Study of Pembrolizumab With Maintenance Olaparib or Maintenance Pemetrexed in First-line (1L) Metastatic Nonsquamous Non-Small-Cell Lung Cancer (NSCLC) (MK-7339-006, KEYLYNK-006)
- Conditions
- Carcinoma, Nonsquamous Non-small-cell Lung
- Interventions
- Registration Number
- NCT03976323
- Lead Sponsor
- Merck Sharp & Dohme LLC
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 1003
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Have a histologically or cytologically confirmed diagnosis nonsquamous NSCLC.
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Have stage IV nonsquamous NSCLC.
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Have confirmation that epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), or Proto-oncogene tyrosine-protein kinase (ROS1)-directed therapy is not indicated.
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Have measurable disease based on RECIST 1.1.
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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.
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Have a life expectancy of at least 3 months.
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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.
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Have not received prior systemic treatment for their advanced/metastatic NSCLC.
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Have adequate organ function.
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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.
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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.
- Has predominantly squamous cell histology NSCLC.
- Has a known additional malignancy that is progressing or has progressed within the past 3 years requiring active treatment.
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- Has a severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
- Has a known hypersensitivity to any components or excipients of cisplatin, carboplatin, pemetrexed, or olaparib.
- Has an active autoimmune disease that has required systemic treatment in past 2 years.
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy.
- Has a known history of human immunodeficiency virus (HIV) infection, a known history of hepatitis B infection, or known active hepatitis C virus infection.
- Has interstitial lung disease, or history of pneumonitis requiring systemic steroids for treatment.
- Has received prior therapy with olaparib or with any other polyadenosine 5' diphosphoribose (polyADP ribose) polymerization (PARP) inhibitor.
- 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).
- Has myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with features suggestive of MDS/AML.
- Has history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years.
- Has completed palliative radiotherapy within 7 days of the first dose. Participants must have recovered from all radiation-related toxicities and not require corticosteroids.