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TerminatedNCT03924869Updated Dec 11, 2025Results posted

Efficacy and Safety Study of Stereotactic Body Radiotherapy (SBRT) With or Without Pembrolizumab (MK-3475) in Adults With Unresected Stage I or II Non-Small Cell Lung Cancer (NSCLC) (MK-3475-867/KEYNOTE-867)

A Phase 3 interventional study of Stereotactic Body Radiotherapy (SBRT) and Pembrolizumab in Non-Small Cell Lung Cancer, sponsored by Merck Sharp & Dohme LLC. Terminated at 194 sites in 24 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-12-11.

Sponsored by Merck Sharp & Dohme LLC (part of Merck & Co., Inc) · Phase 3, Interventional, and Treatment

Why this study was terminated
Terminated for business reasons
Phase
Phase 3
Study type
Interventional
Enrollment
448
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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 unresected Stage I or II (Stage IIB N0, M0) non-small cell lung cancer (NSCLC).

The primary study hypothesis is SBRT plus pembrolizumab prolongs Event-free Survival (EFS) compared to SBRT plus placebo (normal saline solution).

Read the detailed description

As of protocol amendment 8, the study was stopped due to an interim analysis that did not support the study primary and key secondary endpoints. All study participants stopped ongoing treatment with pembrolizumab/placebo, and must complete end of trial and safety follow-up visits.

02

Conditions studied

  • Non-Small Cell Lung Cancer

Keywords

  • Programmed Cell Death-1 (PD1, PD-1)
  • Programmed Death-Ligand 1 (PDL1, PD-L1)
  • Programmed Cell Death Receptor Ligand 2 (PDL2, PD-L2)
03

In context

Carcinoma, Non-Small-Cell Lung

6,491 studies on the registry are indexed under Carcinoma, Non-Small-Cell Lung; 1,633 are open to participants now.

This study's enrollment of 448 is above the median of 62 across 5,216 interventional studies indexed under Carcinoma, Non-Small-Cell Lung.

Browse Carcinoma, Non-Small-Cell Lung studies →

Lead sponsor

Merck Sharp & Dohme LLC is the lead sponsor of 2,114 studies on the registry; 132 are open to participants now.

Of its 489 completed or terminated interventional studies of FDA-regulated products, 362 (74%) have results posted.

Browse Merck Sharp & Dohme LLC studies →All Merck & Co., Inc studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Has previously untreated non-small cell lung cancer (NSCLC) diagnosed by histology or cytology and confirmed as Stage I or II (T1 to limited T3, N0, M0) NSCLC (American Joint Committee on Cancer, AJCC) by chest computed tomography (CT) and positron emission tomography (PET) scan. Participants with pericardium invasion, >2 nodules or 2 nodules that cannot be treated in one field (>2 cm apart and/or total planned target volume [PTV] >163 cc) and diaphragm elevation suggestive of phrenic nerve invasion are excluded
  • Cannot undergo thoracic surgery due to existing medical illness(es) as determined by the site's multi-disciplinary tumor board. Medically operable participants who decide to treat with stereotactic body radiotherapy (SBRT) as definitive therapy rather than surgery are also eligible, if patient's unwillingness to undergo surgical resection is clearly documented
  • 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 and uses contraceptive method that is highly effective (with a failure rate of \<1% per year), or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), during the intervention period and for at least 120 days after the last dose of pembrolizumab/placebo and 180 days after the last radiotherapy dose
  • Male participants are eligible to participate if they agree to the following during the intervention period and for at least 90 days after the last dose of radiotherapy: refrain from donating sperm plus either be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent or must agree to use contraception per study protocol, unless confirmed to be azoospermic
  • Has a radiation therapy plan approved by the central radiation therapy quality assurance vendor

Exclusion criteria

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 intervention
  • Has received an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention administration
  • 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. A prior NSCLC that occurred and was treated curatively at least 2 years prior to the date of the current diagnosis would be considered a separate primary lung cancer, and therefore an additional malignancy. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast c 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, except replacement therapy
  • 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 pembrolizumab/placebo and 180 days after the last radiotherapy dose
  • Have not adequately recovered from major surgery or have ongoing surgical complications
  • Has had an allogenic tissue/solid organ transplant
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
448 participants (actual)

Study arms

  • Experimental
    SBRT + Pembrolizumab

    Participants receive SBRT once every 3 days for 3, 4, 5, or 8 fractions (dependent on tumor type/location; 45-70 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.

