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Placebo-controlled, Study of Concurrent Chemoradiation Therapy With Pembrolizumab Followed by Pembrolizumab and Olaparib in Newly Diagnosed Treatment-Naïve Limited-Stage Small Cell Lung Cancer (LS-SCLC) (MK 7339-013/KEYLYNK-013)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04624204
Recruitment Status : Recruiting
First Posted : November 10, 2020
Last Update Posted : June 11, 2021
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:

The purpose of this study is to compare overall survival (OS) and progression free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by blinded independent central review (BICR).

Hypothesis (H1): Concurrent chemoradiation therapy with pembrolizumab followed by pembrolizumab plus olaparib is superior to concurrent chemoradiation therapy alone with respect to PFS per RECIST 1.1 by BICR.

Hypothesis (H2): Concurrent chemoradiation therapy with pembrolizumab followed by pembrolizumab is superior to concurrent chemoradiation therapy alone with respect to PFS per RECIST 1.1 by BICR.

Hypothesis (H3): Concurrent chemoradiation therapy with pembrolizumab followed by pembrolizumab plus olaparib is superior to concurrent chemoradiation therapy alone with respect to OS.

Hypothesis (H4): Concurrent chemoradiation therapy with pembrolizumab followed by pembrolizumab is superior to concurrent chemoradiation therapy alone with respect to OS.


Condition or disease Intervention/treatment Phase
Small Cell Lung Cancer Biological: Pembrolizumab 200 mg Biological: Pembrolizumab 400 mg Drug: Pembrolizumab placebo (saline) Drug: Olaparib 300 mg BID Drug: Olaparib matching placebo Drug: Etoposide 100 mg/m^2 Drug: Platinum, investigator's choice Radiation: Standard Thoracic Radiotherapy Radiation: Prophylactic Cranial Irradiation (PCI) Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 672 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled Phase 3 Study of Pembrolizumab (MK-3475) in Combination With Concurrent Chemoradiation Therapy Followed by Pembrolizumab With or Without Olaparib (MK-7339), Compared to Concurrent Chemoradiation Therapy Alone in Participants With Newly Diagnosed Treatment-Naïve Limited-Stage Small Cell Lung Cancer (LS-SCLC)
Actual Study Start Date : December 8, 2020
Estimated Primary Completion Date : October 28, 2027
Estimated Study Completion Date : October 28, 2027

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Group A - Pembrolizumab 200 mg
Participants will receive 4 cycles of standard-of-care chemotherapy (etoposide/platinum) plus pembrolizumab 200 mg every 3 weeks (Q3W) concurrently with standard thoracic radiotherapy, followed by 9 cycles of pembrolizumab 400 mg every 6 weeks (Q6W) plus olaparib matching placebo twice daily (BID) for 12 months or until specific discontinuation criteria are met.
Biological: Pembrolizumab 200 mg
Pembrolizumab 200 mg Q3W
Other Names:
  • MK-3475
  • KEYTRUDA®

Biological: Pembrolizumab 400 mg
Pembrolizumab 400 mg Q6W
Other Names:
  • MK-3475
  • KEYTRUDA®

Drug: Olaparib matching placebo
Olaparib matching placebo BID

Drug: Etoposide 100 mg/m^2
Etoposide 100 mg/m^2 intravenous (IV) Q3W, Day 1-3

Drug: Platinum, investigator's choice
Carboplatin titrated to an area under the plasma drug concentration time curve (AUC) of 5 mg/mL/min IV Q3W OR Cisplatin 75 mg/m^2 IV Q3W on Day 1 of each cycle

Radiation: Standard Thoracic Radiotherapy
Standard Thoracic Radiotherapy

Radiation: Prophylactic Cranial Irradiation (PCI)
PCI will be strongly recommended for participants who achieve CR or PR after completion of chemoradiation treatment.

Experimental: Group B - Pembrolizumab 200 mg plus Olaparib 300 mg BID
Participants will receive 4 cycles of standard-of-care chemotherapy (etoposide/platinum) plus pembrolizumab 200 mg Q3W concurrently with standard thoracic radiotherapy, followed by 9 cycles of pembrolizumab 400 mg Q6W plus olaparib 300 mg BID for 12 months or until specific discontinuation criteria are met.
Biological: Pembrolizumab 200 mg
Pembrolizumab 200 mg Q3W
Other Names:
  • MK-3475
  • KEYTRUDA®

Biological: Pembrolizumab 400 mg
Pembrolizumab 400 mg Q6W
Other Names:
  • MK-3475
  • KEYTRUDA®

Drug: Olaparib 300 mg BID
Olaparib 300 mg twice daily (BID)
Other Names:
  • MK-7339
  • LYNPARZA®

Drug: Etoposide 100 mg/m^2
Etoposide 100 mg/m^2 intravenous (IV) Q3W, Day 1-3

Drug: Platinum, investigator's choice
Carboplatin titrated to an area under the plasma drug concentration time curve (AUC) of 5 mg/mL/min IV Q3W OR Cisplatin 75 mg/m^2 IV Q3W on Day 1 of each cycle

Radiation: Standard Thoracic Radiotherapy
Standard Thoracic Radiotherapy

Radiation: Prophylactic Cranial Irradiation (PCI)
PCI will be strongly recommended for participants who achieve CR or PR after completion of chemoradiation treatment.

