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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03924869




Registration number
NCT03924869
Ethics application status
Date submitted
22/04/2019
Date registered
23/04/2019
Date last updated
7/07/2020

Titles & IDs
Public title
Efficacy and Safety Study of Stereotactic Body Radiotherapy (SBRT) With or Without Pembrolizumab (MK-3475) in Adults With Medically Inoperable Stage I or IIA Non-Small Cell Lung Cancer (NSCLC) (MK-3475-867/KEYNOTE-867)
Scientific title
A Phase 3, Randomized, Placebo-Controlled Clinical Study to Evaluate the Safety and Efficacy of Stereotactic Body Radiotherapy (SBRT) With or Without Pembrolizumab (MK-3475) in Participants With Medically Inoperable Stages I or IIA Non Small Cell Lung Cancer (NSCLC) (KEYNOTE-867)
Secondary ID [1] 0 0
MK-3475-867
Secondary ID [2] 0 0
3475-867
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Stereotactic Body Radiotherapy (SBRT)
Other interventions - Pembrolizumab
Treatment: Drugs - Placebo

Experimental: SBRT+Pembolizumab - Participants receive SBRT once every 3 days for 3-5 fractions (dependent on tumor type/location; 45-54 Gray [Gy] total) over approximately 2 weeks PLUS pembrolizumab 200 mg via intravenous (IV) infusion once every 3 weeks for up to 17 cycles (up to approximately 1 year). Each cycle is 21 days.

Placebo Comparator: SBRT+Placebo - Participants receive SBRT once every 3 days for 3-5 fractions (dependent on tumor type/location; 45-54 Gy total) over approximately 2 weeks PLUS placebo (normal saline solution) via IV infusion once every 3 weeks for up to 17 cycles (up to approximately 1 year). Each cycle is 21 days.


Treatment: Other: Stereotactic Body Radiotherapy (SBRT)
SBRT

Other interventions: Pembrolizumab
IV infusion

Treatment: Drugs: Placebo
IV infusion

Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Other interventions
Intervention code [3] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Event-free Survival (EFS) - EFS is defined as the time from randomization to the first occurrence of any of the following events:
Local, regional, or distant recurrence of disease as assessed by:
Radiographic recurrence by blinded independent central review (BICR)
Positive pathology by local assessment
Physical examination by local assessment confirmed by positive pathology and/or radiographic recurrence by BICR OR
Death due to any cause. EFS will be presented.
Timepoint [1] 0 0
Up to approximately 6 years
Primary outcome [2] 0 0
Overall Survival (OS) - OS is defined as the time from date of randomization to date of death from any cause. OS will be presented.
Timepoint [2] 0 0
Up to approximately 6 years
Secondary outcome [1] 0 0
Time to Death or Distant Metastases (TDDM) - TTDM is defined as the time from randomization to the first documented distant metastases or death from any cause, whichever occurs first. The TDDM will be presented.
Timepoint [1] 0 0
Up to approximately 6 years
Secondary outcome [2] 0 0
Number of Participants Who Experience an Adverse Event (AE) - An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience an AE will be presented.
Timepoint [2] 0 0
Up to approximately 6 years
Secondary outcome [3] 0 0
Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) - An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinue study treatment due to an AE will be presented.
Timepoint [3] 0 0
Up to approximately 6 years
Secondary outcome [4] 0 0
Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Score - The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" are scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall outcome. The change from baseline in Global Health Status/Quality of Life (EORTC QLQ-C30 Items 29 and 30) combined score will be presented.
Timepoint [4] 0 0
Baseline and up to approximately 52 weeks
Secondary outcome [5] 0 0
Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer Module 13 (EORTC QLQ-LC13) Cough (Item 31) Score - The EORTC QLQ-LC13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30. Participant responses to the question "How much did you cough?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A lower score indicates a better outcome. The change from baseline in cough (EORTC QLQ LC13 Item 31) score will be presented.
Timepoint [5] 0 0
Baseline and up to approximately 52 weeks
Secondary outcome [6] 0 0
Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer Module 13 (EORTC QLQ-LC13) Chest Pain (Item 10) Score - The EORTC QLQ-LC13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30. Participant responses to the question "Have you had pain in your chest?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A lower score indicates a better outcome. The change from baseline in chest pain (EORTC QLQ-LC13 Item 40) score will be presented.
Timepoint [6] 0 0
Baseline and up to approximately 52 weeks
Secondary outcome [7] 0 0
Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Dyspnea (Item 8) Score - The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the question "Were you short of breath?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A lower score indicates a better outcome. The change from baseline in dyspnea (EORTC QLQ-C30 Item 8) score will be presented.
Timepoint [7] 0 0
Baseline and up to approximately 52 weeks
Secondary outcome [8] 0 0
Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) Physical Functioning (Items 1-5) Score - The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better quality of life. The change from baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) combined score will be presented.
Timepoint [8] 0 0
Baseline and up to approximately 52 weeks