    Radiation: Stereotactic Body Radiotherapy (SBRT) · Biological: Pembrolizumab

  • Placebo comparator
    SBRT + Placebo

    Participants receive SBRT once every 3 days for 3, 4, 5, or 8 fractions (dependent on tumor type/location; 45-70 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.

    Radiation: Stereotactic Body Radiotherapy (SBRT) · Drug: Placebo

Interventions

  • RadiationStereotactic Body Radiotherapy (SBRT)

    SBRT will be administered once every 3 days for 3, 4, 5, or 8 fractions (dependent on tumor type/location; 45-70 Gray \[Gy\] total) over approximately 2 weeks.

  • BiologicalPembrolizumab

    Pembrolizumab will be administered at 200 mg via IV infusion once every 3 weeks for up to 17 cycles (up to approximately 1 year).

    Also known as: MK-3475, KEYTRUDA®

  • DrugPlacebo

    Placebo (normal saline solution) will be administered at 200 mg via IV infusion once every 3 weeks for up to 17 cycles (up to approximately 1 year).

06

What researchers measure

Primary outcomes

  1. Event-free Survival (EFS)

    EFS was defined as the time from randomization to the first occurrence of any of the following events: 1) 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 2) death due to any cause. EFS was reported for each arm.

    Time frame: Up to approximately 56.8 months

Secondary outcomes

  1. Overall Survival (OS)

    OS was defined as the time from date of randomization to date of death from any cause. OS was reported for each arm.

    Time frame: Up to approximately 56.8 months

  2. Time to Death or Distant Metastases (TDDM)

    TTDM was defined as the time from randomization to the first documented distant metastases or death from any cause, whichever occurred first. The TDDM was reported for each arm.

    Time frame: Up to approximately 56.8 months

  3. Number of Participants Who Experienced an Adverse Event (AE)

    An AE was defined as 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 experienced an AE were reported.

    Time frame: Up to approximately 64 months

  4. Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)

    An AE was defined as 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 discontinued study treatment due to an AE were reported.

    Time frame: Up to approximately 16 months

  5. 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?" were scored on a 7-point scale (1=Very Poor to 7=Excellent). The combined score of Global Health Status (EORTC QLQ-C30 Item 29) and Quality of Life (EORTC QLQ-C30 Item 30) was computed by averaging the raw scores of the 2 items and then applying a linear transformation to standardize the average score, so that the combined scores ranged from 0-100. A higher score indicates a better outcome. The change from baseline in GHS/QoL combined score was reported for each arm.

    Time frame: Baseline and up to 24 weeks

  6. 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-C30 is a questionnaire to assess the overall quality of life of cancer patients. The EORTC QLQ-LC13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30. Participant responses to the EORTC QLQ-LC13 question "How much did you cough?" were scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores were standardized, so that scores ranged from 0 to 100. A lower score indicates a better outcome. The change from baseline in cough (EORTC QLQ LC13 Item 31) score was reported for each arm.

    Time frame: Baseline and up to 24 weeks

  7. 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 40) Score

    The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. 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?" were scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores were standardized, so that scores ranged from 0 to 100. A lower score indicates a better outcome. The change from baseline in chest pain (EORTC QLQ-LC13 Item 40) score was reported for each arm.

    Time frame: Baseline and up to 24 weeks

  8. 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?" were scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores were standardized, so that scores ranged from 0 to 100. A lower score indicates a better outcome. The change from baseline in dyspnea (EORTC QLQ-C30 Item 8) score was reported for each arm.

    Time frame: Baseline and up to 24 weeks

  9. 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 were scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores were standardized, so that scores ranged 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 was reported for each arm.