Placebo Comparator: Group C (Pembrolizumab and Olaparib Matching Placebos)
Participants will receive 4 cycles of standard-of-care chemotherapy (etoposide/platinum) plus pembrolizumab placebo (saline) Q3W concurrently with standard thoracic radiotherapy, followed by 9 cycles of pembrolizumab placebo (saline) Q6W plus olaparib matching placebo for 12 months or until specific discontinuation criteria are met.
Drug: Pembrolizumab placebo (saline)
Pembrolizumab placebo (saline) Q3W

Drug: Pembrolizumab placebo (saline)
Pembrolizumab placebo (saline) Q6W

Drug: Olaparib matching placebo
Olaparib matching placebo BID

Drug: Etoposide 100 mg/m^2
Etoposide 100 mg/m^2 intravenous (IV) Q3W, Day 1-3

Drug: Platinum, investigator's choice
Carboplatin titrated to an area under the plasma drug concentration time curve (AUC) of 5 mg/mL/min IV Q3W OR Cisplatin 75 mg/m^2 IV Q3W on Day 1 of each cycle

Radiation: Standard Thoracic Radiotherapy
Standard Thoracic Radiotherapy

Radiation: Prophylactic Cranial Irradiation (PCI)
PCI will be strongly recommended for participants who achieve CR or PR after completion of chemoradiation treatment.




Primary Outcome Measures :
  1. Progression-free Survival Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1); the time from randomization to progression or death due to any cause, whichever occurs first [ Time Frame: Up to approximately 59 months ]
    Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) is the time from randomization to progression or death due to any cause, whichever occurs first.

  2. Overall Survival: the time from randomization to death due to any cause [ Time Frame: Up to approximately 82 months ]
    Overall Survival (OS) is the time from randomization to death due to any cause.


Secondary Outcome Measures :
  1. Number of Participants Experiencing an Adverse Events (AEs) [ Time Frame: Up to approximately 82 months ]
    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.

  2. Number of Participants Discontinuing Study Treatment Due to Adverse Events (AEs) [ Time Frame: Up to approximately 82 months ]
    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.

  3. Objective Response (OR): Complete Response (CR) or Partial Response (PR) [ Time Frame: Up to approximately 82 months ]
    Percentage of participants in the analysis population who have a best overall response of either confirmed CR or a PR per RECIST 1.1.

  4. Duration of Response (DOR): the time from the earliest date of first documented evidence of confirmed CR or PR until the earliest date of disease progression or death from any cause, whichever comes first [ Time Frame: Up to approximately 82 months ]
    DOR is the time from the earliest date of first documented evidence of confirmed CR or PR until the earliest date of disease progression or death from any cause, whichever comes first.

  5. Change from Baseline at Cycle 1 in European Organization for Research and Treatment (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status / Quality of Life (Items 29 & 30) Scale Score [ Time Frame: Baseline and 82 months 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.

  6. Change from Baseline at Cycle 1 in EORTC Quality of Life Questionnaire Lung Cancer Module 13 (QLQ-LC13) Cough (Item 1) Scale Score [ Time Frame: Baseline and 82 months post randomization ]
    The EORTC QLQ-LC13 is a lung cancer specific supplemental questionnaire used in combination with the EORTC QLQC30 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.

  7. Change from Baseline at Cycle 1 in EORTC QLQ-LC13 Chest Pain (Item 10) Scale Score [ Time Frame: Baseline and 82 months post randomization ]
    The EORTC QLQ-LC13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQC30 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.

  8. Change from Baseline at Cycle 1 in EORTC QLQ-C30 Dyspnea (Item 8) Scale Score [ Time Frame: Baseline and 82 months 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.

  9. Change from Baseline at Cycle 1 in EORTC QLQ-C30 Physical Functioning (Items 1 to 5) Scale Score [ Time Frame: Baseline and 82 months 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.

  10. 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 82 months 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. 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.

  11. Time to True Deterioration (TTD) in Cough (LC13/Item 1) Scale Score [ Time Frame: Up to approximately 82 months post randomization ]
    The EORTC QLQ-LC13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQC30 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 QLQLC13 cough (Item 1) scale score.

  12. Time to True Deterioration (TTD) in Chest Pain (LC13/Item 10) Scale Score [ Time Frame: Up to approximately 82 months post randomization ]
    The EORTC QLQ-LC13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQC30 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.

  13. Time to True Deterioration (TTD) in EORTC QLQ-C30 Dyspnea (Item 8) Scale Score [ Time Frame: Up to approximately 82 months 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. 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.

