Non-Small Cell Lung Cancer
Conditions
Keywords
Programmed Cell Death-1 (PD1, PD-1), Programmed Death-Ligand 1 (PDL1, PD-L1), Programmed Cell Death Receptor Ligand 2 (PDL2, PD-L2)
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 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).
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.
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).
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).
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event-free Survival (EFS) | Up to approximately 56.8 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Death or Distant Metastases (TDDM) | Up to approximately 56.8 months | 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. |
| Number of Participants Who Experienced an Adverse Event (AE) | Up to approximately 64 months | 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. |
| Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) | Up to approximately 16 months | 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. |
| 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 | Baseline and up to 24 weeks | 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. |
| Overall Survival (OS) | Up to approximately 56.8 months | OS was defined as the time from date of randomization to date of death from any cause. OS was reported for each arm. |
| 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 | Baseline and up to 24 weeks | 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. |
| 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 | Baseline and up to 24 weeks | 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. |
| 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 | Baseline and up to 24 weeks | 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. |
| 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 | Baseline and up to 24 weeks | 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. |
Countries
Argentina, Australia, Austria, Brazil, Canada, France, Germany, Hungary, Italy, Japan, Netherlands, New Zealand, Norway, Poland, Romania, Russia, South Korea, Spain, Switzerland, Taiwan, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Recruitment details
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.
Pre-assignment details
Of 737 participants screened, 448 were randomized 1:1 to receive either stereotactic body radiotherapy (SBRT) plus pembrolizumab or SBRT plus placebo.
Participants by arm
| Arm | Count |
|---|---|
| SBRT + Pembrolizumab Participants received 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 IV infusion once every 3 weeks for up to 17 cycles (up to approximately 1 year). Each cycle was 21 days. | 227 |
| SBRT + Placebo Participants received 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 was 21 days. | 221 |
| Total | 448 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 73 | 62 |
| Overall Study | Lost to Follow-up | 3 | 0 |
| Overall Study | Physician Decision | 0 | 3 |
| Overall Study | Study Terminated By Sponsor | 144 | 153 |
| Overall Study | Withdrawal by Subject | 7 | 3 |
Baseline characteristics
| Characteristic | SBRT + Pembrolizumab | SBRT + Placebo | Total |
|---|---|---|---|
| Age, Continuous | 73.2 years STANDARD_DEVIATION 8 | 72.4 years STANDARD_DEVIATION 7.6 | 72.8 years STANDARD_DEVIATION 7.8 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Score ECOG PS 0 = Normal activity | 86 Participants | 84 Participants | 170 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Score ECOG PS 1 = Symptoms, but ambulatory | 122 Participants | 122 Participants | 244 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Score ECOG PS 2 = Ambulatory, capable of selfcare, unable to carry out work activities | 19 Participants | 15 Participants | 34 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 23 Participants | 20 Participants | 43 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 190 Participants | 186 Participants | 376 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 14 Participants | 15 Participants | 29 Participants |
| Geographic Region of Enrollment Site East Asia | 29 Participants | 26 Participants | 55 Participants |
| Geographic Region of Enrollment Site Non-East Asia | 198 Participants | 195 Participants | 393 Participants |
| NSCLC Disease Stage Stage I | 204 Participants | 197 Participants | 401 Participants |
| NSCLC Disease Stage Stage II | 23 Participants | 24 Participants | 47 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 31 Participants | 26 Participants | 57 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 6 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 9 Participants | 9 Participants | 18 Participants |
| Race (NIH/OMB) White | 183 Participants | 177 Participants | 360 Participants |
| Reason for not Receiving Surgery Medically Inoperable | 184 Participants | 185 Participants | 369 Participants |
| Reason for not Receiving Surgery Refused Surgery | 43 Participants | 36 Participants | 79 Participants |
| Sex: Female, Male Female | 89 Participants | 100 Participants | 189 Participants |
| Sex: Female, Male Male | 138 Participants | 121 Participants | 259 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 76 / 227 | 63 / 221 |
| other Total, other adverse events | 198 / 226 | 176 / 218 |
| serious Total, serious adverse events | 90 / 226 | 74 / 218 |
Outcome results
Primary
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
Population: All randomized participants were analyzed according to the treatment arm they were randomized to.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SBRT + Pembrolizumab | Event-free Survival (EFS) | 31.2 months |
| SBRT + Placebo | Event-free Survival (EFS) | 28.3 months |
Comparison: Hazard ratio and 95% confidence intervals (CIs) were based on Cox regression model with Efron's method of tie handling with treatment as a covariate, stratified by Disease Stage (Stage I versus Stage II), ECOG Performance Status (0 or 1 versus 2), Geographic Region of Enrollment Site (East Asia versus non-East Asia), and Reason For Not Receiving Surgery (medically inoperable versus refused surgery).p-value: 0.293295% CI: [0.69, 1.24]Log Rank
Secondary
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
Population: All randomized participants who received at least 1 dose of study intervention and had at least 1 EORTC QLQ-C30 assessment available were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| SBRT + Pembrolizumab | 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 Score on a Scale |
| SBRT + 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 | -0.31 Score on a Scale |