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Pembrolizumab + Pemetrexed + Platinum Therapy + Olaparib Pembrolizumab For the Induction Phase, participants receive 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). If the participant has a complete/partial response or stable disease to induction therapy, the participant can enter the Maintenance Phase and receive 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. The participant can continue to receive maintenance olaparib until progressive disease or toxicity. Across both phases, participants can receive pembrolizumab for a total treatment duration of up to \~35 cycles (up to \~2 years \[cycle = 3 weeks\]). Pembrolizumab + Pemetrexed + Platinum Therapy + Olaparib Pemetrexed For the Induction Phase, participants receive 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). If the participant has a complete/partial response or stable disease to induction therapy, the participant can enter the Maintenance Phase and receive 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. The participant can continue to receive maintenance olaparib until progressive disease or toxicity. Across both phases, participants can receive pembrolizumab for a total treatment duration of up to \~35 cycles (up to \~2 years \[cycle = 3 weeks\]). Pembrolizumab + Pemetrexed + Platinum Therapy + Olaparib Carboplatin For the Induction Phase, participants receive 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). If the participant has a complete/partial response or stable disease to induction therapy, the participant can enter the Maintenance Phase and receive 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. The participant can continue to receive maintenance olaparib until progressive disease or toxicity. Across both phases, participants can receive pembrolizumab for a total treatment duration of up to \~35 cycles (up to \~2 years \[cycle = 3 weeks\]). Pembrolizumab + Pemetrexed + Platinum Therapy + Olaparib Cisplatin For the Induction Phase, participants receive 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). If the participant has a complete/partial response or stable disease to induction therapy, the participant can enter the Maintenance Phase and receive 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. The participant can continue to receive maintenance olaparib until progressive disease or toxicity. Across both phases, participants can receive pembrolizumab for a total treatment duration of up to \~35 cycles (up to \~2 years \[cycle = 3 weeks\]). Pembrolizumab + Pemetrexed + Platinum Therapy + Olaparib Olaparib For the Induction Phase, participants receive 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). If the participant has a complete/partial response or stable disease to induction therapy, the participant can enter the Maintenance Phase and receive 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. The participant can continue to receive maintenance olaparib until progressive disease or toxicity. Across both phases, participants can receive pembrolizumab for a total treatment duration of up to \~35 cycles (up to \~2 years \[cycle = 3 weeks\]). Pembrolizumab + Pemetrexed + Platinum Therapy + Pemetrexed Pembrolizumab For the Induction Phase, participants receive 4 cycles (up to \~12 weeks \[cycle = 3 weeks\]): pembrolizumab 200 mg 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 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). If the participant has a complete/partial response or stable disease to induction therapy, the participant can enter the Maintenance Phase and receive 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. The participant can continue to receive maintenance pemetrexed until progressive disease or toxicity. Across both phases, participants