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Trial record 1 of 1 for:    NCT03976323
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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)

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ClinicalTrials.gov Identifier: NCT03976323
Recruitment Status : Recruiting
First Posted : June 6, 2019
Last Update Posted : November 9, 2020
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE June 3, 2019
First Posted Date  ICMJE June 6, 2019
Last Update Posted Date November 9, 2020
Actual Study Start Date  ICMJE June 28, 2019
Estimated Primary Completion Date August 13, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 3, 2019)
  • Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [ Time Frame: Up to approximately 3 years ]
    Progression-free survival is the time from the date of randomization until either documented disease progression or death due to any cause, whichever occurs first.
  • Overall Survival (OS) [ Time Frame: Up to approximately 5 years ]
    Overall survival is the time from the date of randomization to death due to any cause.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 3, 2019)
  • Number of Participants Experiencing an Adverse Event (AE) [ Time Frame: Up to approximately 5 years ]
    An adverse event (AE) is 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 is considered related to the medical treatment or procedure, that occurs during the course of the study.
  • Number of Participants Discontinuing Study Treatment Due to Adverse Event (AE) [ Time Frame: Up to approximately 5 years ]
    An AE is 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 is considered related to the medical treatment or procedure, that occurs during the course of the study.
  • 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 [ Time Frame: Baseline (at randomization) and Week 18 post-randomization ]
    The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the question "How would you rate your overall health during the past week?" are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. The change from baseline in EORTC QLQ-C30 Items 29 and 30 scores will be presented.
  • Change from Baseline in EORTC Quality of Life Questionnaire Lung Cancer Module 13 (QLQ-LC13) Cough (Item 1) Scale Score [ Time Frame: Baseline (at randomization) and Week 18 post-randomization ]
    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 will be presented.
  • Change from Baseline in EORTC QLQ-LC13 Chest Pain (Item 10) Scale Score [ Time Frame: Baseline (at randomization) and Week 18 post-randomization ]
    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 was your chest pain?" 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 will be presented.
  • Change from Baseline in EORTC QLQ-C30 Dyspnea (Item 8) Scale Score [ Time Frame: Baseline (at randomization) and Week 18 post-randomization ]
    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. The change from baseline in EORTC QLQ-LC13 dyspnea (Item 8) score will be presented.
  • Change from Baseline in EORTC QLQ-C30 Physical Functioning (Items 1 to 5) Scale Score [ Time Frame: Baseline (at randomization) and Week 18 post-randomization ]
    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. The change from baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) score will be presented.
  • Time to True Deterioration (TTD) in EORTC QLQ-C30 Global Health Status / Quality of Life (Items 29 & 30) Scale Score [ Time Frame: Up to approximately 5 years ]
    The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the question "How would you rate your overall health during the past week?" are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. 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 EORTC QLQ-C30 Items 29 and 30 scale scores.
  • Time to True Deterioration (TTD) in EORTC Quality of Life Questionnaire Lung Cancer Module 13 (QLQ-LC13) Cough (Item 1) Scale Score [ Time Frame: Up to approximately 5 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 EORTC QLQ-LC13 cough (Item 1) scale score.
  • Time to True Deterioration (TTD) in EORTC (QLQ-LC13 Chest Pain (Item 10) Scale Score [ Time Frame: Up to approximately 5 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 was your chest pain?" 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 EORTC QLQ-LC13 chest pain (Item 10) scale score.
  • Time to True Deterioration (TTD) in EORTC QLQ-C30 Dyspnea (Item 8) Scale Score [ Time Frame: Up to approximately 5 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 EORTC QLQ-C30 dyspnea (Item 8) scale score.
  • Time to True Deterioration (TTD) in EORTC QLQ-C30 Physical Functioning (Items 1 to 5) Scale Score [ Time Frame: Up to approximately 5 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 EORTC QLQ-C30 physical functioning (Items 1 to 5) scale scores.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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)
Official Title  ICMJE A Phase 3 Study of Pembrolizumab in Combination With Pemetrexed/Platinum (Carboplatin or Cisplatin) Followed by Pembrolizumab and Maintenance Olaparib vs Maintenance Pemetrexed in the First-Line Treatment of Participants With Metastatic Nonsquamous Non-Small-Cell Lung Cancer
Brief Summary The current study will compare pembrolizumab (MK-3475) plus maintenance olaparib, v.s. pembrolizumab plus maintenance pemetrexed for the treatment of nonsquamous 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 (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 (4 Cycles) and a Maintenance Phase (Up to 31 cycles of pembrolizumab). In the Induction Phase, participants receive pembrolizumab plus pemetrexed plus platinum (carboplatin or cisplatin). 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 plus maintenance olaparib OR maintenance pemetrexed until progressive disease (PD), intolerable toxicities, or physician decision.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Carcinoma, Non-squamous Non-small-cell Lung
Intervention  ICMJE
  • Biological: Pembrolizumab
    IV infusion
    Other Names:
    • MK-3475
    • KEYTRUDA®
  • Drug: Pemetrexed
    IV infusion
    Other Name: ALIMTA®
  • Drug: Carboplatin
    IV infusion
    Other Name: PARAPLATIN®
  • Drug: Cisplatin
    IV infusion
    Other Names:
    • PLATINOL®
    • PLATINOL®-AQ
  • Drug: Olaparib
    Tablets
    Other Name: LYNPARZA®
Study Arms  ICMJE
  • Experimental: Pembrolizumab + Pemetrexed + Platinum Therapy + Olaparib