Eligibility
Key inclusion criteria
- Has previously untreated NSCLC diagnosed by histology or cytology and confirmed as
Stage I or IIA NSCLC (American Joint Committee on Cancer, AJCC) by chest computed
tomography (CT) and positron emission tomography (PET) scan

- Cannot undergo thoracic surgery due to existing medical illness(es) as determined by
the site's multi-disciplinary tumor board

- Has a Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2

- Is able to receive SBRT and does not have an ultra-centrally located tumor

- Has adequate organ function within 7 days prior to the start of study treatment

- A female is eligible to participate if she is not pregnant, not breastfeeding, and at
least one of the following conditions applies: a) not a women of childbearing
potential (WOCBP) OR b) A WOCBP who agrees to use study-acceptable contraception
during treatment and for at least 120 days after last dose of study treatment
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Has received prior therapy with an anti-programmed cell death-1 (anti-PD-1),
anti-programmed cell death-ligand 1 (anti-PD-L1), or anti PD-L2 agent or with an agent
directed to another stimulatory or co-inhibitory T-cell receptor (e.g. cytotoxic
T-lymphocyte-associated antigen 4 [CTLA-4], tumor necrosis factor receptor superfamily
member 4 [OX-40], tumor necrosis factor receptor superfamily member 9 [CD137])

- Has received prior radiotherapy to the thorax, including radiotherapy to the
esophagus, mediastinum, or breast

- Has received a live vaccine within 30 days prior to the first dose of study treatment

- Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device within 4 weeks prior to the first dose of
study treatment. Note: Participants who have entered the follow-up phase of an
investigational study may participate as long as it has been 4 weeks after the last
dose of the previous investigational agent

- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior the first dose of study treatment

- Has a known additional malignancy that is progressing or has required active treatment
within the past 3 years. Note: Participants with basal cell carcinoma of the skin,
squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma,
cervical cancer in situ) that have undergone potentially curative therapy are not
excluded.

- Has a known hypersensitivity (=Grade 3) to pembrolizumab and/or any of its excipients

- Has a history of (non-infectious) pneumonitis that required steroids or has current
pneumonitis

- Has a known history of Hepatitis B or known active Hepatitis C virus infection

- Has an active autoimmune disease that has required systemic treatment in past 2 years
(i.e., with use of disease modifying agents, corticosteroids or immunosuppressive
drugs). However, replacement therapy (e.g. thyroxine, insulin, or physiologic
corticosteroid replacement therapy for adrenal or pituitary insufficiency), while
systemic, will be permitted for study eligibility.