can receive pembrolizumab for a total treatment duration of up to \~35 cycles (up to \~2 years \[cycle = 3 weeks\]). Pembrolizumab + Pemetrexed + Platinum Therapy + Pemetrexed Pemetrexed For the Induction Phase, participants receive 4 cycles (up to \~12 weeks \[cycle = 3 weeks\]): pembrolizumab 200 mg 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 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). If the participant has a complete/partial response or stable disease to induction therapy, the participant can enter the Maintenance Phase and receive 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. The participant can continue to receive maintenance pemetrexed until progressive disease or toxicity. Across both phases, participants can receive pembrolizumab for a total treatment duration of up to \~35 cycles (up to \~2 years \[cycle = 3 weeks\]). Pembrolizumab + Pemetrexed + Platinum Therapy + Pemetrexed Carboplatin For the Induction Phase, participants receive 4 cycles (up to \~12 weeks \[cycle = 3 weeks\]): pembrolizumab 200 mg 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 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). If the participant has a complete/partial response or stable disease to induction therapy, the participant can enter the Maintenance Phase and receive 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. The participant can continue to receive maintenance pemetrexed until progressive disease or toxicity. Across both phases, participants can receive pembrolizumab for a total treatment duration of up to \~35 cycles (up to \~2 years \[cycle = 3 weeks\]). Pembrolizumab + Pemetrexed + Platinum Therapy + Pemetrexed Cisplatin For the Induction Phase, participants receive 4 cycles (up to \~12 weeks \[cycle = 3 weeks\]): pembrolizumab 200 mg 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 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). If the participant has a complete/partial response or stable disease to induction therapy, the participant can enter the Maintenance Phase and receive 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. The participant can continue to receive maintenance pemetrexed until progressive disease or toxicity. Across both phases, participants can receive pembrolizumab for a total treatment duration of up to \~35 cycles (up to \~2 years \[cycle = 3 weeks\]).
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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.
Trial Locations
- Locations (178)
Renovatio Clinical ( Site 0062)
🇺🇸The Woodlands, Texas, United States
Liverpool Hospital ( Site 1201)
🇦🇺Liverpool, New South Wales, Australia
Stronach Regional Cancer Centre ( Site 0101)
🇨🇦Newmarket, Ontario, Canada
Przychodnia Lekarska Komed ( Site 2416)
🇵🇱Konin, Wielkopolskie, Poland
Medstar Good Samaritan Hospital ( Site 0040)
🇺🇸Baltimore, Maryland, United States
Hospital Tacchini ( Site 0208)
🇧🇷Bento Goncalves, Rio Grande Do Sul, Brazil
Grigoriev Institute for medical Radiology NAMS of Ukraine ( Site 2212)
🇺🇦Kharkiv, Kharkivska Oblast, Ukraine
Clinica Colsanitas S.A. Sede Clinica Universitaria Colombia ( Site 0601)
🇨🇴Bogota, Distrito Capital De Bogota, Colombia
S.C. Radiotherapy Center Cluj S.R.L ( Site 2507)
🇷🇴Cluj-Napoca, Cluj, Romania
Spitalul Clinic Judetean De Urgenta Constanta ( Site 2501)
🇷🇴Constanta, Romania
City Clinical Hosp.4 of DCC ( Site 2201)
🇺🇦Dnipro, Dnipropetrovska Oblast, Ukraine
