Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Pembrolizumab/Vibostolimab (MK-7684A) or Atezolizumab in Combination With Chemotherapy in First Line Treatment of Extensive-Stage Small Cell Lung Cancer (MK-7684A-008, KEYVIBE-008)

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: NCT05224141
Recruitment Status : Recruiting
First Posted : February 4, 2022
Last Update Posted : August 11, 2022
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

Brief Summary:
This study will evaluate the combination of a fixed dose pembrolizumab/vibostolimab co-formulation (MK-7684A) with etoposide/platinum chemotherapy followed by MK-7684A compared to the combination of atezolizumab with etoposide/platinum chemotherapy followed by atezolizumab in the first-line treatment of Extensive-Stage Small Cell Lung Cancer (ES-SCLC). The primary hypothesis is, with respect to overall survival, MK-7684A in combination with the background therapy of etoposide/platinum followed by MK-7684A, is superior to atezolizumab in combination with the background therapy of etoposide/platinum followed by atezolizumab.

Condition or disease Intervention/treatment Phase
Small Cell Lung Carcinoma Biological: Pembrolizumab/Vibostolimab Co-Formulation Drug: Saline placebo Drug: Etoposide Drug: Cisplatin Biological: Atezolizumab Drug: Carboplatin Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 450 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-Blind Study of MK-7684A in Combination With Etoposide and Platinum Followed by MK-7684A vs Atezolizumab in Combination With Etoposide and Platinum Followed by Atezolizumab for the First-Line Treatment of Participants With Extensive-Stage Small Cell Lung Cancer
Actual Study Start Date : March 24, 2022
Estimated Primary Completion Date : May 8, 2025
Estimated Study Completion Date : June 7, 2027

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: Pembrolizumab/Vibostolimab
Participants will receive 4 cycles (each cycle is 3 weeks) of a fixed-dose coformulation of 200 mg pembrolizumab and 200 mg vibostolimab (MK-7684A) every 3 weeks (Q3W), in combination with 100 mg/m^2 etoposide, and platinum (Area Under the Curve (AUC) 5 mg/mL/min carboplatin or 75 mg/m^2 cisplatin) chemotherapy Q3W for a total of approximately 12 weeks. This will be followed by additional cycles of MK-7684A Q3W until any of the conditions for discontinuation are met. To maintain the blinding, saline placebo will be administered on cycle 1 day 1 and then Q3W as needed beyond cycle 1.
Biological: Pembrolizumab/Vibostolimab Co-Formulation
Pembrolizumab 200 mg plus vibostolimab 200 mg fixed dose coformulation administered via IV infusion Q3W on Day 1 of each cycle until discontinuation criteria are met.
Other Name: MK-7684A

Drug: Saline placebo
Saline solution administered via IV infusion on Cycle 1 (and Q3W as needed beyond Cycle 1)

Drug: Etoposide
Etoposide 100 mg/m^2 administered via IV infusion Q3W on Days 1 2, 3 of each cycle for up to 4 cycles

Drug: Cisplatin
Cisplatin 75 mg/m^2 administered via IV infusion Q3W on Day 1 of each cycle for up to 4 cycles.
Other Name: PLATINOL-AQ®

Drug: Carboplatin
Carboplatin AUC 5 mg/mL/min administered via IV infusion Q3W on Day 1 of each cycle for up to 4 cycles.
Other Name: PARAPLATIN®

Active Comparator: Atezolizumab
Participants will receive 4 cycles (each cycle is 3 weeks) of 1200 mg atezolizumab Q3W, in combination with 100 mg/m^2 etoposide and platinum (AUC 5 mg/mL/min carboplatin or 75 mg/m^2 cisplatin) chemotherapy Q3W for a total of approximately 12 weeks. This will be followed by additional cycles of atezolizumab Q3W until any of the conditions for discontinuation are met. To maintain the blinding, saline placebo will be administered on cycle 1 day 1 and then Q3W as needed beyond cycle 1.
Drug: Saline placebo
Saline solution administered via IV infusion on Cycle 1 (and Q3W as needed beyond Cycle 1)

Drug: Etoposide
Etoposide 100 mg/m^2 administered via IV infusion Q3W on Days 1 2, 3 of each cycle for up to 4 cycles

