Carcinoma, Squamous Cell, Non-small-cell Lung
Conditions
Keywords
PD-1, PD L1, PD L2
Brief summary
The current study will compare pembrolizumab (MK-3475) plus maintenance olaparib, vs. pembrolizumab plus maintenance olaparib placebo for the treatment of squamous NSCLC. The study's 2 primary hypotheses are: 1. Pembrolizumab plus maintenance olaparib is superior to pembrolizumab plus maintenance olaparib placebo with respect to progression-free survival (PFS) per RECIST 1.1 by blinded independent clinical review (BICR). 2. Pembrolizumab plus maintenance olaparib is superior to pembrolizumab plus maintenance olaparib placebo with respect to overall survival (OS). As of Amendment 07, there will be no further analyses for OS and patient-reported outcome assessments.
Detailed description
This study has 2 phases: an Induction Phase (4 Cycles) and a Maintenance Phase (Up to 31 cycles of pembrolizumab). In the Induction Phase, participants receive pembrolizumab plus carboplatin plus a taxane (paclitaxel or nab-paclitaxel). In the Maintenance Phase, participants with a partial or complete disease response or with stable disease after completing four cycles of induction therapy and who meet eligibility criteria will be randomly assigned to receive pembrolizumab plus maintenance olaparib OR pembrolizumab plus maintenance olaparib placebo. In the Maintenance Phase, participants randomly assigned to receive pembrolizumab for up to 31 cycles plus maintenance olaparib OR maintenance olaparib placebo until centrally verified progressive disease (PD), intolerable toxicities, or physician decision. As of Amendment 07, participants actively taking placebo will discontinue taking the placebo intervention and continue in the study.
Interventions
BIOLOGICALPembrolizumab
IV infusion
DRUGCarboplatin
IV infusion
DRUGPaclitaxel
IV infusion
DRUGNab-paclitaxel
IV infusion
DRUGOlaparib
Tablets
DRUGPlacebo
Placebo to olaparib, tablets
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Have a histologically or cytologically confirmed diagnosis squamous NSCLC. 2. Have Stage IV squamous NSCLC. 3. Have measurable disease based on RECIST 1.1. 4. Have not received prior systemic treatment for their advanced/metastatic NSCLC. 5. Have provided archival tumor tissue sample or newly obtained core or incisional biopsy of a tumor lesion not previously irradiated. Note: Adequacy of biopsy specimen for the above analyses must be confirmed by the central laboratory before the participant can receive study intervention(s). Submission of another tumor specimen may be required prior to enrolling the participant, if adequate tumor tissue was not provided the first time. 6. Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status assessed within 7 days prior to the administration of study intervention 7. Have a life expectancy of at least 3 months. 8. Has adequate organ function. 9. Male and female participants who are not pregnant and of childbearing potential must follow contraceptive guidance during the treatment period and for 180 days afterwards. 10. Male participants must refrain from donating sperm during the treatment period and for 180 days afterwards.
Exclusion criteria
1. Has non-squamous histology NSCLC. 2. Has a known additional malignancy that is progressing or has progressed within the past 3 years requiring active treatment. 3. Has known active central nervous system metastases and/or carcinomatous meningitis. 4. Has a known hypersensitivity to any components or excipients of carboplatin, paclitaxel or nab-paclitaxel, or olaparib. 5. Has a severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients. 6. Has an active autoimmune disease that has required systemic treatment in past 2 years. 7. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy. 8. Has a known history of human immunodeficiency virus (HIV) infection, a known history of hepatitis B infection, or known active hepatitis C virus infection. 9. Has interstitial lung disease, or history of pneumonitis requiring systemic steroids for treatment. 10. Has received prior therapy with olaparib or with any other polyadenosine 5' diphosphoribose (polyADP ribose) polymerization (PARP) inhibitor. 11. Has received prior therapy with an agent directed to programmed cell death ligand 1 (PD-L1), anti PD-L2, or directed to a stimulatory or co-inhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), OX-40, CD137). 12. Has myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with features suggestive of MDS/AML.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | Up to approximately 39 months | Progression-free Survival was defined as the time from the date of randomization until either documented disease progression or death due to any cause, whichever occurred first. Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, progressive disease (PD) was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must have also demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. PFS as assessed by Blinded Independent Central Review (BICR) per RECIST 1.1 is presented. PFS is reported based on the non-parametric Kaplan-Meier method. Per protocol this outcome measure was not planned for the Induction Phase. |
