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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)

NCT03924869

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief 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)
  • Official 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)

Clinical Trial IDs

  • ORG STUDY ID: 3475-867
  • SECONDARY ID: MK-3475-867
  • SECONDARY ID: 2018-004320-11
  • SECONDARY ID: KEYNOTE-867
  • NCT ID: NCT03924869

Conditions

  • Non-Small Cell Lung Cancer

Interventions

DrugSynonymsArms
PembrolizumabMK-3475, KEYTRUDA®SBRT+Pembolizumab
PlaceboNormal saline solutionSBRT+Placebo

Purpose

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 Arms

NameTypeDescriptionInterventions
SBRT+PembolizumabExperimentalParticipants 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.
  • Pembrolizumab
SBRT+PlaceboPlacebo ComparatorParticipants 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.
  • Placebo

Eligibility Criteria

        Inclusion Criteria:

          -  Has 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 participant's treating physician in consultation with 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

          -  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 treatment (pembrolizumab)

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Event-free Survival (EFS)
Time Frame:Up to approximately 6 years
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Time to Death or Distant Metastases (TDDM)
Time Frame:Up to approximately 6 years
Safety Issue:
Description: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.
Measure:Number of Participants Who Experience an Adverse Event (AE)
Time Frame:Up to approximately 6 years
Safety Issue:
Description: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.
Measure:Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)
Time Frame:Up to approximately 6 years
Safety Issue:
Description: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.
Measure: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
Time Frame:Baseline and up to approximately 52 weeks
Safety Issue:
Description: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.
Measure: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
Time Frame:Baseline and up to approximately 52 weeks
Safety Issue:
Description: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.
Measure: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
Time Frame:Baseline and up to approximately 52 weeks
Safety Issue:
Description: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.
Measure: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
Time Frame:Baseline and up to approximately 52 weeks
Safety Issue:
Description: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.
Measure: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
Time Frame:Baseline and up to approximately 52 weeks
Safety Issue:
Description: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.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Merck Sharp & Dohme Corp.

Trial Keywords

  • Programmed Cell Death-1 (PD1, PD-1)
  • Programmed Death-Ligand 1 (PDL1, PD-L1)

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