    Time frame: Baseline and up to 24 weeks

07

Results

Posted May 11, 2025

Participant flow

Male and female participants at least 18 years of age with unresected Stage I or II (limited Stage IIB N0, M0) Non-Small Cell Lung Cancer (NSCLC) who had received no prior anticancer therapy for their present lung cancer were recruited.

Participant flow — Overall Study
MilestoneSBRT + PembrolizumabSBRT + Placebo
Started227221
Treated226218
Completed00
Not completed227221
Withdrew: Death7362
Withdrew: Lost to follow-up30
Withdrew: Physician decision03
Withdrew: Withdrawal by subject73
Withdrew: Study terminated by sponsor144153

Outcome measures

PrimaryEvent-free Survival (EFS)

EFS was defined as the time from randomization to the first occurrence of any of the following events: 1) 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 2) death due to any cause. EFS was reported for each arm.

Time frame:
Up to approximately 56.8 months
Reported as:
Median · months
Event-free Survival (EFS)
monthsSBRT + PembrolizumabSBRT + Placebo
Event-free Survival (EFS)31.2 (22.5 to 39.1)28.3 (19.8 to 33.1)
Statistical analysis
  • SBRT + Pembrolizumab vs SBRT + Placebo · Log Rank · p = 0.29320 (1-sided p-value based on log-rank test stratified by Disease Stage, ECOG Performance Status, Geographic Region of Enrollment Site, and Reason For Not Receiving Surgery.) · Hazard ratio (hr): 0.92 · 95% CI 0.69 to 1.24
SecondaryOverall Survival (OS)

OS was defined as the time from date of randomization to date of death from any cause. OS was reported for each arm.

Time frame:
Up to approximately 56.8 months
Reported as:
Median · months
Overall Survival (OS)
monthsSBRT + PembrolizumabSBRT + Placebo
Overall Survival (OS)54.7 (33.5 to NA)NA (44.4 to NA)
Statistical analysis
  • SBRT + Pembrolizumab vs SBRT + Placebo · Log Rank · p = 0.93971 (1-sided p-value based on log-rank test stratified by Disease Stage, ECOG Performance Status, Geographic Region of Enrollment Site, and Reason For Not Receiving Surgery.) · Hazard ratio (hr): 1.33 · 95% CI 0.93 to 1.90Per protocol, since the EFS null hypothesis was not rejected, the OS hypothesis was not formally tested and the p-value should be considered nominal.
SecondaryTime to Death or Distant Metastases (TDDM)

TTDM was defined as the time from randomization to the first documented distant metastases or death from any cause, whichever occurred first. The TDDM was reported for each arm.

Time frame:
Up to approximately 56.8 months
Reported as:
Median · months
Time to Death or Distant Metastases (TDDM)
monthsSBRT + PembrolizumabSBRT + Placebo
Time to Death or Distant Metastases (TDDM)39.1 (30.5 to NA)41.3 (31.1 to NA)
Statistical analysis
  • SBRT + Pembrolizumab vs SBRT + Placebo · Hazard ratio (hr): 1.02 · 95% CI 0.74 to 1.42
SecondaryNumber of Participants Who Experienced an Adverse Event (AE)

An AE was defined as 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 experienced an AE were reported.

Time frame:
Up to approximately 64 months
Reported as:
Count of participants · Participants
Number of Participants Who Experienced an Adverse Event (AE)
ParticipantsSBRT + PembrolizumabSBRT + Placebo
Number of Participants Who Experienced an Adverse Event (AE)217200
SecondaryNumber of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)

An AE was defined as 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 discontinued study treatment due to an AE were reported.

Time frame:
Up to approximately 16 months
Reported as:
Count of participants · Participants
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
ParticipantsSBRT + PembrolizumabSBRT + Placebo
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)6225
SecondaryChange 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?" were scored on a 7-point scale (1=Very Poor to 7=Excellent). The combined score of Global Health Status (EORTC QLQ-C30 Item 29) and Quality of Life (EORTC QLQ-C30 Item 30) was computed by averaging the raw scores of the 2 items and then applying a linear transformation to standardize the average score, so that the combined scores ranged from 0-100. A higher score indicates a better outcome. The change from baseline in GHS/QoL combined score was reported for each arm.