| Overall Survival (OS) | Up to approximately 46 months | Overall survival was the time from the date of randomization to death due to any cause. OS is reported based on the non-parametric Kaplan-Meier method. Per protocol this outcome measure was not planned for the Induction Phase. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With One or More Adverse Events (AEs) | Up to approximately 4 years | An adverse event (AE) was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study. The number of participants who reported 1 or more AEs is presented. Per protocol this outcome measure was not planned for the Induction Phase. |
| Number of Participants Who Discontinued Study Intervention Due to an AE | Up to approximately 4 years | An AE was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study. The number of participants who discontinued study intervention due to an AE is presented. Per protocol this outcome measure was not planned for the Induction Phase. |
| Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (GHS)/ Quality of Life (QoL) (Items 29 and 30) Combined Scale Score | Baseline and Week 24 | EORTC QLQ-C30 is a 30-item questionnaire developed to assess the QoL of cancer patients. Participant responses to the Global Health Status GHS question "How would you rate your overall health during the past week?" (Item 29) and the QoL question "How would you rate your overall quality of life during the past week?" (Item 30) were each scored on a 7-point scale (1=Very Poor to 7=Excellent), then summed. Summed raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. Change from baseline in EORTC QLQ-C30 Items 29 and 30 combined score was assessed using a constrained longitudinal data analysis (cLDA) model with the patient-reported outcome (PRO) score as the response variable, and treatment, time, treatment-by-time interaction, and clinical study stratification factors as covariates. Per protocol this outcome measure was not planned for the Induction Phase. |
| Time to True Deterioration (TTD) in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (GHS)/Quality of Life (QoL) (Items 29 and 30) Scale Score | Up to approximately 2 years | TTD is defined as the time from Baseline to the first onset of a ≥10-point negative change (decrease) from Baseline in GHS (EORTC QLQ-C30 Item 29) and QoL score (EORTC QLQ-C30 Item 30). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10- point negative change (decrease) from Baseline in GHS score, will be presented. A longer TTD indicates a better outcome. TTD is reported based on the non-parametric Kaplan-Meier method. Per protocol this outcome measure was not planned for the Induction Phase. |
| Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer Module 13 (QLQ-LC13) Cough (Item 1) Scale Score | Baseline and Week 24 | The EORTC QLQ-LC13 is a lung cancer specific supplemental questionnaire used in combination with the EORTC QLQ-C30 questionnaire. 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 EORTC QLQ-LC13 cough (Item 1) score is presented. Change from baseline score was assessed using a cLDA model with the PRO score as the response variable, and treatment, time, treatment-by-time interaction, and clinical study stratification factors as covariates. Per protocol this outcome measure was not planned for the Induction Phase. |
| Time to True Deterioration (TTD) in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer Module 13 (QLQ-LC13) Cough (Item 1) Scale Score | Up to approximately 2 years | The EORTC QLQ-LC13 is a lung cancer specific supplemental questionnaire used in combination with the EORTC QLQ-C30 questionnaire. 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. TTD was defined as the time from baseline (at randomization) to the first onset of a ≥10-point decrease with confirmation by the subsequent visit of a ≥10-point decrease in cough scale score. The TTD for cough (Item 1) is presented. TTD is reported based on the non-parametric Kaplan-Meier method. Per protocol this outcome measure was not planned for the Induction Phase. |
| Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer Module 13 (QLQ-LC13) Chest Pain (Item 10) Scale Score | Baseline and Week 24 | The EORTC QLQ-LC13 is a lung cancer specific supplemental questionnaire used in combination with the EORTC QLQ-C30 questionnaire. 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 EORTC QLQ-LC13 chest pain (Item 10) score is presented. Change from baseline score was assessed using a cLDA model with the PRO score as the response variable, and treatment, time, treatment-by-time interaction, and clinical study stratification factors as covariates. Per protocol this outcome measure was not planned for the Induction Phase. |