Comparison: LS Mean change and 95% CIs were based on a cLDA model with the EORTC QLQ-C30 scores as the response variable with covariates for treatment by study visit interaction, and stratification factors by Disease Stage (Stage I versus Stage II), ECOG Performance Status (0 or 1 versus 2), Geographic Region of Enrollment Site (East Asia versus non-East Asia), and Reason For Not Receiving Surgery (medically inoperable versus refused surgery).p-value: 0.905595% CI: [-3.7, 3.28]cLDA model
Secondary
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
Population: All randomized participants who received at least 1 dose of study intervention and had at least 1 EORTC QLQ-C30 assessment available were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| SBRT + Pembrolizumab | 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 Score on a Scale |
| SBRT + 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 | -0.81 Score on a Scale |
Comparison: LS Mean change and 95% CIs were based on a cLDA model with the EORTC QLQ-C30 scores as the response variable with covariates for treatment by study visit interaction, and stratification factors by Disease Stage (Stage I versus Stage II), ECOG Performance Status (0 or 1 versus 2), Geographic Region of Enrollment Site (East Asia versus non-East Asia), and Reason For Not Receiving Surgery (medically inoperable versus refused surgery).p-value: 0.725395% CI: [-6.5, 4.53]cLDA model
Secondary
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
Population: All randomized participants who received at least 1 dose of study intervention and had at least 1 EORTC QLQ-C30 assessment available were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| SBRT + Pembrolizumab | 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 Score on a Scale |
| SBRT + 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 | -0.96 Score on a Scale |
Comparison: Stats:~LS Mean change and 95% CIs were based on a constrained longitudinal data analysis (cLDA) model with the EORTC QLQ-C30 scores as the response variable with covariates for treatment by study visit interaction, and stratification factors by Disease Stage (Stage I versus Stage II), ECOG Performance Status (0 or 1 versus 2), Geographic Region of Enrollment Site (East Asia versus non-East Asia), and Reason For Not Receiving Surgery (medically inoperable versus refused surgery).p-value: 0.518795% CI: [-4.9, 2.48]cLDA model
Secondary
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
Population: All randomized participants who received at least 1 dose of study intervention and had at least 1 EORTC QLQ-LC13 assessment available were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| SBRT + Pembrolizumab | 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 | 3.00 Score on a Scale |
| SBRT + 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) Score | 1.76 Score on a Scale |
Comparison: LS Mean change and 95% CIs were based on a cLDA model with the EORTC QLQ-LC13 scores as the response variable with covariates for treatment by study visit interaction, and stratification factors by Disease Stage (Stage I versus Stage II), ECOG Performance Status (0 or 1 versus 2), Geographic Region of Enrollment Site (East Asia versus non-East Asia), and Reason For Not Receiving Surgery (medically inoperable versus refused surgery).p-value: 0.548295% CI: [-2.83, 5.31]cLDA model
Secondary
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
Population: All randomized participants who received at least 1 dose of study intervention and had at least 1 EORTC QLQ-LC13 assessment available were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| SBRT + Pembrolizumab | 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 Score on a scale |
| SBRT + 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 | 2.91 Score on a scale |
Comparison: LS Mean change and 95% CIs were based on a cLDA model with the EORTC QLQ-LC13 scores as the response variable with covariates for treatment by study visit interaction, and stratification factors by Disease Stage (Stage I versus Stage II), ECOG Performance Status (0 or 1 versus 2), Geographic Region of Enrollment Site (East Asia versus non-East Asia), and Reason For Not Receiving Surgery (medically inoperable versus refused surgery).p-value: 0.090695% CI: [-9.38, 0.69]cLDA model
Secondary
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
Population: The analysis population consisted of all participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SBRT + Pembrolizumab | Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) | 62 Participants |
| SBRT + Placebo | Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) | 25 Participants |
Secondary
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
Population: The analysis population consisted of all participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SBRT + Pembrolizumab | Number of Participants Who Experienced an Adverse Event (AE) | 217 Participants |
| SBRT + Placebo | Number of Participants Who Experienced an Adverse Event (AE) | 200 Participants |
Secondary
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
Population: All randomized participants were analyzed according to the treatment arm they were randomized to.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SBRT + Pembrolizumab | Overall Survival (OS) | 54.7 months |
| SBRT + Placebo | Overall Survival (OS) | NA months |
Comparison: Hazard ratio and 95% CIs were based on Cox regression model with Efron's method of tie handling with treatment as a covariate, stratified by Disease Stage (Stage I versus Stage II), ECOG Performance Status (0 or 1 versus 2), Geographic Region of Enrollment Site (East Asia versus non-East Asia), and Reason for Not Receiving Surgery (medically inoperable versus refused surgery).p-value: 0.9397195% CI: [0.93, 1.9]Log Rank
Secondary
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
Population: All randomized participants were analyzed according to the treatment arm they were randomized to.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SBRT + Pembrolizumab | Time to Death or Distant Metastases (TDDM) | 39.1 months |
| SBRT + Placebo | Time to Death or Distant Metastases (TDDM) | 41.3 months |
Comparison: Hazard ratio and 95% CIs were based on Cox regression model with Efron's method of tie handling with treatment as a covariate, stratified by Disease Stage (Stage I versus Stage II), ECOG Performance Status (0 or 1 versus 2), Geographic Region of Enrollment Site (East Asia versus non-East Asia), and Reason for Not Receiving Surgery (medically inoperable versus refused surgery).95% CI: [0.74, 1.42]