Time frame:
Baseline and up to 24 weeks
Reported as:
Least squares mean · Score on a Scale
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
Score on a ScaleSBRT + PembrolizumabSBRT + Placebo
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-2.17 (-5.00 to 0.66)-0.96 (-3.78 to 1.86)
Statistical analysis
  • SBRT + Pembrolizumab vs SBRT + Placebo · cLDA model · p = 0.5187 · Mean difference (final values): -1.21 · 95% CI -4.90 to 2.48
SecondaryChange 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-C30 is a questionnaire to assess the overall quality of life of cancer patients. The EORTC QLQ-LC13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30. Participant responses to the EORTC QLQ-LC13 question "How much did you cough?" were scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores were standardized, so that scores ranged from 0 to 100. A lower score indicates a better outcome. The change from baseline in cough (EORTC QLQ LC13 Item 31) score was reported for each arm.

Time frame:
Baseline and up to 24 weeks
Reported as:
Least squares mean · Score on a scale
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
Score on a scaleSBRT + PembrolizumabSBRT + Placebo
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-1.44 (-5.23 to 2.36)2.91 (-0.87 to 6.68)
Statistical analysis
  • SBRT + Pembrolizumab vs SBRT + Placebo · cLDA model · p = 0.0906 · Mean difference (final values): -4.34 · 95% CI -9.38 to 0.69
SecondaryChange 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 40) Score

The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. 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?" were scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores were standardized, so that scores ranged from 0 to 100. A lower score indicates a better outcome. The change from baseline in chest pain (EORTC QLQ-LC13 Item 40) score was reported for each arm.

Time frame:
Baseline and up to 24 weeks
Reported as:
Least squares mean · Score on a Scale
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 40) Score
Score on a ScaleSBRT + PembrolizumabSBRT + Placebo
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 40) Score3.00 (-0.09 to 6.10)1.76 (-1.32 to 4.84)
Statistical analysis
  • SBRT + Pembrolizumab vs SBRT + Placebo · cLDA model · p = 0.5482 · Mean difference (final values): 1.24 · 95% CI -2.83 to 5.31
SecondaryChange 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?" were scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores were standardized, so that scores ranged from 0 to 100. A lower score indicates a better outcome. The change from baseline in dyspnea (EORTC QLQ-C30 Item 8) score was reported for each arm.

Time frame:
Baseline and up to 24 weeks
Reported as:
Least squares mean · Score on a Scale
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
Score on a ScaleSBRT + PembrolizumabSBRT + Placebo
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-1.80 (-5.95 to 2.36)-0.81 (-4.94 to 3.32)
Statistical analysis
  • SBRT + Pembrolizumab vs SBRT + Placebo · cLDA model · p = 0.7253 · Mean difference (final values): -0.99 · 95% CI -6.50 to 4.53
SecondaryChange 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 were scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores were standardized, so that scores ranged 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 was reported for each arm.

Time frame:
Baseline and up to 24 weeks
Reported as:
Least squares mean · Score on a Scale
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
Score on a ScaleSBRT + PembrolizumabSBRT + Placebo
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-0.52 (-3.08 to 2.03)-0.31 (-2.86 to 2.24)
Statistical analysis
  • SBRT + Pembrolizumab vs SBRT + Placebo · cLDA model · p = 0.9055 · Mean difference (final values): -0.21 · 95% CI -3.70 to 3.28