| Time to True Deterioration (TTD) in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer Module 13 (QLQ-LC13) Chest Pain (Item 10) Scale Score | Up to approximately 2 years | The EORTC QLQ-LC13 is a lung cancer specific supplemental questionnaire used in combination with the EORTC QLQ-C30 questionnaire. 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. TTD was defined as the time from baseline (at randomization) to the first onset of a ≥10-point decrease with confirmation by the subsequent visit of a ≥10-point decrease in chest pain scale score. The TTD for chest pain (Item 10) is presented. TTD is reported based on the non-parametric Kaplan-Meier method. Per protocol this outcome measure was not planned for the Induction Phase. |
| Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Dyspnea (Item 8) Scale Score | Baseline and Week 24 | The EORTC QLQ-C30 is a 30-item 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. The change from baseline in EORTC QLQ-C30 dyspnea (Item 8) score will be presented. A lower score indicates a better outcome. The change from baseline in EORTC QLQ-C30 dyspnea (Item 8) score is presented. Change from baseline score was assessed using a cLDA model with the PRO score as the response variable, and treatment, time, treatment-by-time interaction, and clinical study stratification factors as covariates. Per protocol this outcome measure was not planned for the Induction Phase. |
| Time to True Deterioration (TTD) in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Dyspnea (Item 8) Scale Score | Up to approximately 2 years | 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. TTD was defined as the time from baseline (at randomization) to the first onset of a ≥10-point decrease with confirmation by the subsequent visit of a ≥10-point decrease in Item 8 scale score. The TTD for dyspnea (Item 8) is presented. TTD is reported based on the non-parametric Kaplan-Meier method. Per protocol this outcome measure was not planned for the Induction Phase. |
| Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Physical Functioning (Items 1 to 5) Scale Score | Baseline and Week 24 | The EORTC QLQ-C30 is a 30-item 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) score is presented. Change from baseline score was assessed using a constrained longitudinal data analysis (cLDA) model with the patient-reported outcome (PRO) score as the response variable, and treatment, time, treatment-by-time interaction, and clinical study stratification factors as covariates. Per protocol this outcome measure was not planned for the Induction Phase. |
| Time to True Deterioration (TTD) in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Physical Functioning (Items 1 to 5) Scale Score | Up to approximately 2 years | 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. TTD was defined as the time from baseline (at randomization) to the first onset of a ≥10-point decrease with confirmation by the subsequent visit of a ≥10-point decrease in physical functioning Items 1 to 5 scale scores. The TTD for physical functioning (Item 1-5) is presented. TTD is reported based on the non-parametric Kaplan-Meier method. Per protocol this outcome measure was not planned for the Induction Phase. |
Countries
Argentina, Australia, Austria, Brazil, Canada, France, Germany, Japan, Mexico, New Zealand, Poland, Romania, Russia, South Korea, Spain, Taiwan, Turkey (Türkiye), Ukraine, United Kingdom, United States
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Participant flow
Pre-assignment details
Study consisted of an Induction, Maintenance and Posttreatment phase. For induction, eligible participants were enrolled to receive pembrolizumab and carboplatin plus paclitaxel or nab-paclitaxel. Participants who met additional criteria were randomized 1:1 into a maintenance phase to receive either pembrolizumab combined with olaparib or pembrolizumab combined with placebo. In the posttreatment phase, participants were either followed up or administered a second course of pembrolizumab.
Participants by arm
| Arm | Count |
|---|---|
| Pembrolizumab (Pembro) + Carboplatin + Paclitaxel or Nab-Paclitaxel (Induction Phase) Participants received Pembrolizumab 200 mg intravenously (IV) every 3 weeks (Q3W) on Day 1 of each 21-day cycle for 4 cycles PLUS Carboplatin Area Under Curve (AUC) 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles PLUS investigator's choice of either Paclitaxel (200 mg/m\^2 Q3W on Day 1 of each 21-day cycle for 4 cycles or Nab-paclitaxel (100 mg/m\^2 Q3W on Days 1, 8, 15 of each 21-day cycle for 4 cycles). Participants may then randomize to one of the blinded treatment arms. | 260 |
| Pembro + Olaparib (Maintenance Phase) This arm includes participants who randomized following completion of the induction period. After the induction period, participants received pembrolizumab IV on Day 1 of each 21-day for up to 31 cycles PLUS maintenance oral olaparib 300 mg twice daily. In the Maintenance Phase, the participant continued to receive maintenance olaparib until centrally verified progressive disease, physician decision or intolerable toxicity.