Medical and Diagnostic Centre LLC Dobryi Prognoz ( Site 2213)
🇺🇦Kyiv, Kyivska Oblast, Ukraine
Western General Hospital, Edinburgh ( Site 1924)
🇬🇧Edinburg, United Kingdom
Columbus Regional Research Institute ( Site 0098)
🇺🇸Columbus, Georgia, United States
Frontier Oncology ( Site 0080)
🇺🇸Billings, Montana, United States
University of Tennessee Medical Center Knoxville ( Site 0060)
🇺🇸Knoxville, Tennessee, United States
Disney Family Cancer Center ( Site 0005)
🇺🇸Burbank, California, United States
Hattiesburg Clinic ( Site 0045)
🇺🇸Hattiesburg, Mississippi, United States
Bozeman Health Deaconness Cancer Center ( Site 0046)
🇺🇸Bozeman, Montana, United States
Centro Oncológico de Rosario ( Site 0507)
🇦🇷Rosario, Santa Fe, Argentina
Instituto Medico Rio Cuarto ( Site 0501)
🇦🇷Rio Cuarto, Cordoba, Argentina
Thompson Cancer Survival Center ( Site 2812)
🇺🇸Knoxville, Tennessee, United States
Northwest Alabama Cancer Center, PC ( Site 0002)
🇺🇸Muscle Shoals, Alabama, United States
Cancer Care Northwest ( Site 0071)
🇺🇸Spokane Valley, Washington, United States
Klinikum Wels-Grieskirchen ( Site 1304)
🇦🇹Wels, Oberosterreich, Austria
Waverly Hematology Oncology ( Site 0081)
🇺🇸Cary, North Carolina, United States
Administradora Country S.A. ( Site 0603)
🇨🇴Bogota, Distrito Capital De Bogota, Colombia
CHU de Rouen ( Site 1403)
🇫🇷Rouen, Seine-Maritime, France
S.C. Centrul de Oncologie Sf. Nectarie SRL ( Site 2508)
🇷🇴Craiova, Dolj, Romania
Spitalul PDR Medlife ( Site 2509)
🇷🇴Brasov, Romania
Barbara Ann Karmanos Cancer Institute ( Site 0041)
🇺🇸Detroit, Michigan, United States
National Cancer Center ( Site 1006)
🇰🇷Goyang-si, Kyonggi-do, Korea, Republic of
Sanatorio Privado San Geronimo S.R.L ( Site 0510)
🇦🇷Santa Fe, Argentina
BC Cancer - Victoria ( Site 0109)
🇨🇦Victoria, British Columbia, Canada
Katholisches Marienkrankenhaus gGmbH ( Site 1522)
🇩🇪Hamburg, Germany
Sendai Kousei Hospital ( Site 0812)
🇯🇵Sendai, Miyagi, Japan
Klinikum Wuerzburg Mitte gGmbH ( Site 1509)
🇩🇪Wuerzburg, Bayern, Germany
FSAI Treatment and Rehabilitation Centre of the MoH and SD of RF ( Site 2006)
🇷🇺Moscow, Moskva, Russian Federation
Instituto do Cancer do Ceara ( Site 0201)
🇧🇷Fortaleza, Ceara, Brazil
Hospital Britanico de Buenos Aires ( Site 0500)
🇦🇷Buenos Aires, Caba, Argentina
Social Medical Center - Otto Wagner Hospital ( Site 1301)
🇦🇹Vienna, Wien, Austria
Krankenhaus Nord - Klinik Floridsdorf ( Site 1300)
🇦🇹Wien, Austria
YNOVA Pesquisa Clinica ( Site 0215)
🇧🇷Florianopolis, Santa Catarina, Brazil
Townsville General Hospital ( Site 1202)
🇦🇺Townsville, Queensland, Australia
National Cancer Center Hospital East ( Site 0801)
🇯🇵Kashiwa, Chiba, Japan
Kansai Medical University Hospital ( Site 0804)
🇯🇵Hirakata, Osaka, Japan
The Catholic University of Korea St. Vincent s Hospital ( Site 1003)
🇰🇷Suwon, Kyonggi-do, Korea, Republic of
Saint Gallen Instituto de Oncologia ( Site 0206)
🇧🇷Santa Cruz do Sul, Rio Grande Do Sul, Brazil
Ajou University Hospital ( Site 1004)
🇰🇷Suwon, Kyonggi-do, Korea, Republic of
Queen Elizabeth II Health Sciences Centre ( Site 0107)
🇨🇦Halifax, Nova Scotia, Canada
Helios Klinikum Erfurt GmbH ( Site 1502)
🇩🇪Erfurt, Thuringen, Germany
Centro de Novos Tratamentos Itajai - Clinica de Neoplasias Litoral ( Site 0202)
🇧🇷Itajai, Santa Catarina, Brazil
Hospital Paulistano - Amil Clinical Research ( Site 0207)
🇧🇷Sao Paulo, Brazil
Hopital d'Instruction des Armees Begin ( Site 1413)