Adverse events

Collected over Up to approximately 64 months. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Pembrolizumab + SBRT76/227 (33.5%)90/226 (39.8%)198/226 (87.6%)
Placebo + SBRT63/221 (28.5%)74/218 (33.9%)176/218 (80.7%)
Most frequent serious events
Showing 10 of 137
Most frequent serious events
EventPembrolizumab + SBRTPlacebo + SBRT
PneumoniaInfections and infestations19/2267/218
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders16/22610/218
PneumonitisRespiratory, thoracic and mediastinal disorders7/2261/218
COVID-19 pneumoniaInfections and infestations3/2266/218
Pneumonia bacterialInfections and infestations6/2262/218
Urinary tract infectionInfections and infestations6/2260/218
COVID-19Infections and infestations2/2265/218
AnaemiaBlood and lymphatic system disorders4/2261/218
Atrial fibrillationCardiac disorders4/2261/218
DyspnoeaRespiratory, thoracic and mediastinal disorders3/2263/218
Most frequent other events
Showing 10 of 37
Most frequent other events
EventPembrolizumab + SBRTPlacebo + SBRT
FatigueGeneral disorders51/22643/218
DyspnoeaRespiratory, thoracic and mediastinal disorders41/22639/218
CoughRespiratory, thoracic and mediastinal disorders34/22639/218
ArthralgiaMusculoskeletal and connective tissue disorders40/22616/218
PruritusSkin and subcutaneous tissue disorders39/22621/218
DiarrhoeaGastrointestinal disorders38/22631/218
HypothyroidismEndocrine disorders37/22610/218
RashSkin and subcutaneous tissue disorders36/22616/218
AnaemiaBlood and lymphatic system disorders28/22615/218
Decreased appetiteMetabolism and nutrition disorders26/22616/218

Baseline characteristics

Age, Continuous
Age, Continuous(years)SBRT + PembrolizumabSBRT + PlaceboTotal
Mean73.2 ± 8.072.4 ± 7.672.8 ± 7.8
Sex: Female, Male
Sex: Female, Male(Participants)SBRT + PembrolizumabSBRT + PlaceboTotal
Female89100189
Male138121259
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)SBRT + PembrolizumabSBRT + PlaceboTotal
Hispanic or Latino232043
Not Hispanic or Latino190186376
Unknown or Not Reported141529
Race (NIH/OMB)
Race (NIH/OMB)(Participants)SBRT + PembrolizumabSBRT + PlaceboTotal
American Indian or Alaska Native011
Asian312657
Native Hawaiian or Other Pacific Islander000
Black or African American4610
White183177360
More than one race022
Unknown or Not Reported9918
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Score
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Score(Participants)SBRT + PembrolizumabSBRT + PlaceboTotal
ECOG PS 0 = Normal activity8684170
ECOG PS 1 = Symptoms, but ambulatory122122244
ECOG PS 2 = Ambulatory, capable of selfcare, unable to carry out work activities191534
NSCLC Disease Stage
NSCLC Disease Stage(Participants)SBRT + PembrolizumabSBRT + PlaceboTotal
Stage I204197401
Stage II232447
Geographic Region of Enrollment Site
Geographic Region of Enrollment Site(Participants)SBRT + PembrolizumabSBRT + PlaceboTotal
East Asia292655
Non-East Asia198195393
Reason for not Receiving Surgery
Reason for not Receiving Surgery(Participants)SBRT + PembrolizumabSBRT + PlaceboTotal
Refused Surgery433679
Medically Inoperable184185369
08