Participants treated with pembrolizumab who completed 35 cycles of pembrolizumab during the study with stable disease (SD), complete response (CR), or partial response (PR), and without a current adverse event (AE), may have been eligible for retreatment with up to an additional 17 cycles (approximately 1 year) of pembrolizumab if they experienced radiographic disease progression after stopping treatment in the Maintenance Phase. | 296 |
| Pembro + Placebo (Maintenance Phase) This arm includes participants who randomized following completion of the induction period. After the induction period, participants received pembrolizumab IV on Day 1 of each 21-day for up to 31 cycles PLUS matching maintenance olaparib placebo twice daily. In the Maintenance Phase, the participant continued to receive maintenance olaparib placebo until centrally verified progressive disease, physician decision or intolerable toxicity.
Participants treated with pembrolizumab who completed 35 cycles of pembrolizumab during the study with SD, CR, or PR, and without a current AE, may have been eligible for retreatment with up to an additional 17 cycles (approximately 1 year) of pembrolizumab if they experienced radiographic disease progression after stopping treatment in the Maintenance Phase. | 295 |
| Total | 851 |
Baseline characteristics
| Characteristic | Pembrolizumab (Pembro) + Carboplatin + Paclitaxel or Nab-Paclitaxel (Induction Phase) | Pembro + Olaparib (Maintenance Phase) | Pembro + Placebo (Maintenance Phase) | Total |
|---|---|---|---|---|
| Age, Continuous | 65.5 Years STANDARD_DEVIATION 8.6 | 64.2 Years STANDARD_DEVIATION 8.8 | 64.6 Years STANDARD_DEVIATION 7.8 | 64.4 Years STANDARD_DEVIATION 8.4 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Grade 0 | 0 Participants | 83 Participants | 82 Participants | 165 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Grade 1 | 0 Participants | 213 Participants | 213 Participants | 426 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 34 Participants | 47 Participants | 48 Participants | 129 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 211 Participants | 239 Participants | 235 Participants | 685 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 15 Participants | 10 Participants | 12 Participants | 37 Participants |
| Programmed Cell Death-Ligand 1 (PD-L1) Expression Level: Tumor Proportion Score (TPS) Missing | 4 Participants | 1 Participants | 0 Participants | 5 Participants |
| Programmed Cell Death-Ligand 1 (PD-L1) Expression Level: Tumor Proportion Score (TPS) Not Evaluable | 5 Participants | 2 Participants | 2 Participants | 9 Participants |
| Programmed Cell Death-Ligand 1 (PD-L1) Expression Level: Tumor Proportion Score (TPS) TPS≥50% | 64 Participants | 85 Participants | 85 Participants | 234 Participants |
| Programmed Cell Death-Ligand 1 (PD-L1) Expression Level: Tumor Proportion Score (TPS) Tumor Proportion Score (TPS)<50% | 187 Participants | 208 Participants | 208 Participants | 603 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 5 Participants | 9 Participants | 11 Participants | 25 Participants |
| Race (NIH/OMB) Asian | 76 Participants | 63 Participants | 51 Participants | 190 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 4 Participants | 3 Participants | 11 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 1 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 9 Participants | 5 Participants | 7 Participants | 21 Participants |
| Race (NIH/OMB) White | 164 Participants | 214 Participants | 219 Participants | 597 Participants |
| Response Complete Response (CR)l/Partial Response (PR) | 0 Participants | 211 Participants | 218 Participants | 429 Participants |
| Response Missing | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Response Progressive Disease (PD) | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Response Stable Disease (SD) | 0 Participants | 84 Participants | 76 Participants | 160 Participants |
| Sex: Female, Male Female | 55 Participants | 55 Participants | 60 Participants | 170 Participants |
| Sex: Female, Male Male | 205 Participants | 241 Participants | 235 Participants | 681 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 101 / 851 | 188 / 296 | 189 / 295 | 0 / 7 | 2 / 9 |
| other Total, other adverse events | 787 / 851 | 265 / 294 | 240 / 292 | 4 / 7 | 6 / 9 |
| serious Total, serious adverse events | 220 / 851 | 97 / 294 | 77 / 292 | 2 / 7 | 1 / 9 |
Outcome results
Primary
Overall Survival (OS)
Overall survival was the time from the date of randomization to death due to any cause. OS is reported based on the non-parametric Kaplan-Meier method. Per protocol this outcome measure was not planned for the Induction Phase.
