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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)

NCT04624204

Description:

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.

Related Conditions:
  • Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

URL:

https://clinicaltrials.gov/show/NCT04624204

Trial Eligibility

Document

Title

  • Brief Title: 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)
  • 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)

Clinical Trial IDs

  • ORG STUDY ID: 7339-013
  • SECONDARY ID: MK-7339-013
  • SECONDARY ID: 2019-003616-31
  • SECONDARY ID: jRCT2031200296
  • NCT ID: NCT04624204

Conditions

  • Small Cell Lung Cancer

Interventions

DrugSynonymsArms
Pembrolizumab 200 mgMK-3475, KEYTRUDA®Group A - Pembrolizumab 200 mg
Pembrolizumab 400 mgMK-3475, KEYTRUDA®Group A - Pembrolizumab 200 mg
Pembrolizumab placebo (saline)Group C (Pembrolizumab and Olaparib Matching Placebos)
Pembrolizumab placebo (saline)Group C (Pembrolizumab and Olaparib Matching Placebos)
Olaparib 300 mg BIDMK-7339, LYNPARZA®Group B - Pembrolizumab 200 mg plus Olaparib 300 mg BID
Olaparib matching placeboGroup A - Pembrolizumab 200 mg
Etoposide 100 mg/m^2Group A - Pembrolizumab 200 mg
Platinum, investigator's choiceGroup A - Pembrolizumab 200 mg

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Group A - Pembrolizumab 200 mgExperimentalParticipants 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.
  • Pembrolizumab 200 mg
  • Pembrolizumab 400 mg
  • Olaparib matching placebo
  • Etoposide 100 mg/m^2
  • Platinum, investigator's choice
Group B - Pembrolizumab 200 mg plus Olaparib 300 mg BIDExperimentalParticipants 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.
  • Pembrolizumab 200 mg
  • Pembrolizumab 400 mg
  • Olaparib 300 mg BID
  • Etoposide 100 mg/m^2
  • Platinum, investigator's choice
Group C (Pembrolizumab and Olaparib Matching Placebos)Placebo ComparatorParticipants 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.
  • Pembrolizumab placebo (saline)
  • Pembrolizumab placebo (saline)
  • Olaparib matching placebo
  • Etoposide 100 mg/m^2
  • Platinum, investigator's choice

Eligibility 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 the time needed to
             eliminate each study intervention.

         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
             the time needed to eliminate each study intervention.

        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.
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Number of Participants Experiencing an Adverse Events (AEs)
Time Frame:Up to approximately 82 months
Safety Issue:
Description: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.
Measure:Number of Participants Discontinuing Study Treatment Due to Adverse Events (AEs)
Time Frame:Up to approximately 82 months
Safety Issue:
Description: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.
Measure:Objective Response (OR): Complete Response (CR) or Partial Response (PR)
Time Frame:Up to approximately 82 months
Safety Issue:
Description:Percentage of participants in the analysis population who have a best overall response of either confirmed CR or a PR per RECIST 1.1.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure:Change from Baseline at Cycle 1 in EORTC QLQ-LC13 Chest Pain (Item 10) Scale Score
Time Frame:Baseline and 82 months post randomization
Safety Issue:
Description: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.
Measure:Change from Baseline at Cycle 1 in EORTC QLQ-C30 Dyspnea (Item 8) Scale Score
Time Frame:Baseline and 82 months post randomization
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure:Time to True Deterioration (TTD) in Cough (LC13/Item 1) Scale Score
Time Frame:Up to approximately 82 months post randomization
Safety Issue:
Description: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.
Measure:Time to True Deterioration (TTD) in Chest Pain (LC13/Item 10) Scale Score
Time Frame:Up to approximately 82 months post randomization
Safety Issue:
Description: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.
Measure:Time to True Deterioration (TTD) in EORTC QLQ-C30 Dyspnea (Item 8) Scale Score
Time Frame:Up to approximately 82 months post randomization
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure:Overall Survival (OS) assessed by programmed cell death ligand 1 (PD-L1) expression levels
Time Frame:Up to approximately 82 months
Safety Issue:
Description:Overall Survival: the time from randomization to death due to any cause, analyzed by programmed cell death ligand 1 (PD-L1) expression levels.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Merck Sharp & Dohme Corp.

Trial Keywords

  • Programmed Cell Death-1 (PD1, PD-1)
  • Programmed Death-Ligand 1 (PDL1, PD-L1)
  • Pembrolizumab
  • Olaparib

Last Updated

August 26, 2021