Carcinoma, Nonsquamous Non-small-cell Lung
Conditions
Keywords
Programmed Cell Death-1 (PD1, PD-1), Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1), Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)
Brief summary
The current study will compare pembrolizumab (MK-3475) plus maintenance olaparib, versus (vs) pembrolizumab plus maintenance pemetrexed for the treatment of non-squamous NSCLC. The study's 2 primary hypotheses are: 1. Pembrolizumab plus maintenance olaparib is superior to pembrolizumab plus maintenance pemetrexed with respect to progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by blinded independent clinical review (BICR) and 2. Pembrolizumab plus maintenance olaparib is superior to pembrolizumab plus maintenance pemetrexed with respect to overall survival (OS).
Detailed description
This study has 2 phases: an Induction Phase of up to \ 4 Cycles (up to \ 12 weeks \[cycle =3 weeks\]) and a Maintenance Phase of up to \ 31 cycles of pembrolizumab (cycle = 3 weeks\]); total pembrolizumab treatment duration will be up to \ 35 cycles (up to \ 2 years). In the Induction Phase, participants receive pembrolizumab plus pemetrexed plus platinum (carboplatin or cisplatin, at the investigator's discretion). 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 pemetrexed. In the Maintenance Phase, participants receive pembrolizumab for up to 31 cycles (cycle = 3 weeks) plus maintenance olaparib OR maintenance pemetrexed until progressive disease (PD), intolerable toxicities, or physician decision. Qualified participants in each study arm of the maintenance phase (Pembrolizumab plus Olaparib and Pembrolizumab plus Pemetrexed) who complete up to \ 35 cycles of pembrolizumab (up to \ 2 years \[cycle =3 weeks\]) may be eligible to receive a second course of pembrolizumab for up to \ 17 cycles (up to \ 1 additional year). Per protocol, response or progression during the second pembrolizumab course will not be counted towards patient reported outcomes (PROs) or efficacy outcome measures and adverse events during the second pembrolizumab course will not be counted towards safety outcome measures.
Interventions
BIOLOGICALPembrolizumab
IV infusion
DRUGPemetrexed
IV infusion
DRUGCarboplatin
IV infusion
DRUGCisplatin
IV infusion
DRUGOlaparib
Oral Tablet
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Have a histologically or cytologically confirmed diagnosis nonsquamous NSCLC. 2. Have stage IV nonsquamous NSCLC. 3. Have confirmation that epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), or Proto-oncogene tyrosine-protein kinase (ROS1)-directed therapy is not indicated. 4. Have measurable disease based on RECIST 1.1. 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 start the induction phase. 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 life expectancy of at least 3 months. 7. 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. 8. Have not received prior systemic treatment for their advanced/metastatic NSCLC. 9. Have adequate organ function. 10. 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. 11. Male participants must refrain from donating sperm, and female participants must refrain from donating eggs to others or freeze/store for her own use during the treatment period and for 180 days afterwards.