- Has an active infection requiring systemic therapy

- Has a known history of human immunodeficiency virus (HIV) infection

- Has a known history of active tuberculosis (TB; Bacillus tuberculosis)

- Is pregnant or breastfeeding or expecting to conceive or father children within the
projected duration of the study, starting with the screening visit through 120 days
after the last dose of study treatment

- Has had an allogenic tissue/solid organ transplant

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Port Macquarie Base Hospital ( Site 2500) - Port Macquarie
Recruitment hospital [2] 0 0
Royal Brisbane and Women s Hospital ( Site 2502) - Herston
Recruitment hospital [3] 0 0
Austin Health ( Site 2501) - Melbourne
Recruitment postcode(s) [1] 0 0
2444 - Port Macquarie
Recruitment postcode(s) [2] 0 0
4029 - Herston
Recruitment postcode(s) [3] 0 0
3084 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Indiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Kentucky
Country [7] 0 0
United States of America
State/province [7] 0 0
Minnesota
Country [8] 0 0
United States of America
State/province [8] 0 0
New Jersey
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
North Dakota
Country [11] 0 0
United States of America
State/province [11] 0 0
Pennsylvania
Country [12] 0 0
United States of America
State/province [12] 0 0
South Dakota
Country [13] 0 0
United States of America
State/province [13] 0 0
Tennessee
Country [14] 0 0
United States of America
State/province [14] 0 0
Washington
Country [15] 0 0
Argentina
State/province [15] 0 0
Ciudad Autonoma De Buenos Aires
Country [16] 0 0
Argentina
State/province [16] 0 0
Santa Fe
Country [17] 0 0
Argentina
State/province [17] 0 0
Buenos Aires
Country [18] 0 0
Austria
State/province [18] 0 0
Oberosterreich
Country [19] 0 0
Austria
State/province [19] 0 0
Steiermark
Country [20] 0 0
Austria
State/province [20] 0 0
Tirol
Country [21] 0 0
Austria
State/province [21] 0 0
Wien
Country [22] 0 0
Brazil
State/province [22] 0 0
Rio Grande Do Sul
Country [23] 0 0
Brazil
State/province [23] 0 0
Sao Paulo
Country [24] 0 0
Brazil
State/province [24] 0 0
Rio de Janeiro
Country [25] 0 0
Canada
State/province [25] 0 0
New Brunswick
Country [26] 0 0
Canada
State/province [26] 0 0
Ontario
Country [27] 0 0
France
State/province [27] 0 0
Finistere
Country [28] 0 0
France
State/province [28] 0 0
Gironde
Country [29] 0 0
France
State/province [29] 0 0
Herault
Country [30] 0 0
France
State/province [30] 0 0
Seine-Maritime
Country [31] 0 0
France
State/province [31] 0 0
Vienne
Country [32] 0 0
France
State/province [32] 0 0
Paris
Country [33] 0 0
Germany
State/province [33] 0 0
Baden-Wurttemberg
Country [34] 0 0
Germany
State/province [34] 0 0
Niedersachsen
Country [35] 0 0
Germany
State/province [35] 0 0
Nordrhein-Westfalen
Country [36] 0 0
Germany
State/province [36] 0 0
Berlin
Country [37] 0 0
Hungary
State/province [37] 0 0
Borsod-Abauj-Zemplen
Country [38] 0 0
Hungary
State/province [38] 0 0
Gyor-Moson-Sopron
Country [39] 0 0
Hungary
State/province [39] 0 0
Jasz-Nagykun-Szolnok
Country [40] 0 0
Hungary
State/province [40] 0 0
Pest
Country [41] 0 0
Hungary
State/province [41] 0 0
Budapest
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Hungary
State/province [42] 0 0
Debrecen
Country [43] 0 0
Hungary
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Kaposvar
Country [44] 0 0
Italy
State/province [44] 0 0
Firenze
Country [45] 0 0
Italy
State/province [45] 0 0
Modena
Country [46] 0 0
Italy
State/province [46] 0 0
Roma
Country [47] 0 0
Japan
State/province [47] 0 0
Aichi
Country [48] 0 0
Japan
State/province [48] 0 0
Chiba
Country [49] 0 0
Japan
State/province [49] 0 0
Ibaraki
Country [50] 0 0
Japan
State/province [50] 0 0
Osaka
Country [51] 0 0
Japan
State/province [51] 0 0