🇫🇷Saint-Mande, Val-de-Marne, France
Pneumologische Lehrklinik Universitaet Goettingen ( Site 1501)
🇩🇪Immenhausen, Hessen, Germany
Health Sciences North Research Institute ( Site 0115)
🇨🇦Sudbury, Ontario, Canada
Chungbuk National University Hospital ( Site 1002)
🇰🇷Cheongju si, Chungbuk, Korea, Republic of
Kliniken Essen Mitte ( Site 1517)
🇩🇪Essen, Nordrhein-Westfalen, Germany
Kanazawa University Hospital ( Site 0811)
🇯🇵Kanazawa, Ishikawa, Japan
Kanagawa Cancer Center ( Site 0807)
🇯🇵Yokohama, Kanagawa, Japan
Korea University Guro Hospital ( Site 1008)
🇰🇷Seoul, Korea, Republic of
Klinikum Bogenhausen Staedt. Klinikum Muenchen GmbH ( Site 1523)
🇩🇪Muenchen, Bayern, Germany
Ordensklinikum Linz GmbH Elisabethinen ( Site 1307)
🇦🇹Linz, Oberosterreich, Austria
Hospital Sao Rafael ( Site 0212)
🇧🇷Salvador, Bahia, Brazil
Hospital de Base de Sao Jose de Rio Preto ( Site 0204)
🇧🇷Sao Jose Rio Preto, Sao Paulo, Brazil
Instituto Nacional do Cancer Jose Alencar Gomes da Silva INCA ( Site 0203)
🇧🇷Rio de Janeiro, Brazil
Fundacion Colombiana de Cancerologia Clinica Vida ( Site 0604)
🇨🇴Medellin, Antioquia, Colombia
Clinica de la Costa Ltda. ( Site 0608)
🇨🇴Barranquilla, Atlantico, Colombia
Centre Hospitalier De Chauny ( Site 1411)
🇫🇷Chauny, Aisne, France
CHU Caen ( Site 1406)
🇫🇷Caen, Calvados, France
CIUSSS Ouest de l Ile - St-Mary s Hospital ( Site 0110)
🇨🇦Montreal, Quebec, Canada
Klinikum der LMU ( Site 1500)
🇩🇪Munich, Bayern, Germany
CHU Angers ( Site 1405)
🇫🇷Angers, Maine-et-Loire, France
Institut De Cancerologie De Lorraine ( Site 1409)
🇫🇷Vandoeuvre les Nancy, Meurthe-et-Moselle, France
Hopital Robert Schuman ( Site 1402)
🇫🇷Vantoux, Moselle, France
Niigata Cancer Center Hospital ( Site 0808)
🇯🇵Niigata, Japan
Szpital Rejonowy im. dr Jozefa Rostka ( Site 2402)
🇵🇱Raciborz, Slaskie, Poland
Namik Kemal Universitesi Tip Fakultesi ( Site 2100)
🇹🇷Tekirdag, Tekirdas, Turkey
Gazi Universitesi Tip Fakultesi ( Site 2104)
🇹🇷Ankara, Turkey
Barts Health NHS Trust - St Bartholomew s Hospital ( Site 1923)
🇬🇧London, London, City Of, United Kingdom
Moscow Regional Oncological Dispensary ( Site 2028)
🇷🇺Balashikha, Moskovskaya Oblast, Russian Federation
Aichi Cancer Center Hospital ( Site 0803)
🇯🇵Nagoya, Aichi, Japan
Okayama University Hospital ( Site 0810)
🇯🇵Okayama, Japan
Asan Medical Center ( Site 1007)
🇰🇷Songpa-gu, Seoul, Korea, Republic of
Wielospecjalistyczny Szpital SPZOZ w Zgorzelcu ( Site 2404)
🇵🇱Zgorzelec, Dolnoslaskie, Poland
Universitaetsmedizin Goettingen ( Site 1507)
🇩🇪Goettingen, Niedersachsen, Germany
Universitaetsklinikum Frankfurt ( Site 1513)
🇩🇪Frankfurt, Hessen, Germany
Shizuoka Cancer Center Hospital and Research Institute ( Site 0802)
🇯🇵Sunto-gun, Shizuoka, Japan
National Hospital Organization Nagoya Medical Center ( Site 0806)
🇯🇵Nagoya, Aichi, Japan
Cardiomed SRL Cluj-Napoca ( Site 2504)
🇷🇴Cluj Napoca, Cluj, Romania
S.C.Focus Lab Plus S.R.L ( Site 2502)
🇷🇴Bucuresti, Romania
China Medical University Hospital ( Site 0904)
🇨🇳Taichung, Taiwan
Samsun Ondokuz Mayis Universitesi Tip Fakultesi Hastanesi ( Site 2106)
🇹🇷Samsun, Turkey
Hospital del Mar ( Site 1702)
🇪🇸Barcelona, Spain
SBHI Leningrad Regional Clinical Hospital ( Site 2002)
🇷🇺Saint Petersburg, Leningradskaya Oblast, Russian Federation
Policlinica Oncomed SRL ( Site 2505)
🇷🇴Timisoara, Timis, Romania
Samodzielny Publiczny Zespol Gruzlicy i Chorob Pluc ( Site 2417)
🇵🇱Olsztyn, Warminsko-mazurskie, Poland
MED-POLONIA Sp. z o.o. ( Site 2419)