Exclusion criteria
1. Has predominantly squamous cell 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 (CNS) metastases and/or carcinomatous meningitis. 4. Has a severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients. 5. Has a known hypersensitivity to any components or excipients of cisplatin, carboplatin, pemetrexed, or olaparib. 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. 13. Has history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years. 14. Has completed palliative radiotherapy within 7 days of the first dose. Participants must have recovered from all radiation-related toxicities and not require corticosteroids.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | Up to ~31 months | PFS was defined as the time from randomization to the first documented progressive disease (PD) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) based on blinded independent central review (BICR) or death due to any cause, whichever occurs first. 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 also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. PFS was analyzed by the non-parametric Kaplan-Meier (K-M) method. The protocol specified final analysis of PFS is presented here for the first pembrolizumab course in the Maintenance Phase. Per protocol, analysis for this outcome measure was not planned or conducted in the Induction Phase. |
| Overall Survival (OS) | Up to ~51 months | OS was defined as the time from randomization to death due to any cause. OS was analyzed by the non-parametric K-M method. Participants without documented death at the time of analyses were censored at the date of last known to be alive. The protocol specified final analysis of OS is presented here for the first pembrolizumab course in the Maintenance Phase. Per protocol, analysis for this outcome measure was not planned or conducted in the Induction Phase. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experience One or More Adverse Events (AEs) | Up to ~5 years | An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience one or more AEs will be reported. The protocol specified final analysis will be presented for the first pembrolizumab course. |
| Number of Participants Who Discontinue Study Treatment Due to an AE | Up to ~5 years | An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinue study treatment due to an AE will be reported. The protocol specified final analysis will be presented for the first pembrolizumab course. |
| Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status / Quality of Life (Items 29 and 30) Scale Score | Baseline and Week 24 | EORTC QLQ-C30 is a questionnaire to assess the overall quality of life (QoL) of cancer patients. Participant responses to questions regarding Global Health Status (GHS; "How would you rate your overall health during the past week?") and QoL ("How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1= Very poor to 7=Excellent). The combined score of GHS (Item 29) and QoL (Item 30) is 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 range from 0-100. A higher score indicates a better outcome. The change from baseline in GHS and QoL combined score is presented. The protocol specified final analysis for the first pembrolizumab course in the Maintenance Phase is reported. Per protocol, analysis for this outcome measure was not planned or conducted in the Induction Phase. |
| Time to True Deterioration (TTD) in EORTC QLQ-C30 Global Health Status / Quality of Life (Items 29 & 30) Scale Score | Up to ~24 months | EORTC QLQ-C30 is a questionnaire to assess QoL of cancer patients. Participant responses to questions on GHS ("How would you rate your overall health during the past week?") and QoL ("How would you rate your overall QoL during the past week?") are scored on a 7-point scale (1= Very poor to 7=Excellent). The combined score of GHS (Item 29) and QoL (Item 30) is computed by averaging raw scores of the 2 items and applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicates a better outcome. TTD is defined as the time from baseline to first onset of ≥10-point negative change (decrease) from baseline in GHS-QoL combined score. TTD estimated by non-parametric K-M method is presented here. A longer TTD indicates a better outcome. The protocol specified final analysis for the first pembrolizumab course in the Maintenance Phase is reported. Per protocol, analysis for this outcome was not done in the Induction Phase. |
| Change From Baseline in EORTC Quality of Life Questionnaire Lung Cancer Module 13 (QLQ-LC13) Cough (Item 1) Scale Score | Baseline and Week 24 | EORTC QLQ-LC13 is a lung cancer specific questionnaire. Participant responses to the question regarding cough (Item 1): "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 0-100. A lower score indicates a better outcome. The change from baseline in EORTC QLQ-LC13 cough (Item 1) score is presented. The protocol specified final analysis for the first pembrolizumab course in the Maintenance Phase is reported. Per protocol, analysis for this outcome measure was not planned or conducted in the Induction Phase. |