    For the Induction Phase, participants receive 4 cycles:

    Pembrolizumab 200 mg intravenous (IV) on Day 1 of each 21-day cycle (cycles 1 through 4) PLUS Pemetrexed 500 mg/m^2 IV on Day 1 of each 21-day 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 21-day cycle (Cycles 1 through 4) OR cisplatin 75 mg/m^2 IV on Day 1 of 21-day cycle (Cycles 1 through 4).

    If the participant has a complete or partial response or stable disease to induction therapy, the participant is randomized to maintenance therapy.

    For the Maintenance Phase, participants receive Pembrolizumab IV on Day 1 of each 21-day cycle for up to 31 cycles PLUS maintenance oral olaparib 300 mg twice daily. In the Maintenance Phase, the participant continues to receive maintenance olaparib until progressive disease, physician decision or intolerable toxicity.

    Interventions:
    • Biological: Pembrolizumab
    • Drug: Pemetrexed
    • Drug: Carboplatin
    • Drug: Cisplatin
    • Drug: Olaparib
  • Active Comparator: Pembrolizumab + Pemetrexed + Platinum Therapy + Pemetrexed

    For the Induction Phase, participants receive 4 cycles:

    Pembrolizumab 200 mg intravenous (IV) on Day 1 of each 21-day cycle (cycles 1 through 4) PLUS Pemetrexed 500 mg/m^2 IV on Day 1 of each 21-day 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 21-day cycle (Cycles 1 through 4) OR cisplatin 75 mg/m2 IV on Day 1 of 21-day cycle (Cycles 1 through 4). If the participant has a complete or partial response or stable disease to induction therapy, the participant is randomized to maintenance therapy. For the Maintenance Phase, participants receive Pembrolizumab IV on Day 1 of each 21 day-cycle for up to 31 cycles PLUS maintenance pemetrexed IV 500 mg/m^2 on Day 1 of each 21-day cycle. In the maintenance phase, the participant continues to receive maintenance pemetrexed until progressive disease, physician decision or intolerable toxicity.

    Interventions:
    • Biological: Pembrolizumab
    • Drug: Pemetrexed
    • Drug: Carboplatin
    • Drug: Cisplatin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 3, 2019)
792
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 30, 2024
Estimated Primary Completion Date August 13, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 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 not completed palliative radiotherapy within 7 days of the first dose. Participants must have recovered from all radiation-related toxicities and not require corticosteroids.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com
Listed Location Countries  ICMJE Argentina,   Australia,   Austria,   Brazil,   Canada,   Colombia,   France,   Germany,   Japan,   Korea, Republic of,   New Zealand,   Poland,   Romania,   Russian Federation,   Spain,   Taiwan,   Turkey,   Ukraine,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03976323
Other Study ID Numbers  ICMJE 7339-006
MK-7339-006 ( Other Identifier: Merck Protocol Number )
2018-004720-11 ( EudraCT Number )
KEYLYNK-006 ( Other Identifier: Merck )
194895 ( Registry Identifier: JAPIC-CTI )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme Corp.
PRS Account Merck Sharp & Dohme Corp.
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP