancer/ Malignant neoplasms of respiratory and intrathoracic organs
Intervention	Pembrolizumab will be administered to all participants as a 30 minute IV infusion, at a flat dose of 200 mg, at a dosing interval of every 3 weeks for a maximum of 2 years. Follow up calls will be made every 4 weeks for 6 months then every 12 weeks to record treatment after progression and death date. Participants also undergo CT scanning every 9 weeks from baseline until disease progression, up to maximum of 2 years.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase II
Drug / device / biological / vaccine name(s)	Pembrolizumab
Primary outcome measure	1. Toxicity is measured by recording adverse events in relation to each cycle of treatment and grading according to CTCAE criteria continuously from baseline to 6 months post-treatment 2. Response rate is measured using CT scanning every 9 weeks from baseline until disease progression, up to maximum of 2 years
Secondary outcome measures	1. Best objective response rate (ORR) is measured using CT scanning every 9 weeks from baseline until disease progression, up to maximum of 2 years 2. Health related quality of life is measured using FACT-L Quality of Life Questionnaire at each treatment cycle i.e. every 3 weeks until study completion (up to a maximum of 2 years) 3. Time to Progression (TTP), defined as the time from commencement of trial treatment to the date of CT scan when progressive disease first recorded, is measured through CT scanning every 9 weeks from baseline until disease progression, up to maximum of 2 years 4. Progression-free survival time (PFS), defined as the time from commencement of trial treatment to the date of CT scan when progressive disease first recorded or date of death without previously recorded progression, is measured using RECIST 1.1 from baseline to up to maximum of 2 years 5. Overall survival time (OS), defined as the time from commencement of trial treatment to the date of death, is measured by patient survival until date of death 6. Duration of response (DoR), defined as the time from the CT scan when complete or partial response is first confirmed to the date of the subsequent CT scan when progressive disease is first confirmed or date of death without previously recorded progression, is calculated by RECIST 1.1 from baseline until disease progression, up to maximum of 2 years
Overall study start date	01/12/2015
Completion date	01/01/2022

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	Planned Sample Size: 60; UK Sample Size: 60
Total final enrolment	62
Key inclusion criteria	1. Patients must have completed all standard of care therapy that the treating oncologist deems appropriate. All lines of therapy will be allowed 2. Histologically confirmed NSCLC where it is possible to assess PD-L1 status on tumour biopsy. Biopsy must be within 70 days of first treatment with pembrolizumab. All patients who have had systemic therapy since the biopsy must have a repeat biopsy that is evaluable for PD-L1. 3. Patients must have a performance status of 2 on the ECOG Performance scale with no deterioration over the previous 2 weeks assessed by consenting physician 4. Life expectancy >12 weeks 5. Uni-dimensionally measurable disease according to RECIST version 1.1 6. CT scan of chest and abdomen within 28 days of starting Pembrolizumab demonstrating measurable disease as per RECIST version 1.1 7. Demonstrate adequate haematological and organ function as defined below. All screening tests should be performed within 7 days of treatment 8. Age 18 years and over 9. Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses 10. Patients must agree to the use of contraception as detailed in protocol and patient information sheet 11. System laboratory values: 11.1. Haematological Absolute neutrophil count ≥ 1.5 x 109/L Haemoglobin ≥ 90 g/L or ≥5.6 mmol/L Platelets ≥ 100 x 109/L 11.2. Hepatic function Total serum bilirubin ≤ 1.5 x ULN Alanine transferase (ALT) ≤ 2.5 x ULN. Aspartate transferase (AST) ≤ 2.5 x ULN. 11.3. Renal function Creatinine clearance <1.5 times ULN concurrent with creatinine clearance >50 ml/min (calculated by Cockcroft and Gault equation or alternative method). If this is ≤50 ml/min then an isotopic GFR may be undertaken and must be >50 ml/min.
Key exclusion criteria	1. Untreated symptomatic brain or leptomeningeal metastatic disease 2. Medical or psychiatric conditions comprising informed consent 3. Any medical condition which in the opinion of the investigator would compromise the ability of the patient to participate in the trial or which would jeopardise compliance with the protocol 4. Patient who has had chemotherapy, radioactive or biological cancer therapy within 4 weeks prior to the first dose of study therapy, or who has not recovered to CTCAE grade 1 or better from the adverse events due to cancer therapeutics administered more than 4 weeks earlier. Patient who has had erlotinib, gefitinib, afatinib, or crizotinib within 1 week prior to the first dose of study therapy, or who has not recovered to CTCAE Grade 1 or better from the adverse events due to any of these drugs administered more than 1 week earlier. Patient who has had ipilimumab therapy may be enrolled if requirements specified in Inclusion Criterion are met. 5. Active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. 6. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. 7. Patient has risk factors for bowel obstruction or bowel perforation (examples include but not limited to a history of acute diverticulitis, intra-abdominal abscess and abdominal carcinomatosis) 8. Patient has a known history of malignancy, unless the patient has undergone potentially curative therapy with no evidence of that disease for 5 years 9. Previous history of pneumonitis or significantly reduced transfer coefficient (KCO) 10. Female patients of child bearing potential should be using adequate contraceptive measures, should not be breast feeding and must have a negative pregnancy test prior to start of dosing 11. Patient previously had a severe hypersensitivity reaction to treatment with another monoclonal antibody 12. Patient had prior treatment targeting PD-1: PD-L1 axis or was previously randomized in any Pembrolizumab trial 13. Patient is positive for Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies), active Hepatitis B (HBsAg reactive) or Hepatitis C (HCV RNA (qualitative) is detected); patients with negative Hepatitis C antibody testing may not need RNA testing 14. Known history of tuberculosis 15. Patient has an active infection requiring therapy 16. Has received a live vaccine within 30 days prior to the first dose of trial treatment 17. Patient is, at the time of signing informed consent, a regular user (including “recreational use”) of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol) 18. Patients with symptomatic ascites or pleural effusion. A patient who is clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible
Date of first enrolment	30/09/2016
Date of final enrolment	13/02/2018