| TTD in EORTC QLQ-LC13 Cough (Item 1) Scale Score | Up to ~24 months | EORTC QLQ-LC13 is a lung cancer specific questionnaire. Participant responses to the question regarding cough (Item 1): "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 0-100. A lower score indicates a better outcome. TTD is defined as the time from baseline to first onset of ≥10-point negative change (decrease) from baseline in cough (Item 1). TTD estimated by non-parametric K-M method is presented here. A longer TTD indicates a better outcome. The protocol specified final analysis for the first pembrolizumab course in the Maintenance Phase is reported. Per protocol, analysis for this outcome measure was not planned or conducted in the Induction Phase. |
| Change From Baseline in EORTC QLQ-LC13 Chest Pain (Item 10) Scale Score | Baseline and Week 24 | EORTC QLQ-LC13 is a lung cancer specific questionnaire. Participant responses to the question regarding chest pain (Item 10): "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. The protocol specified final analysis for the first pembrolizumab course in the Maintenance Phase is reported. Per protocol, analysis for this outcome measure was not planned or conducted in the Induction Phase. |
| TTD in EORTC QLQ-LC13 Chest Pain (Item 10) Scale Score | Up to ~24 months | EORTC QLQ-LC13 is a lung cancer specific questionnaire. Participant responses to the question regarding chest pain (Item 10): "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 is defined as the time from baseline to first onset of ≥10-point negative change (decrease) from baseline in chest pain (Item 10). TTD estimated by non-parametric K-M method is presented here. A longer TTD indicates a better outcome. The protocol specified final analysis for the first pembrolizumab course in Maintenance Phase is reported. Per protocol, analysis for this outcome measure was not planned or conducted in the Induction Phase. |
| Change From Baseline in EORTC QLQ-C30 Dyspnea (Item 8) Scale Score | Baseline and Week 24 | EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participant responses to the question regarding dyspnea (Item 8): "Were you short of breath?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A lower score indicates a better outcome. The change from baseline in EORTC QLQ-C30 dyspnea (Item 8) score is presented. The protocol specified final analysis for the first pembrolizumab course in Maintenance Phase is reported. Per protocol, analysis for this outcome measure was not planned or conducted in the Induction Phase. |
| TTD in EORTC QLQ-C30 Dyspnea (Item 8) Scale Score | Up to ~24 months | EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participant responses to the question regarding dyspnea (Item 8): "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 is defined as the time from baseline to first onset of ≥10-point negative change (decrease) from baseline in dyspnea (Item 8). TTD estimated by non-parametric K-M method is presented here. A longer TTD indicates a better outcome. The protocol specified final analysis for the first pembrolizumab course in the Maintenance Phase is reported. Per protocol, analysis for this outcome measure was not planned or conducted in the Induction Phase. |
| Change From Baseline in EORTC QLQ-C30 Physical Functioning (Items 1 to 5) Scale Score | Baseline and Week 24 | EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participant responses to 5 questions about their physical functioning (Items 1 to 5) are scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score of items 1 to 5 is computed by averaging the raw scores of the 5 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicates a better outcome. The change from baseline in EORTC QLQ-C30 physical functioning (Items 1-5) combined score is presented. The protocol specified final analysis for the first pembrolizumab course in Maintenance Phase is reported. Per protocol, analysis for this outcome measure was not planned or conducted in the Induction Phase. |
| TTD in EORTC QLQ-C30 Physical Functioning (Items 1 to 5) Scale Score | Up to ~24 months | EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participant responses to 5 questions about their physical functioning (Items 1 to 5) are scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score of items 1 to 5 is computed by averaging the raw scores of the 5 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicates a better outcome. TTD is defined as the time from baseline to first onset of ≥10-point negative change (decrease) from baseline in physical functioning (Items 1 to 5). TTD estimated by non-parametric K-M method is presented here. A longer TTD indicates a better outcome. The protocol specified final analysis for the first pembrolizumab course in the Maintenance Phase is reported. Per protocol, analysis for this outcome measure was not planned or conducted in the Induction Phase. |
Countries
Argentina, Australia, Austria, Brazil, Canada, Colombia, France, Germany, Japan, 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
Per protocol, response or progression during the second pembrolizumab course were not counted towards patient reported outcomes (PROs) or efficacy outcome measures and adverse events during the second pembrolizumab course will not be counted towards safety outcome measures.