🇵🇱Poznan, Wielkopolskie, Poland
Hospital Universitario Nuestra Senora de Valme ( Site 1703)
🇪🇸Sevilla, Spain
Hospital Clinico Universitario de Valencia ( Site 1706)
🇪🇸Valencia, Valenciana, Comunitat, Spain
Chang Gung Medical Foundation. Kaohsiung Branch ( Site 0907)
🇨🇳Kaohsiung, Taiwan
National Cheng Kung University Hospital ( Site 0905)
🇨🇳Tainan, Taiwan
Chang Gung Medical Foundation.Linkou Branch ( Site 0903)
🇨🇳Taoyuan, Taiwan
PP PPC Acinus Medical and Diagnostic Centre ( Site 2209)
🇺🇦Kropyvnitskiy, Kirovohradska Oblast, Ukraine
Medical Center Asklepion LLC ( Site 2234)
🇺🇦Khodosivka, Kyivska Oblast, Ukraine
Hospital Universitario Quiron Madrid ( Site 1701)
🇪🇸Pozuelo de Alarcon, Madrid, Spain
Hospital Clinico Lozano Blesa ( Site 1700)
🇪🇸Zaragoza, Spain
Medical Center Verum ( Site 2230)
🇺🇦Kyiv, Ukraine
Mackay Memorial Hospital ( Site 0902)
🇨🇳Taipei, Taiwan
Regional Centre of Oncology-Thoracic organs ( Site 2205)
🇺🇦Kharkiv, Kharkivska Oblast, Ukraine
Ankara Sehir Hastanesi ( Site 2105)
🇹🇷Ankara, Turkey
Cherkasy Regional Oncology Dispensary ( Site 2211)
🇺🇦Cherkasy, Cherkaska Oblast, Ukraine
Kyiv City Clinical Oncology Centre ( Site 2210)
🇺🇦Kyiv, Ukraine
Central City Clinical Hospital ( Site 2207)
🇺🇦Uzhgorod, Zakarpatska Oblast, Ukraine
Birmingham Heartlands Hospital ( Site 1910)
🇬🇧Birmingham, United Kingdom
West Suffolk Hospitals NHS Trust ( Site 1919)
🇬🇧Bury Saint Edmunds, Suffolk, United Kingdom
Singleton Hospital ( Site 1909)
🇬🇧Swansea, United Kingdom
National Hospital Organization Kyushu Medical Center ( Site 0805)
🇯🇵Fukuoka, Japan
Osaka International Cancer Institute ( Site 0809)
🇯🇵Osaka, Japan
Göztepe Prof. Dr. Süleyman Yalçın Şehir Hastanesi-oncology ( Site 2103)
🇹🇷Istanbul, Turkey
Erciyes Universitesi Tip Fakultesi ( Site 2108)
🇹🇷Kayseri, Turkey
Oncologica do Brasil ( Site 0210)
🇧🇷Belem, Para, Brazil
Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 0200)
🇧🇷Sao Paulo, Brazil
Real e Benemerita Associacao Portuguesa de Beneficencia ( Site 0214)
🇧🇷Sao Paulo, Brazil
Grand River Hospital ( Site 0117)
🇨🇦Kitchener, Ontario, Canada
CISSS de la Monteregie-Centre ( Site 0114)
🇨🇦Greenfield Park, Quebec, Canada
Centre de Sante et des Services Sociaux de Rimouski-Neigette ( Site 0104)
🇨🇦Rimouski, Quebec, Canada
Universitaetsklinikum Regensburg ( Site 1512)
🇩🇪Regensburg, Bayern, Germany
Alabama Oncology Bruno Cancer Center ( Site 0001)
🇺🇸Birmingham, Alabama, United States
First Moscow State Medical University n.a. I.M.Sechenov ( Site 2024)
🇷🇺Moscow, Moskva, Russian Federation
Nizhniy Novgorod Region Oncology Dispensary ( Site 2026)
🇷🇺Nizhniy Novgorod, Nizhegorodskaya Oblast, Russian Federation
Budgetary Healthcare Institution of Omsk Region Clinical Oncology Dispensary-Chemotherapy #1 ( Site
🇷🇺Omsk, Omskaya Oblast, Russian Federation
Hospital Italiano Regional del Sur ( Site 0509)
🇦🇷Bahia Blanca, Buenos Aires, Argentina
Clínica Universitaria Reina Fabiola ( Site 0505)
🇦🇷Cordoba, Argentina
Moffitt Cancer Center ( Site 0024)
🇺🇸Tampa, Florida, United States
National Taiwan University Hospital ( Site 0900)
🇨🇳Taipei, Taiwan
MI Precarpathian Clinical Oncology Center ( Site 2204)
🇺🇦Ivano-Frankivsk, Ivano-Frankivska Oblast, Ukraine
SPb Central Clinical Railway Hospital ( Site 2003)
🇷🇺Saint Petersburg, Sankt-Peterburg, Russian Federation
Methodists Hospitals/Premier Oncology Hematology Associates ( Site 0036)
🇺🇸Merrillville, Indiana, United States
Oncology of Northshore ( Site 0033)