Study locations

194 sites
  • University of Alabama ( Site 0099)
    Birmingham, Alabama 35233, United States
  • Infirmary Cancer Care ( Site 3044)
    Mobile, Alabama 36607, United States
  • Alaska Oncology and Hematology ( Site 3063)
    Anchorage, Alaska 99508, United States
  • Banner MD Anderson Cancer Center ( Site 3029)
    Gilbert, Arizona 85234, United States
  • CARTI Cancer Center ( Site 3045)
    Little Rock, Arkansas 72205, United States
  • USC Norris Comprehensive Cancer Center ( Site 0007)
    Los Angeles, California 90033, United States
  • Veterans Affairs Palo Alto Health Care System ( Site 3039)
    Palo Alto, California 94304, United States
  • National Jewish Health ( Site 0010)
    Denver, Colorado 80206, United States
  • Yale University ( Site 0011)
    New Haven, Connecticut 06510, United States
  • Mid Florida Hematology and Oncology Center ( Site 0067)
    Orange City, Florida 32763, United States
  • H. Lee Moffitt Cancer Center and Research Institute ( Site 0016)
    Tampa, Florida 33612, United States
  • Goshen Center for Cancer Care ( Site 0022)
    Goshen, Indiana 46526, United States
  • Franciscan Health Indianapolis ( Site 0024)
    Indianapolis, Indiana 46237, United States
  • University of Kentucky School of Medicine & Hospitals ( Site 0026)
    Lexington, Kentucky 40536, United States
  • Sinai Hospital of Baltimore ( Site 3011)
    Baltimore, Maryland 21215, United States
  • William E. Kahlert Regional Cancer Center ( Site 3031)
    Westminster, Maryland 21157, United States
  • Massachusetts General Hospital-Cancer Center Protocol Office ( Site 3007)
    Boston, Massachusetts 02114, United States
  • Mass General / North Shore Center for Outpatient Care ( Site 3040)
    Danvers, Massachusetts 01923, United States
  • University of Massachusetts ( Site 0029)
    Worcester, Massachusetts 01655, United States
  • Sanford Bemidji ( Site 0080)
    Bemidji, Minnesota 56601, United States
  • University of Minnesota ( Site 0069)
    Minneapolis, Minnesota 55455, United States
  • University of Missouri Hospital ( Site 3058)
    Columbia, Missouri 65212, United States
  • Cox Medical Center North-Cox Medical Center/Hulston Cancer Center/ Radiation Oncology ( Site 3060)
    Springfield, Missouri 65807, United States
  • St. Vincent Healthcare Frontier Cancer Center ( Site 3012)
    Billings, Montana 59102, United States
  • John Theurer Cancer Center at Hackensack University Medical Center ( Site 3036)
    Hackensack, New Jersey 07601, United States
  • Rutgers Cancer Institute of New Jersey ( Site 0043)
    New Brunswick, New Jersey 08903-2681, United States
  • Hematology-Oncology Associates of CNY ( Site 3055)
    East Syracuse, New York 13057, United States
  • Mount Sinai Hospital ( Site 0046)
    New York, New York 10029, United States
  • Westchester Medical Center ( Site 3057)
    Valhalla, New York 10595, United States
  • White Plains Hospital ( Site 3014)
    White Plains, New York 10601, United States
  • Sanford Health Roger Maris Cancer Center ( Site 0079)
    Fargo, North Dakota 58102, United States
  • Lehigh Valley Hospital- Cedar Crest ( Site 3005)
    Allentown, Pennsylvania 18103, United States
  • St. Luke's University Health Network ( Site 3006)
    Bethlehem, Pennsylvania 18015, United States
  • Penn State University Milton S. Hershey Medical Center ( Site 0064)
    Hershey, Pennsylvania 17033, United States
  • Fox Chase Cancer Center ( Site 0051)
    Philadelphia, Pennsylvania 19111, United States
  • Allegheny General Hospital ( Site 3028)
    Pittsburgh, Pennsylvania 15212, United States
  • Lankenau Medical Center ( Site 3041)
    Wynnewood, Pennsylvania 19096, United States
  • Sanford Cancer Center Oncology Clinic ( Site 0053)
    Sioux Falls, South Dakota 57104, United States
  • Mountain States Health Alliance ( Site 3054)
    Johnson City, Tennessee 37604, United States
  • University of Tennessee Medical Center Knoxville ( Site 3010)
    Knoxville, Tennessee 37920, United States
  • Vanderbilt University Medical Center ( Site 0075)
    Nashville, Tennessee 37232, United States
  • Cancer Care Northwest ( Site 0063)
    Spokane Valley, Washington 99216, United States
  • Hospital Italiano de Buenos Aires-Clinical Oncology ( Site 0206)
    ABB, Buenos Aires F.D. C1199ABB, Argentina
  • Hospital Britanico de Buenos Aires ( Site 0204)
    Buenos Aires, Buenos Aires F.D. C1280AEB, Argentina
  • Sanatorio Parque ( Site 0207)
    Rosario, Santa Fe Province S2000DSV, Argentina
  • Hospital Provincial del Centenario ( Site 0205)
    Rosario, Santa Fe Province S2002KDS, Argentina
  • IDIM Instituto de Diagnostico e Investigaciones Metabolicas ( Site 0208)
    Buenos Aires, 1012, Argentina
  • Hospital Aleman ( Site 0200)
    Buenos Aires, C1118AAT, Argentina