Participants by arm
| Arm | Count |
|---|---|
| Pembrolizumab + Pemetrexed + Platinum Therapy (Induction Phase) Participants received 4 cycles (up to \
12 weeks \[cycle = 3 weeks\]): pembrolizumab 200 mg intravenous (IV) on Day 1 of each cycle (cycles 1 through 4) PLUS pemetrexed 500 mg/m\^2 IV on Day 1 of each cycle (cycles 1 through 4) PLUS platinum chemotherapy, investigator's choice: carboplatin area under the curve (AUC) 5 mg/mL/min IV on Day 1 of each cycle (Cycles 1 through 4) OR cisplatin 75 mg/m\^2 IV on Day 1 of each cycle (Cycles 1 through 4). | 331 |
| Pembrolizumab + Olaparib (Maintenance Phase) Eligible participants with a complete/partial response or stable disease to treatment in the Induction Phase could enter Maintenance Phase. For the Maintenance Phase, participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle for up to 31 cycles PLUS maintenance oral olaparib 300 mg twice daily. In the Maintenance Phase, participants continued to receive maintenance olaparib until progressive disease or toxicity. Across both phases, participants could receive pembrolizumab for a total treatment duration of up to \
35 cycles (up to \
2 years \[cycle = 3 weeks\]). Qualified participants who completed up to \
35 cycles of pembrolizumab (up to \
2 years) may have been eligible to receive a second course of pembrolizumab at the same dose and schedule (200 mg on Day 1 of each 3-week cycle) for up to \
17 cycles (up to \
1 additional year). | 337 |
| Pembrolizumab + Pemetrexed (Maintenance Phase) Eligible participants with a complete/partial response or stable disease to treatment in the Induction Phase could enter the Maintenance Phase. For the Maintenance Phase, participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle for up to 31 cycles PLUS maintenance pemetrexed 500 mg/m\^2 IV on Day 1 of each 3-week cycle. In the Maintenance Phase, participants continued to receive maintenance pemetrexed until progressive disease or toxicity. Across both phases, participants could receive pembrolizumab for a total treatment duration of up to \
35 cycles (up to \
2 years \[cycle = 3 weeks\]). Qualified participants who completed up to \
35 cycles of pembrolizumab (up to \
2 years) may have been eligible to receive a second course of pembrolizumab at the same dose and schedule (200 mg on Day 1 of each 3-week cycle) for up to \
17 cycles (up to \
1 additional year). | 335 |
| Total | 1,003 |
Baseline characteristics
| Characteristic | Pembrolizumab + Pemetrexed + Platinum Therapy (Induction Phase) | Pembrolizumab + Olaparib (Maintenance Phase) | Pembrolizumab + Pemetrexed (Maintenance Phase) | Total |
|---|---|---|---|---|
| Age, Continuous | 63.3 Years STANDARD_DEVIATION 9.4 | 61.6 Years STANDARD_DEVIATION 8.6 | 61.8 Years STANDARD_DEVIATION 9.8 | 62.3 Years STANDARD_DEVIATION 9.3 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) at Baseline of Maintenance Phase Grade 0 | 0 Participants | 142 Participants | 135 Participants | 277 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) at Baseline of Maintenance Phase Grade 1 | 0 Participants | 195 Participants | 200 Participants | 395 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 59 Participants | 50 Participants | 67 Participants | 176 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 246 Participants | 263 Participants | 253 Participants | 762 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 26 Participants | 24 Participants | 15 Participants | 65 Participants |
| Programmed Cell Death Ligand 1 (PD-L1) Status at Baseline of Maintenance Phase Missing | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Programmed Cell Death Ligand 1 (PD-L1) Status at Baseline of Maintenance Phase Not Evaluable | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Programmed Cell Death Ligand 1 (PD-L1) Status at Baseline of Maintenance Phase TPS<50% | 0 Participants | 228 Participants | 223 Participants | 451 Participants |
| Programmed Cell Death Ligand 1 (PD-L1) Status at Baseline of Maintenance Phase TPS ≥50% | 0 Participants | 109 Participants | 110 Participants | 219 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 5 Participants | 4 Participants | 1 Participants | 10 Participants |
| Race (NIH/OMB) Asian | 56 Participants | 91 Participants | 72 Participants | 219 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 4 Participants | 8 Participants | 21 Participants |
| Race (NIH/OMB) More than one race | 11 Participants | 7 Participants | 9 Participants | 27 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 14 Participants | 11 Participants | 9 Participants | 34 Participants |
| Race (NIH/OMB) White | 236 Participants | 218 Participants | 234 Participants | 688 Participants |
| Response at Baseline of Maintenance Phase Complete Response (CR)/Partial Response (PR) | 0 Participants | 189 Participants | 192 Participants | 381 Participants |
| Response at Baseline of Maintenance Phase Stable Disease (SD) | 0 Participants | 148 Participants | 143 Participants | 291 Participants |
| Sex: Female, Male Female | 109 Participants | 110 Participants | 109 Participants | 328 Participants |
| Sex: Female, Male Male | 222 Participants | 227 Participants | 226 Participants | 675 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 | 116 / 1,003 | 233 / 337 | 233 / 335 | 0 / 7 | 2 / 13 |
| other Total, other adverse events | 872 / 1,003 | 298 / 337 | 289 / 332 | 2 / 7 | 9 / 13 |
| serious Total, serious adverse events | 235 / 1,003 | 118 / 337 | 125 / 332 | 0 / 7 | 1 / 13 |
Outcome results
Primary
Overall Survival (OS)
OS was defined as the time from randomization to death due to any cause. OS was analyzed by the non-parametric K-M method. Participants without documented death at the time of analyses were censored at the date of last known to be alive. The protocol specified final analysis of OS is presented here for the first pembrolizumab course in the Maintenance Phase. Per protocol, analysis for this outcome measure was not planned or conducted in the Induction Phase.