Locations

Countries of recruitment

England
United Kingdom
Wales

Study participating centres

University College London Hospital

1st Floor Central
250 Euston Road
London
NW1 2PG
United Kingdom

Southampton University Hospital

Tremona Road
Southampton
SO16 6YD
United Kingdom

Royal Marsden Hospital

Fulham Road
London
SW3 6JJ
United Kingdom

Barts Cancer Institute

Queen Mary University of London
Old Anatomy Building Basement
Room 2
Charterhouse Square
London
EC1M 6BQ
United Kingdom

The Christie NHS Foundation Trust

550 Wilmslow Road
Withington
Manchester
M20 4BX
United Kingdom

Maidstone Hospital

Hermitage Lane
Maidstone
ME16 9QQ
United Kingdom

Velindre Cancer Centre

Whitchurch
Cardiff
CF14 2TL
United Kingdom

Western General Hospital

Crewe Road South
Edinburgh
EH 4 2XU
United Kingdom

Queen Elizabeth Hospital

Mindelsohn Way
Birmingham
B15 2TH
United Kingdom

United Lincolnshire Hospitals NHS Trust

Lincoln
LN2 5QY
United Kingdom

Sponsor information

University of Birmingham
University/education

Vincent Drive
Edgbaston
Birmingham
B15 2TT
England
United Kingdom

"ROR"	https://ror.org/03angcq70

Funders

Funder type

Industry

Merck Sharp and Dohme
Private sector organisation / For-profit companies (industry)

Alternative name(s): MSD United Kingdom, Merck Sharp & Dohme, Merck Sharp & Dohme Corp., MSD
Location: United Kingdom

Results and Publications

Intention to publish date	19/03/2020
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
Publication and dissemination plan	Planned publication in a high-impact peer reviewed journal.
IPD sharing plan	Scientifically sound proposals from appropriately qualified researchers will be considered for data sharing. Requests should be made by returning a Data Sharing Request Form to newbusiness@trials.bham.ac.uk; this captures the research requirements, statistical analysis plan, and intended publication schedule. Requests will be reviewed by the Cancer Research UK Clinical Trials Unit (CRCTU) Directors in discussion with the Chief Investigator (CI), Trial Management Group (TMG) and independent Trial Steering Committee (TSC). They will consider the scientific validity of the request, qualifications of the researchers, CI, TMG & TSC views, consent arrangements, practicality of anonymizing the requested data & contractual obligations. If supportive of the request, and where not already obtained, Sponsor consent for data transfer will be sought before notifying applicants of the outcome. It is anticipated that applicants will be notified within 3 months of receipt of the original request.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/09/2020	23/03/2020	Yes	No
Plain English results			20/01/2021	No	Yes
HRA research summary			28/06/2023	No	No

Editorial Notes

06/02/2024: The following changes were made:
1. The individual participant data (IPD) sharing plan and summary were added.
2. The Publication and dissemination plan statement was added and the intention to publish date was changed from 01/09/2021 to 19/03/2020.
20/09/2021: Internal review.
20/01/2021: Cancer Research UK lay results summary link added to Results (plain English).
24/03/2020: The overall trial end date has been changed from 01/09/2020 to 01/01/2022.
23/03/2020: The following changes have been made:
1. Publication reference added.
2. The total final enrolment number has been added from the reference.
3. The ClinicalTrials.gov number has been added from the reference.
25/01/2019: The following changes have been made:
1. The recruitment end date has been changed from 01/09/2019 to 13/02/2018.
2. The trial website has been added.
3. The public contact has been changed from Dr Gillian McNab to Mr Rhys Mant.
4. Clatterbridge Cancer Centre and Freeman Hospital have been removed from the trial participating centres and Queen Elizabeth Hospital and United Lincolnshire Hospitals NHS Trust have been added.
01/11/2017: Internal review.
06/02/2017: Cancer Help UK lay summary link added to plain English summary field.