Yamanashi
Country [52] 0 0
Japan
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Niigata
Country [53] 0 0
Japan
State/province [53] 0 0
Tokyo
Country [54] 0 0
Korea, Republic of
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Chungcheongbuk-do [Chungbuk]
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Korea, Republic of
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Kyonggi-do
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Korea, Republic of
State/province [56] 0 0
Seoul-teukbyeolsi [Seoul]
Country [57] 0 0
New Zealand
State/province [57] 0 0
Auckland
Country [58] 0 0
Norway
State/province [58] 0 0
Sor-Trondelag
Country [59] 0 0
Norway
State/province [59] 0 0
Vestfold
Country [60] 0 0
Norway
State/province [60] 0 0
Oslo
Country [61] 0 0
Poland
State/province [61] 0 0
Lodzkie
Country [62] 0 0
Poland
State/province [62] 0 0
Malopolskie
Country [63] 0 0
Poland
State/province [63] 0 0
Mazowieckie
Country [64] 0 0
Poland
State/province [64] 0 0
Slaskie
Country [65] 0 0
Poland
State/province [65] 0 0
Warminsko-mazurskie
Country [66] 0 0
Russian Federation
State/province [66] 0 0
Lipetskaya Oblast'
Country [67] 0 0
Russian Federation
State/province [67] 0 0
Sankt-Peterburg
Country [68] 0 0
Russian Federation
State/province [68] 0 0
Sverdlovskaya Oblast'
Country [69] 0 0
Russian Federation
State/province [69] 0 0
Tatarstan, Respublika
Country [70] 0 0
Spain
State/province [70] 0 0
Barcelona [Barcelona]
Country [71] 0 0
Spain
State/province [71] 0 0
Madrid
Country [72] 0 0
Spain
State/province [72] 0 0
Valenciana, Comunitat
Country [73] 0 0
Switzerland
State/province [73] 0 0
Geneve
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Switzerland
State/province [74] 0 0
Zurich
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Turkey
State/province [75] 0 0
Adana
Country [76] 0 0
Turkey
State/province [76] 0 0
Ankara
Country [77] 0 0
Turkey
State/province [77] 0 0
Istanbul
Country [78] 0 0
Turkey
State/province [78] 0 0
Izmir
Country [79] 0 0
Turkey
State/province [79] 0 0
Kayseri
Country [80] 0 0
Turkey
State/province [80] 0 0
Sakarya
Country [81] 0 0
Ukraine
State/province [81] 0 0
Dnipropetrovska Oblast
Country [82] 0 0
Ukraine
State/province [82] 0 0
Kharkivska Oblast
Country [83] 0 0
Ukraine
State/province [83] 0 0
Kirovohradska Oblast
Country [84] 0 0
Ukraine
State/province [84] 0 0
Kyivska Oblast
Country [85] 0 0
Ukraine
State/province [85] 0 0
Kyiv
Country [86] 0 0
United Kingdom
State/province [86] 0 0
Bristol, City Of
Country [87] 0 0
United Kingdom
State/province [87] 0 0
London, City Of
Country [88] 0 0
United Kingdom
State/province [88] 0 0
Norfolk
Country [89] 0 0
United Kingdom
State/province [89] 0 0
Darlington
Country [90] 0 0
United Kingdom
State/province [90] 0 0
Leicester
Country [91] 0 0
United Kingdom
State/province [91] 0 0
Northwood

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Merck Sharp & Dohme Corp.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to assess the efficacy and safety of stereotactic body
radiotherapy (SBRT) plus pembrolizumab (MK-3475) in the treatment of adult participants with
medically inoperable Stage I or IIA non-small cell lung cancer (NSCLC).

The primary study hypotheses are:

1. SBRT plus pembrolizumab prolongs Event-free Survival (EFS) compared to SBRT plus placebo
(normal saline solution), and

2. SBRT plus pembrolizumab prolongs Overall Survival (OS) compared to SBRT plus placebo.
Trial website
https://clinicaltrials.gov/show/NCT03924869
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme Corp.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Toll Free Number
Address 0 0
Country 0 0
Phone 0 0
1-888-577-8839
Fax 0 0
Email 0 0
Trialsites@merck.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03924869