Time frame: Up to ~51 months
Population: All randomized participants in the Maintenance Phase. Per protocol, analysis for this outcome measure was not planned or conducted in the Induction Phase.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab + Olaparib (Maintenance Phase) | Overall Survival (OS) | 20.7 Months |
| Pembrolizumab + Pemetrexed (Maintenance Phase) | Overall Survival (OS) | 23.0 Months |
p-value: 0.664995% CI: [0.87, 1.25]Log Rank
Primary
Progression-free Survival (PFS)
PFS was defined as the time from randomization to the first documented progressive disease (PD) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) based on blinded independent central review (BICR) or death due to any cause, whichever occurs first. 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 also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. PFS was analyzed by the non-parametric Kaplan-Meier (K-M) method. The protocol specified final analysis of PFS is presented here for the first pembrolizumab course in the Maintenance Phase. Per protocol, analysis for this outcome measure was not planned or conducted in the Induction Phase.
Time frame: Up to ~31 months
Population: All randomized participants in the Maintenance Phase. Per protocol, analysis for this outcome measure was not planned or conducted in the Induction Phase.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab + Olaparib (Maintenance Phase) | Progression-free Survival (PFS) | 7.1 Months |
| Pembrolizumab + Pemetrexed (Maintenance Phase) | Progression-free Survival (PFS) | 8.3 Months |
p-value: 0.872195% CI: [0.92, 1.36]Log Rank
Secondary
Change From Baseline in EORTC QLQ-C30 Dyspnea (Item 8) Scale Score
EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participant responses to the question regarding dyspnea (Item 8): Were you short of breath? are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A lower score indicates a better outcome. The change from baseline in EORTC QLQ-C30 dyspnea (Item 8) score is presented. The protocol specified final analysis for the first pembrolizumab course in Maintenance Phase is reported. Per protocol, analysis for this outcome measure was not planned or conducted in the Induction Phase.
Time frame: Baseline and Week 24
Population: All randomized participants in the Maintenance Phase who received at least one dose of Maintenance Phase study treatment and had at least 1 PRO assessment available. Per protocol, analysis for this outcome measure was not planned or conducted in the Induction Phase.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pembrolizumab + Olaparib (Maintenance Phase) | Change From Baseline in EORTC QLQ-C30 Dyspnea (Item 8) Scale Score | -0.16 Scores on a scale |
| Pembrolizumab + Pemetrexed (Maintenance Phase) | Change From Baseline in EORTC QLQ-C30 Dyspnea (Item 8) Scale Score | 1.35 Scores on a scale |
p-value: 0.442295% CI: [-5.38, 2.35]t-test, 2 sided
Secondary
Change From Baseline in EORTC QLQ-C30 Physical Functioning (Items 1 to 5) Scale Score
EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participant responses to 5 questions about their physical functioning (Items 1 to 5) are scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score of items 1 to 5 is computed by averaging the raw scores of the 5 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicates a better outcome. The change from baseline in EORTC QLQ-C30 physical functioning (Items 1-5) combined score is presented. The protocol specified final analysis for the first pembrolizumab course in Maintenance Phase is reported. Per protocol, analysis for this outcome measure was not planned or conducted in the Induction Phase.