Time frame: Up to approximately 46 months
Population: The analysis population consisted of all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembro + Olaparib (Maintenance Phase) | Overall Survival (OS) | 19.1 Months |
| Pembro + Placebo (Maintenance Phase) | Overall Survival (OS) | 18.6 Months |
p-value: 0.548195% CI: [0.83, 1.24]Log Rank
Primary
Progression-free Survival (PFS)
Progression-free Survival was defined as the time from the date of randomization until either documented disease progression or death due to any cause, whichever occurred first. Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, progressive disease (PD) was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must have also demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. PFS as assessed by Blinded Independent Central Review (BICR) per RECIST 1.1 is presented. PFS is reported based on the non-parametric Kaplan-Meier method. Per protocol this outcome measure was not planned for the Induction Phase.
Time frame: Up to approximately 39 months
Population: The analysis population consisted of all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembro + Olaparib (Maintenance Phase) | Progression-free Survival (PFS) | 8.3 Months |
| Pembro + Placebo (Maintenance Phase) | Progression-free Survival (PFS) | 5.4 Months |
p-value: 0.00495% CI: [0.63, 0.93]Log Rank
Secondary
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Dyspnea (Item 8) Scale Score
The EORTC QLQ-C30 is a 30-item 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. The change from baseline in EORTC QLQ-C30 dyspnea (Item 8) score will be presented. A lower score indicates a better outcome. The change from baseline in EORTC QLQ-C30 dyspnea (Item 8) score is presented. Change from baseline score was assessed using a cLDA model with the PRO score as the response variable, and treatment, time, treatment-by-time interaction, and clinical study stratification factors as covariates. Per protocol this outcome measure was not planned for the Induction Phase.
Time frame: Baseline and Week 24
Population: The analysis population consists of all randomized participants who had at least one PRO assessment available and had received at least one dose of study medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pembro + Olaparib (Maintenance Phase) | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Dyspnea (Item 8) Scale Score | -1.08 Score on a Scale |
| Pembro + Placebo (Maintenance Phase) | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Dyspnea (Item 8) Scale Score | -1.25 Score on a Scale |
p-value: 0.938195% CI: [-4.27, 4.62]t-test, 2 sided
Secondary
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (GHS)/ Quality of Life (QoL) (Items 29 and 30) Combined Scale Score
EORTC QLQ-C30 is a 30-item questionnaire developed to assess the QoL of cancer patients. Participant responses to the Global Health Status GHS question How would you rate your overall health during the past week? (Item 29) and the QoL question How would you rate your overall quality of life during the past week? (Item 30) were each scored on a 7-point scale (1=Very Poor to 7=Excellent), then summed. Summed raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. Change from baseline in EORTC QLQ-C30 Items 29 and 30 combined score was assessed using a constrained longitudinal data analysis (cLDA) model with the patient-reported outcome (PRO) score as the response variable, and treatment, time, treatment-by-time interaction, and clinical study stratification factors as covariates. Per protocol this outcome measure was not planned for the Induction Phase.
Time frame: Baseline and Week 24
Population: The analysis population consists of all randomized participants who had at least one PRO assessment available and had received at least one dose of study medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pembro + Olaparib (Maintenance Phase) | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (GHS)/ Quality of Life (QoL) (Items 29 and 30) Combined Scale Score | -1.24 Score on a Scale |
| Pembro + Placebo (Maintenance Phase) | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (GHS)/ Quality of Life (QoL) (Items 29 and 30) Combined Scale Score | -1.62 Score on a Scale |
p-value: 0.823895% CI: [-2.91, 3.66]t-test, 2 sided
Secondary
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Physical Functioning (Items 1 to 5) Scale Score
The EORTC QLQ-C30 is a 30-item 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) score is presented. Change from baseline score was assessed using a constrained longitudinal data analysis (cLDA) model with the patient-reported outcome (PRO) score as the response variable, and treatment, time, treatment-by-time interaction, and clinical study stratification factors as covariates. Per protocol this outcome measure was not planned for the Induction Phase.