  • Instituto Medico Especializado Alexander Fleming ( Site 0203)
    Buenos Aires, C1426ANZ, Argentina
  • CEMIC ( Site 0201)
    Buenos Aires, C1431, Argentina
  • Port Macquarie Base Hospital ( Site 2500)
    Port Macquarie, New South Wales 2444, Australia
  • GenesisCare North Shore ( Site 2508)
    St Leonards, New South Wales 2065, Australia
  • Royal Brisbane and Women s Hospital ( Site 2502)
    Herston, Queensland 4029, Australia
  • Icon Cancer Centre Hobart ( Site 2507)
    Hobart, Tasmania 7000, Australia
  • Austin Health ( Site 2501)
    Melbourne, Victoria 3084, Australia
  • Social Medical Center - Otto Wagner Hospital ( Site 0801)
    Vienna, State of Vienna 1145, Austria
  • Landeskrankenhaus - Universitatsklinikum Graz ( Site 0804)
    Graz, Styria 8036, Austria
  • Universitatsklinik LKH Innsbruck ( Site 0802)
    Innsbruck, Tyrol 6020, Austria
  • Keppler Universitatsklinikum ( Site 0806)
    Linz, Upper Austria 4021, Austria
  • Irmandade da Santa Casa de Misericordia de Porto Alegre ( Site 0318)
    Porto Alegre, Rio Grande do Sul 90050-170, Brazil
  • Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 0301)
    Porto Alegre, Rio Grande do Sul 90610-000, Brazil
  • Clínica de Oncologia Reichow ( Site 0319)
    Blumenau, Santa Catarina 89010-340, Brazil
  • Hospital e Maternidade Celso Pierro ( Site 0313)
    Campinas, São Paulo 13060-904, Brazil
  • Instituto Nacional Do Cancer Jose Alencar Gomes Da Silva ( Site 0305)
    Rio de Janeiro, 20231-050, Brazil
  • Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 0300)
    São Paulo, 01246-000, Brazil
  • Hospital Paulistano - Amil Clinical Research ( Site 0316)
    São Paulo, 01321-001, Brazil
  • A.C. Camargo Cancer Center ( Site 0312)
    São Paulo, 01509-900, Brazil
  • Moncton Hospital - Horizon Health Network ( Site 0105)
    Moncton, New Brunswick E1C 6Z8, Canada
  • Health Sciences North Research Institute ( Site 0107)
    Greater Sudbury, Ontario P3E 5J1, Canada
  • Kingston Health Sciences Centre ( Site 0100)
    Kingston, Ontario K7L 2V7, Canada
  • Trillium Health Partners - Credit Valley Hospital ( Site 0102)
    Mississauga, Ontario L5M 2N1, Canada
  • The Ottawa Hospital ( Site 0104)
    Ottawa, Ontario K1H 8L6, Canada
  • Sault Area Hospital ( Site 0101)
    Sault Ste. Marie, Ontario P6B 0A8, Canada
  • CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont ( Site 0110)
    Montreal, Quebec H1T 2M4, Canada
  • McGill University Health Centre ( Site 0113)
    Montreal, Quebec H4A 3J1, Canada
  • CHUS - Hopital Fleurimont ( Site 0111)
    Sherbrooke, Quebec J1H 5N4, Canada
  • CHU Poitiers ( Site 1109)
    Poitiers, Ain 86021, France
  • CHU de Brest -Site Hopital Morvan ( Site 1100)
    Brest, Finistere 29200, France
  • Institut Bergonie ( Site 1102)
    Bordeaux, Gironde 33076, France
  • Institut Regional du Cancer de Montpellier - ICM ( Site 1108)
    Montpellier, Herault 34298, France
  • CHU de Rouen ( Site 1113)
    Rouen, Seine-Maritime 76000, France
  • Hopital Sud du Amiens ( Site 1115)
    Amiens, Somme 80054, France
  • Institut Curie ( Site 1112)
    Paris, 75005, France
  • Hopital Cochin ( Site 1107)
    Paris, 75014, France
  • A.P.H. Paris. Hopital Bichat Claude Bernard ( Site 1114)
    Paris, 75877, France
  • Klinikum Esslingen-Klinik für Kardiologie und Pneumologie ( Site 1208)
    Esslingen am Neckar, Baden-Wurttemberg 73730, Germany
  • Universitaetsklinikum Heidelberg. ( Site 1204)
    Heidelberg, Baden-Wurttemberg 69126, Germany
  • Universitaetsklinikum Erlangen ( Site 1209)
    Erlangen, Bavaria 91054, Germany
  • UKGM Gießen/Marburg-Medical Clinic V ( Site 1210)
    Giessen, Hesse 35392, Germany
  • Pius Hospital Oldenburg ( Site 1202)
    Oldenburg, Lower Saxony 26121, Germany
  • Universitaetsklinikum Essen ( Site 1201)
    Essen, North Rhine-Westphalia 45147, Germany
  • Evangelisches Krankenhaus Hamm gGmbH ( Site 1205)
    Hamm, North Rhine-Westphalia 59063, Germany
  • Charite Universitaetsmedizin Berlin ( Site 1207)
    Berlin, 13353, Germany
  • Pécsi Tudományegyetem Klinikai Központ-Onkoterápiás Intézet ( Site 2314)
    Pécs, Baranya 7624, Hungary
  • CRU Hungary KFT ( Site 2309)
    Miskolc, Borsod-Abauj Zemplen county 3529, Hungary
  • Bacs-Kiskun Varmegyei Oktatokorhaz-Onkoradiologiai Kozpont ( Site 2311)
    Kecskemét, Bács-Kiskun county 6000, Hungary
  • Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz ( Site 2312)
    Székesfehérvár, Fejér 8000, Hungary
  • Petz Aladar Megyei Oktato Korhaz ( Site 2305)
    Győr, Győr-Moson-Sopron 9024, Hungary
  • Debreceni Egyetem Klinikai Kozpont ( Site 2301)
    Debrecen, Hajdú-Bihar 4032, Hungary
  • Jász-Nagykun-Szolnok Vármegyei Hetényi Géza Kórház ( Site 2310)
    Szolnok, Jász-Nagykun-Szolnok 5004, Hungary