Time frame: Baseline and Week 24
Population: All randomized participants in the Maintenance Phase who received at least one dose of Maintenance Phase study treatment and had at least 1 PRO assessment available. Per protocol, analysis for this outcome measure was not planned or conducted in the Induction Phase.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pembrolizumab + Olaparib (Maintenance Phase) | Change From Baseline in EORTC QLQ-C30 Physical Functioning (Items 1 to 5) Scale Score | -2.79 Scores on a scale |
| Pembrolizumab + Pemetrexed (Maintenance Phase) | Change From Baseline in EORTC QLQ-C30 Physical Functioning (Items 1 to 5) Scale Score | -2.78 Scores on a scale |
p-value: 0.996295% CI: [-2.94, 2.93]t-test, 2 sided
Secondary
Change From Baseline in EORTC QLQ-LC13 Chest Pain (Item 10) Scale Score
EORTC QLQ-LC13 is a lung cancer specific questionnaire. Participant responses to the question regarding chest pain (Item 10): 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. The protocol specified final analysis for the first pembrolizumab course in the Maintenance Phase is reported. Per protocol, analysis for this outcome measure was not planned or conducted in the Induction Phase.
Time frame: Baseline and Week 24
Population: All randomized participants in the Maintenance Phase who received at least one dose of Maintenance Phase study treatment and had at least 1 PRO assessment available. Per protocol, analysis for this outcome measure was not planned or conducted in the Induction Phase.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pembrolizumab + Olaparib (Maintenance Phase) | Change From Baseline in EORTC QLQ-LC13 Chest Pain (Item 10) Scale Score | -0.82 Scores on a scale |
| Pembrolizumab + Pemetrexed (Maintenance Phase) | Change From Baseline in EORTC QLQ-LC13 Chest Pain (Item 10) Scale Score | -0.47 Scores on a scale |
p-value: 0.828595% CI: [-3.54, 2.83]t-test, 2 sided
Secondary
Change From Baseline in EORTC Quality of Life Questionnaire Lung Cancer Module 13 (QLQ-LC13) Cough (Item 1) Scale Score
EORTC QLQ-LC13 is a lung cancer specific questionnaire. Participant responses to the question regarding cough (Item 1): 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 0-100. A lower score indicates a better outcome. The change from baseline in EORTC QLQ-LC13 cough (Item 1) score is presented. The protocol specified final analysis for the first pembrolizumab course in the Maintenance Phase is reported. Per protocol, analysis for this outcome measure was not planned or conducted in the Induction Phase.
Time frame: Baseline and Week 24
Population: All randomized participants in the Maintenance Phase who received at least one dose of Maintenance Phase study treatment and had at least 1 PRO assessment available. Per protocol, analysis for this outcome measure was not planned or conducted in the Induction Phase.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pembrolizumab + Olaparib (Maintenance Phase) | Change From Baseline in EORTC Quality of Life Questionnaire Lung Cancer Module 13 (QLQ-LC13) Cough (Item 1) Scale Score | -1.98 Scores on a scale |
| Pembrolizumab + Pemetrexed (Maintenance Phase) | Change From Baseline in EORTC Quality of Life Questionnaire Lung Cancer Module 13 (QLQ-LC13) Cough (Item 1) Scale Score | -1.82 Scores on a scale |
p-value: 0.936495% CI: [-4.02, 3.71]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 / Quality of Life (Items 29 and 30) Scale Score
EORTC QLQ-C30 is a questionnaire to assess the overall quality of life (QoL) of cancer patients. Participant responses to questions regarding Global Health Status (GHS; How would you rate your overall health during the past week?) and QoL (How would you rate your overall quality of life during the past week?) are scored on a 7-point scale (1= Very poor to 7=Excellent). The combined score of GHS (Item 29) and QoL (Item 30) is 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 range from 0-100. A higher score indicates a better outcome. The change from baseline in GHS and QoL combined score is presented. The protocol specified final analysis for the first pembrolizumab course in the Maintenance Phase is reported. Per protocol, analysis for this outcome measure was not planned or conducted in the Induction Phase.