Time frame: Baseline and Week 24
Population: The analysis population consists of all randomized participants who had at least one PRO assessment available and had received at least one dose of study medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pembro + Olaparib (Maintenance Phase) | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Physical Functioning (Items 1 to 5) Scale Score | -2.04 Score on Scale |
| Pembro + Placebo (Maintenance Phase) | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Physical Functioning (Items 1 to 5) Scale Score | 0.77 Score on Scale |
p-value: 0.08795% CI: [-6.02, 0.41]t-test, 2 sided
Secondary
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer Module 13 (QLQ-LC13) Chest Pain (Item 10) Scale Score
The EORTC QLQ-LC13 is a lung cancer specific supplemental questionnaire used in combination with the EORTC QLQ-C30 questionnaire. 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 EORTC QLQ-LC13 chest pain (Item 10) score is presented. Change from baseline score was assessed using a cLDA model with the PRO score as the response variable, and treatment, time, treatment-by-time interaction, and clinical study stratification factors as covariates. Per protocol this outcome measure was not planned for the Induction Phase.
Time frame: Baseline and Week 24
Population: The analysis population consists of all randomized participants who had at least one PRO assessment available and had received at least one dose of study medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pembro + Olaparib (Maintenance Phase) | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer Module 13 (QLQ-LC13) Chest Pain (Item 10) Scale Score | 6.35 Score on a Scale |
| Pembro + Placebo (Maintenance Phase) | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer Module 13 (QLQ-LC13) Chest Pain (Item 10) Scale Score | 2.52 Score on a Scale |
p-value: 0.024595% CI: [0.5, 7.16]t-test, 2 sided
Secondary
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer Module 13 (QLQ-LC13) Cough (Item 1) Scale Score
The EORTC QLQ-LC13 is a lung cancer specific supplemental questionnaire used in combination with the EORTC QLQ-C30 questionnaire. 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 EORTC QLQ-LC13 cough (Item 1) score is presented. Change from baseline score was assessed using a cLDA model with the PRO score as the response variable, and treatment, time, treatment-by-time interaction, and clinical study stratification factors as covariates. Per protocol this outcome measure was not planned for the Induction Phase.
Time frame: Baseline and Week 24
Population: The analysis population consists of all randomized participants who had at least one PRO assessment available and had received at least one dose of study medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pembro + Olaparib (Maintenance Phase) | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer Module 13 (QLQ-LC13) Cough (Item 1) Scale Score | 2.42 Score on a Scale |
| Pembro + Placebo (Maintenance Phase) | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer Module 13 (QLQ-LC13) Cough (Item 1) Scale Score | 0.74 Score on a Scale |
p-value: 0.468695% CI: [-2.87, 6.23]t-test, 2 sided
Secondary
Number of Participants Who Discontinued Study Intervention Due to an AE
An AE was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study. The number of participants who discontinued study intervention due to an AE is presented. Per protocol this outcome measure was not planned for the Induction Phase.
Time frame: Up to approximately 4 years
Secondary
Number of Participants With One or More Adverse Events (AEs)
An adverse event (AE) was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study. The number of participants who reported 1 or more AEs is presented. Per protocol this outcome measure was not planned for the Induction Phase.
Time frame: Up to approximately 4 years
Secondary
Time to True Deterioration (TTD) in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Dyspnea (Item 8) Scale 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. TTD was defined as the time from baseline (at randomization) to the first onset of a ≥10-point decrease with confirmation by the subsequent visit of a ≥10-point decrease in Item 8 scale score. The TTD for dyspnea (Item 8) is presented. TTD is reported based on the non-parametric Kaplan-Meier method. Per protocol this outcome measure was not planned for the Induction Phase.
Time frame: Up to approximately 2 years
Population: The analysis population consists of all randomized participants who had at least one PRO assessment available and had received at least one dose of study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembro + Olaparib (Maintenance Phase) | Time to True Deterioration (TTD) in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Dyspnea (Item 8) Scale Score | NA Months |
| Pembro + Placebo (Maintenance Phase) | Time to True Deterioration (TTD) in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Dyspnea (Item 8) Scale Score | NA Months |
p-value: 0.846495% CI: [0.72, 1.31]Log Rank
Secondary
Time to True Deterioration (TTD) in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (GHS)/Quality of Life (QoL) (Items 29 and 30) Scale Score
TTD is defined as the time from Baseline to the first onset of a ≥10-point negative change (decrease) from Baseline in GHS (EORTC QLQ-C30 Item 29) and QoL score (EORTC QLQ-C30 Item 30). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10- point negative change (decrease) from Baseline in GHS score, will be presented. A longer TTD indicates a better outcome. TTD is reported based on the non-parametric Kaplan-Meier method. Per protocol this outcome measure was not planned for the Induction Phase.