  14. Time to True Deterioration (TTD) in EORTC QLQ-C30 Physical Functioning (Items 1 to 5) Scale Score [ Time Frame: Up to approximately 82 months 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. 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.

  15. Objective Response (OR, according to RECIST 1.1 by BICR) assessed by programmed cell death ligand 1 (PD-L1) expression levels [ Time Frame: Up to approximately 82 months ]
    Percentage of participants in the analysis population who have a best overall response of either confirmed CR or a PR per RECIST 1.1, analyzed by programmed cell death ligand 1 (PD-L1) expression levels.

  16. Duration of Response (DOR, according to RECIST 1.1 by BICR) assessed by programmed cell death ligand 1 (PD-L1) expression levels [ Time Frame: Up to approximately 82 months ]
    DOR is the time from the earliest date of first documented evidence of confirmed CR or PR until the earliest date of disease progression or death from any cause, whichever comes first, analyzed by programmed cell death ligand 1 (PD-L1) expression levels.

  17. Progression-free Survival (PFS, according to RECIST 1.1 by BICR) assessed by programmed cell death ligand 1 (PD-L1) expression levels [ Time Frame: Up to approximately 59 months ]
    Progression-free Survival Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1); the time from randomization to progression or death due to any cause, whichever occurs first, analyzed by programmed cell death ligand 1 (PD-L1) expression levels.

  18. Overall Survival (OS) assessed by programmed cell death ligand 1 (PD-L1) expression levels [ Time Frame: Up to approximately 82 months ]
    Overall Survival: the time from randomization to death due to any cause, analyzed by programmed cell death ligand 1 (PD-L1) expression levels.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Has pathologically (histologically or cytologically) confirmed Small Cell Lung Cancer (SCLC).
  2. Has Limited-Stage SCLC (Stage I-III, by AJCC 8th Edition Cancer Staging), and can be safely treated with definitive radiation doses.
  3. Has no evidence of metastatic disease by whole body positron emission tomography /computed tomography (PET/CT scan), CT or magnetic resonance imaging (MRI) scans
  4. Has at least 1 lesion that meets the criteria for being measurable, as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
  5. Has not received prior treatment (chemotherapy or radiotherapy or surgery resection) of LS-SCLC.
  6. Is not expected to require tumor resection during the course of the study.
  7. Must submit a pre-treatment tumor tissue sample (formalin-fixed, paraffin embedded blocks are preferred to slides) including cytologic sample, if tissue sample unavailable.
  8. Has Eastern Cooperative Oncology Group (ECOG) Performance score 0 or 1 assessed within 7 days prior to the first administration of study intervention.
  9. Has a life expectancy of at least 6 months.
  10. Has adequate organ function.
  11. 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.
  12. Male and female participants who are at least 18 years of age at the time of signing the information consent.
  13. Male participants must refrain from donating sperm during the treatment period and for 180 days afterwards.

Exclusion Criteria:

  1. Has history, current diagnosis, or features suggestive of myelodysplastic syndrome/ acute myeloid leukemia (MDS/AML).
  2. Has received prior therapy with an anti-programmed cell death 1 (anti-PD-1), anti-programmed cell death ligand 1 (anti-PDL1), or anti- programmed cell death ligand 2 (anti-PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor
  3. Has received prior therapy with olaparib or with any other polyadenosine 5'diphosphoribose (polyADP ribose) polymerization (PARP) inhibitor.
  4. Had major surgery <4 weeks prior to the first dose of study intervention (except for placement of vascular access).
  5. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
  6. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention.
  7. Has a known additional malignancy that is progressing or has required active treatment within the past 5 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
  8. Has severe hypersensitivity (≥ Grade 3) to study intervention and/or any of its excipients.
  9. Has an active autoimmune disease that has required systemic treatment in past 2 years
  10. Has a history of (non-infectious) pneumonitis/interstitial lung disease that requires steroids
  11. Has an active infection requiring systemic therapy.
  12. Has a known history of human immunodeficiency virus (HIV) infection or Hepatitis B or known active Hepatitis C virus infection.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04624204


Contacts
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Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

Locations
Show Show 93 study locations
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Medical Director, MD Merck Sharp & Dohme Corp.
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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT04624204    
Other Study ID Numbers: 7339-013
MK-7339-013 ( Other Identifier: Merck Protocol Number )
2019-003616-31 ( EudraCT Number )
jRCT2031200296 ( Registry Identifier: jRCT )
First Posted: November 10, 2020    Key Record Dates
Last Update Posted: June 11, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Merck Sharp & Dohme Corp.:
Programmed Cell Death-1 (PD1, PD-1)
Programmed Death-Ligand 1 (PDL1, PD-L1)
Pembrolizumab
Olaparib
Additional relevant MeSH terms:
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Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Pembrolizumab
Etoposide
Olaparib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Poly(ADP-ribose) Polymerase Inhibitors