🇺🇸Rolling Meadows, Illinois, United States
Mid-Florida Cancer Centers ( Site 0022)
🇺🇸Orange City, Florida, United States
Mount Sinai Hospital Medical Center ( Site 0032)
🇺🇸Chicago, Illinois, United States
Centro Medico San Roque ( Site 0506)
🇦🇷San Miguel de Tucuman, Tucuman, Argentina
Hospital Italiano de Buenos Aires ( Site 0511)
🇦🇷Buenos Aires, Argentina
Innsbruck LKH ( Site 1302)
🇦🇹Innsbruck, Tirol, Austria
Southern Medical Day Care Centre ( Site 1200)
🇦🇺Wollongong, New South Wales, Australia
Monash Cancer Centre ( Site 1205)
🇦🇺Clayton, Victoria, Australia
Centro de Hematologia e Oncologia ( Site 0205)
🇧🇷Joinville, Santa Catarina, Brazil
Lions Gate Hospital ( Site 0106)
🇨🇦North Vancouver, British Columbia, Canada
Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0105)
🇨🇦Montreal, Quebec, Canada
CIUSSS de l Estrie - CHUS - Centre Hosp. Univ. Sherbrooke ( Site 0103)
🇨🇦Sherbrooke, Quebec, Canada
Centre Jean Perrin ( Site 1407)
🇫🇷Clermont Ferrand, Puy-de-Dome, France
Studienzentrum Aschaffenburg ( Site 1525)
🇩🇪Aschaffenburg, Bayern, Germany
Centre Hospitalier de Pau ( Site 1412)
🇫🇷Pau, Pyrenees-Atlantiques, France
InVo-Institut fuer Versorgungsforschung in der Onkologie ( Site 1514)
🇩🇪Koblenz, Rheinland-Pfalz, Germany
Universitaetsklinikum Bonn ( Site 1524)
🇩🇪Bonn, Nordrhein-Westfalen, Germany
The Cancer Institute Hospital of JFCR ( Site 0800)
🇯🇵Tokyo, Japan
National Hospital Organization Kinki-chuo Chest Medical Center ( Site 0813)
🇯🇵Sakai, Osaka, Japan
Gyeongsang National University Hospital ( Site 1005)
🇰🇷Jinju, Kyongsangnam-do, Korea, Republic of
Seoul National University Hospital ( Site 1000)
🇰🇷Seoul, Korea, Republic of
MidCentral DHB Palmerston North Hospital ( Site 1102)
🇳🇿Palmerston North, Manawatu-Wanganui, New Zealand
Capital & Coast District Health Board - Wellington Hospital ( Site 1101)
🇳🇿Wellington, New Zealand
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie (
🇵🇱Warszawa, Mazowieckie, Poland
Moscow Research Oncology Institute named after P.A. Hertsen ( Site 2009)
🇷🇺Moscow, Moskva, Russian Federation
SBHI Samara Regional Clinical Oncology Dispensary ( Site 2016)
🇷🇺Samara, Samarskaya Oblast, Russian Federation
Russian Oncological Research Center n.a. N.N.Blokhin of MoH ( Site 2000)
🇷🇺Moscow, Moskva, Russian Federation
National Medical Research Center of Oncology N.A. N.N. Petrov ( Site 2004)
🇷🇺Saint Petersburg, Sankt-Peterburg, Russian Federation
SPb SBHI City Clinical Oncological Dispensary ( Site 2001)
🇷🇺Saint Petersburg, Sankt-Peterburg, Russian Federation
Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 2021)
🇷🇺Kazan, Tatarstan, Respublika, Russian Federation
Baskent Unv. Adana Uyg. ve Arast. Hastanesi ( Site 2101)
🇹🇷Adana, Turkey
Bezmialem Vakif Univ. Tıp Fakultesi Hastanesi Tibbi Onkoloji Bolumu ( Site 2107)
🇹🇷Istanbul, Turkey
Ege Universitesi Tip Fakultesi ( Site 2109)
🇹🇷Izmir, Turkey
Chelsea and Westminster Hospital ( Site 1901)
🇬🇧London, London, City Of, United Kingdom
Colchester General Hospital ( Site 1911)
🇬🇧Colchester, Worcestershire, United Kingdom
Boca Raton Regional Hospital ( Site 0018)
🇺🇸Boca Raton, Florida, United States
Krakowski Szpital Specjalistyczny im Jana Pawla II ( Site 2420)
🇵🇱Krakow, Malopolskie, Poland
Irmandade da Santa Casa de Misericordia de Porto Alegre ( Site 0209)
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
MI Odessa Regional Oncological Centre ( Site 2208)
🇺🇦Odesa, Odeska Oblast, Ukraine