Time frame: Up to approximately 2 years
Population: The analysis population consists of all randomized participants who had at least one PRO assessment available and had received at least one dose of study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembro + Olaparib (Maintenance Phase) | Time to True Deterioration (TTD) in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (GHS)/Quality of Life (QoL) (Items 29 and 30) Scale Score | 29.08 Months |
| Pembro + Placebo (Maintenance Phase) | Time to True Deterioration (TTD) in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (GHS)/Quality of Life (QoL) (Items 29 and 30) Scale Score | 29.01 Months |
p-value: 0.308395% CI: [0.66, 1.14]Log Rank
Secondary
Time to True Deterioration (TTD) in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Physical Functioning (Items 1 to 5) Scale 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. TTD was defined as the time from baseline (at randomization) to the first onset of a ≥10-point decrease with confirmation by the subsequent visit of a ≥10-point decrease in physical functioning Items 1 to 5 scale scores. The TTD for physical functioning (Item 1-5) is presented. TTD is reported based on the non-parametric Kaplan-Meier method. Per protocol this outcome measure was not planned for the Induction Phase.
Time frame: Up to approximately 2 years
Population: The analysis population consists of all randomized participants who had at least one PRO assessment available and had received at least one dose of study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembro + Olaparib (Maintenance Phase) | Time to True Deterioration (TTD) in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Physical Functioning (Items 1 to 5) Scale Score | 22.80 Months |
| Pembro + Placebo (Maintenance Phase) | Time to True Deterioration (TTD) in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Physical Functioning (Items 1 to 5) Scale Score | NA Months |
p-value: 0.00295% CI: [1.18, 2.16]Log Rank
Secondary
Time to True Deterioration (TTD) in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer Module 13 (QLQ-LC13) Chest Pain (Item 10) Scale Score
The EORTC QLQ-LC13 is a lung cancer specific supplemental questionnaire used in combination with the EORTC QLQ-C30 questionnaire. 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. TTD was defined as the time from baseline (at randomization) to the first onset of a ≥10-point decrease with confirmation by the subsequent visit of a ≥10-point decrease in chest pain scale score. The TTD for chest pain (Item 10) is presented. TTD is reported based on the non-parametric Kaplan-Meier method. Per protocol this outcome measure was not planned for the Induction Phase.
Time frame: Up to approximately 2 years
Population: The analysis population consists of all randomized participants who had at least one PRO assessment available and had received at least one dose of study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembro + Olaparib (Maintenance Phase) | Time to True Deterioration (TTD) in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer Module 13 (QLQ-LC13) Chest Pain (Item 10) Scale Score | NA Months |
| Pembro + Placebo (Maintenance Phase) | Time to True Deterioration (TTD) in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer Module 13 (QLQ-LC13) Chest Pain (Item 10) Scale Score | NA Months |
p-value: 0.213395% CI: [0.88, 1.75]Log Rank
Secondary
Time to True Deterioration (TTD) in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer Module 13 (QLQ-LC13) Cough (Item 1) Scale Score
The EORTC QLQ-LC13 is a lung cancer specific supplemental questionnaire used in combination with the EORTC QLQ-C30 questionnaire. 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. TTD was defined as the time from baseline (at randomization) to the first onset of a ≥10-point decrease with confirmation by the subsequent visit of a ≥10-point decrease in cough scale score. The TTD for cough (Item 1) is presented. TTD is reported based on the non-parametric Kaplan-Meier method. Per protocol this outcome measure was not planned for the Induction Phase.
Time frame: Up to approximately 2 years
Population: The analysis population consists of all randomized participants who had at least one PRO assessment available and had received at least one dose of study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembro + Olaparib (Maintenance Phase) | Time to True Deterioration (TTD) in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer Module 13 (QLQ-LC13) Cough (Item 1) Scale Score | 24.18 Months |
| Pembro + Placebo (Maintenance Phase) | Time to True Deterioration (TTD) in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer Module 13 (QLQ-LC13) Cough (Item 1) Scale Score | NA Months |
p-value: 0.917495% CI: [0.76, 1.35]Log Rank