Time frame: Baseline and Week 24
Population: All randomized participants in the Maintenance Phase who received at least one dose of Maintenance Phase study treatment and had at least 1 patient reported outcome (PRO) assessment available. Per protocol, analysis for this outcome measure was not planned or conducted in the Induction Phase.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pembrolizumab + 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 / Quality of Life (Items 29 and 30) Scale Score | -5.34 Scores on a scale |
| Pembrolizumab + Pemetrexed (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 / Quality of Life (Items 29 and 30) Scale Score | -3.44 Scores on a scale |
p-value: 0.253395% CI: [-5.16, 1.36]t-test, 2 sided
Secondary
Number of Participants Who Discontinue Study Treatment Due to an AE
An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinue study treatment due to an AE will be reported. The protocol specified final analysis will be presented for the first pembrolizumab course.
Time frame: Up to ~5 years
Secondary
Number of Participants Who Experience One or More Adverse Events (AEs)
An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience one or more AEs will be reported. The protocol specified final analysis will be presented for the first pembrolizumab course.
Time frame: Up to ~5 years
Secondary
Time to True Deterioration (TTD) in EORTC QLQ-C30 Global Health Status / Quality of Life (Items 29 & 30) Scale Score
EORTC QLQ-C30 is a questionnaire to assess QoL of cancer patients. Participant responses to questions on GHS (How would you rate your overall health during the past week?) and QoL (How would you rate your overall QoL during the past week?) are scored on a 7-point scale (1= Very poor to 7=Excellent). The combined score of GHS (Item 29) and QoL (Item 30) is computed by averaging raw scores of the 2 items and applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicates a better outcome. TTD is defined as the time from baseline to first onset of ≥10-point negative change (decrease) from baseline in GHS-QoL combined score. TTD estimated by non-parametric K-M method is presented here. A longer TTD indicates a better outcome. The protocol specified final analysis for the first pembrolizumab course in the Maintenance Phase is reported. Per protocol, analysis for this outcome was not done in the Induction Phase.
Time frame: Up to ~24 months
Population: All randomized participants in the Maintenance Phase who received at least one dose of Maintenance Phase study treatment, had at least 1 PRO assessment and had data available for this EORTC QLQ-C30 outcome measure. Per protocol, analysis for this outcome was not planned or conducted in the Induction Phase.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab + Olaparib (Maintenance Phase) | Time to True Deterioration (TTD) in EORTC QLQ-C30 Global Health Status / Quality of Life (Items 29 & 30) Scale Score | 19.81 Months |
| Pembrolizumab + Pemetrexed (Maintenance Phase) | Time to True Deterioration (TTD) in EORTC QLQ-C30 Global Health Status / Quality of Life (Items 29 & 30) Scale Score | 17.28 Months |
p-value: 0.812595% CI: [0.76, 1.24]Log Rank
Secondary
TTD in EORTC QLQ-C30 Dyspnea (Item 8) Scale Score
EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participant responses to the question regarding dyspnea (Item 8): 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 is defined as the time from baseline to first onset of ≥10-point negative change (decrease) from baseline in dyspnea (Item 8). TTD estimated by non-parametric K-M method is presented here. A longer TTD indicates a better outcome. The protocol specified final analysis for the first pembrolizumab course in the Maintenance Phase is reported. Per protocol, analysis for this outcome measure was not planned or conducted in the Induction Phase.