Showing the first 100 of 194 sites across 24 countries.

09

References and documents

Publications

  • Swaminath A, Parpia S, Wierzbicki M, Kundapur V, Faria S, Okawara GS, Tsakiridis TK, Ahmed N, Bujold A, Hirmiz K, Owen T, Leong N, Ramchandar K, Filion E, Lau H, Gabos Z, Thompson R, Yaremko B, Mehiri S, Louie AV, Quan K, Levine MN, Wright JR, Whelan TJ. Stereotactic vs Hypofractionated Radiotherapy for Inoperable Stage I Non-Small Cell Lung Cancer: The LUSTRE Phase 3 Randomized Clinical Trial. JAMA Oncol. 2024 Nov;10(11):1571-1575. doi: 10.1001/jamaoncol.2024.3089. Epub 2024 Sep 19. PubMed 39298144 ↗

Study documents

  • Protocol and statistical analysis plan · Oct 11, 2024

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Dec 11, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03924869
Lead sponsor
Merck Sharp & Dohme LLC
Responsible party
Sponsor
First posted
Apr 23, 2019
Start date
Jun 25, 2019
Primary completion
Jun 11, 2024
Completion
Jan 20, 2025
Results posted
May 11, 2025
Last update
Dec 11, 2025

Study contacts

Medical Director
study director · Merck Sharp & Dohme LLC

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is terminated, as verified in Nov 2025. You cannot join it, but the record below documents what was studied.

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Discussion

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