Time frame: Up to ~24 months
Population: All randomized participants in the Maintenance Phase who received at least one dose of Maintenance Phase study treatment, had at least 1 PRO assessment and had data available for this EORTC QLQ-C30 outcome measure. Per protocol, analysis for this outcome was not planned or conducted in the Induction Phase.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab + Olaparib (Maintenance Phase) | TTD in EORTC QLQ-C30 Dyspnea (Item 8) Scale Score | NA Months |
| Pembrolizumab + Pemetrexed (Maintenance Phase) | TTD in EORTC QLQ-C30 Dyspnea (Item 8) Scale Score | NA Months |
p-value: 0.915695% CI: [0.74, 1.31]Log Rank
Secondary
TTD in EORTC QLQ-C30 Physical Functioning (Items 1 to 5) Scale Score
EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participant responses to 5 questions about their physical functioning (Items 1 to 5) are scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score of items 1 to 5 is computed by averaging the raw scores of the 5 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicates a better outcome. TTD is defined as the time from baseline to first onset of ≥10-point negative change (decrease) from baseline in physical functioning (Items 1 to 5). TTD estimated by non-parametric K-M method is presented here. A longer TTD indicates a better outcome. The protocol specified final analysis for the first pembrolizumab course in the Maintenance Phase is reported. Per protocol, analysis for this outcome measure was not planned or conducted in the Induction Phase.
Time frame: Up to ~24 months
Population: All randomized participants in the Maintenance Phase who received at least one dose of Maintenance Phase study treatment, had at least 1 PRO assessment and had data available for this EORTC QLQ-C30 outcome measure. Per protocol, analysis for this outcome was not planned or conducted in the Induction Phase.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab + Olaparib (Maintenance Phase) | TTD in EORTC QLQ-C30 Physical Functioning (Items 1 to 5) Scale Score | 20.96 Months |
| Pembrolizumab + Pemetrexed (Maintenance Phase) | TTD in EORTC QLQ-C30 Physical Functioning (Items 1 to 5) Scale Score | NA Months |
p-value: 0.551795% CI: [0.83, 1.4]Log Rank
Secondary
TTD in EORTC QLQ-LC13 Chest Pain (Item 10) Scale Score
EORTC QLQ-LC13 is a lung cancer specific questionnaire. Participant responses to the question regarding chest pain (Item 10): 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 is defined as the time from baseline to first onset of ≥10-point negative change (decrease) from baseline in chest pain (Item 10). TTD estimated by non-parametric K-M method is presented here. A longer TTD indicates a better outcome. The protocol specified final analysis for the first pembrolizumab course in Maintenance Phase is reported. Per protocol, analysis for this outcome measure was not planned or conducted in the Induction Phase.
Time frame: Up to ~24 months
Population: All randomized participants in the Maintenance Phase who received at least one dose of Maintenance Phase study treatment, had at least 1 PRO assessment and had EORTC QLQ-LC13 data available for this outcome measure. Per protocol, analysis for this outcome was not planned or conducted in the Induction Phase.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab + Olaparib (Maintenance Phase) | TTD in EORTC QLQ-LC13 Chest Pain (Item 10) Scale Score | NA Months |
| Pembrolizumab + Pemetrexed (Maintenance Phase) | TTD in EORTC QLQ-LC13 Chest Pain (Item 10) Scale Score | NA Months |
p-value: 0.627295% CI: [0.78, 1.51]Log Rank
Secondary
TTD in EORTC QLQ-LC13 Cough (Item 1) Scale Score
EORTC QLQ-LC13 is a lung cancer specific questionnaire. Participant responses to the question regarding cough (Item 1): 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 0-100. A lower score indicates a better outcome. TTD is defined as the time from baseline to first onset of ≥10-point negative change (decrease) from baseline in cough (Item 1). TTD estimated by non-parametric K-M method is presented here. A longer TTD indicates a better outcome. The protocol specified final analysis for the first pembrolizumab course in the Maintenance Phase is reported. Per protocol, analysis for this outcome measure was not planned or conducted in the Induction Phase.
Time frame: Up to ~24 months
Population: All randomized participants in the Maintenance Phase who received at least one dose of Maintenance Phase study treatment, had at least 1 PRO assessment and had data available for this EORTC QLQ-LC13 outcome measure. Per protocol, analysis for this outcome was not planned or conducted in the Induction Phase.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab + Olaparib (Maintenance Phase) | TTD in EORTC QLQ-LC13 Cough (Item 1) Scale Score | NA Months |
| Pembrolizumab + Pemetrexed (Maintenance Phase) | TTD in EORTC QLQ-LC13 Cough (Item 1) Scale Score | NA Months |
p-value: 0.378295% CI: [0.66, 1.17]Log Rank