Drug: Cisplatin
Cisplatin 75 mg/m^2 administered via IV infusion Q3W on Day 1 of each cycle for up to 4 cycles.
Other Name: PLATINOL-AQ®

Biological: Atezolizumab
Atezolizumab 1200 mg administered via IV infusion Q3W on Day 1 of each cycle until discontinuation criteria are met.
Other Name: TECENTRIQ®

Drug: Carboplatin
Carboplatin AUC 5 mg/mL/min administered via IV infusion Q3W on Day 1 of each cycle for up to 4 cycles.
Other Name: PARAPLATIN®




Primary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: Up to approximately 37 months ]
    Overall Survival (OS) is the time from randomization to the date of death due to any cause.


Secondary Outcome Measures :
  1. Progression-Free Survival (PFS) [ Time Frame: Up to approximately 26 months ]
    Progression-Free Survival (PFS) is the time from randomization to the first documented disease progression (PD) or death due to any cause, whichever occurs first.

  2. Objective Response Rate (ORR) [ Time Frame: Up to approximately 37 months ]
    Objective Response Rate (ORR) is the percentage of participants who have a Complete Response (CR) (disappearance of all target lesions) or a Partial Response (PR) (at least a 30% decrease in the sum of diameters of target lesions).

  3. Duration of Response (DOR) [ Time Frame: Up to approximately 37 months ]
    Duration of Response (DOR) is the time from first documented evidence of CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions), until progressive disease (PD) or death.

  4. Percentage of Participants Who Experienced an Adverse Event (AE) [ Time Frame: Up to approximately 60 months ]
    An AE is 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.

  5. Percentage of Participants Who Discontinued Study Treatment Due to an AE [ Time Frame: Up to approximately 60 months ]
    An AE is 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.

  6. Change from Baseline in the Global Health Status/Quality of Life (Items 29 and 30) Combined Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) [ Time Frame: Baseline and up to approximately 37 months ]
    The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life (QoL) of individuals with cancer. Participant responses to Items 29 and 30 ("How would you rate your overall health during the past week?" and "How would you rate your overall QoL during the past week?") are scored on a 7-point scale (1=Very Poor to 7=Excellent). A higher score indicates a better overall outcome.

  7. Change from Baseline in Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ-C30 [ Time Frame: Baseline and up to approximately 37 months ]
    The EORTC QLQ-C30 is a cancer specific health-related QoL questionnaire. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Higher scores indicate a worse level of function.

  8. Change from Baseline in Dyspnea Score (Item 8) on the EORTC QLQ-C30 [ Time Frame: Baseline and up to approximately 37 months ]
    The EORTC QLQ-C30 is a cancer specific health-related QoL questionnaire. Participant response to the question "Were you short of breath?" is scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates a worse level of dyspnea.

  9. Change from Baseline in Cough Score (Item 31) on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13) [ Time Frame: Baseline and up to approximately 37 months ]
    The EORTC QLQ-LC13 is a lung cancer specific health-related QoL questionnaire. Participant response to the question "Have you coughed?" is scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates more frequent coughing.

  10. Change from Baseline in Chest Pain Score (Item 40) on the EORTC QLQ-LC13 [ Time Frame: Baseline and up to approximately 37 months ]
    EORTC QLQ-LC13 is a lung cancer specific health-related QoL questionnaire. Participant response to the question "Have you had pain in your chest?" is scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates a worse level of chest pain.

  11. Time to True Deterioration (TTD) in the Global Health Status/Quality of Life (Items 29 and 30) Combined Score on the EORTC QLQ-C30 [ Time Frame: Baseline and up to approximately 37 months ]
    The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the QoL of individuals with cancer. Participant responses to Items 29 and 30 ("How would you rate your overall health during the past week?" and "How would you rate your overall QoL during the past week?") are scored on a 7-point scale (1=Very Poor to 7=Excellent). A higher score indicates a better overall outcome. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline.

  12. TTD in Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ-C30 [ Time Frame: Baseline and up to approximately 37 months ]
    The EORTC QLQ-C30 is a cancer specific health-related QoL questionnaire. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Higher scores indicate a worse level of function. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline.

  13. TTD in Dyspnea Score (Item 8) on the EORTC QLQ-C30 [ Time Frame: Baseline and up to approximately 37 months ]
    The EORTC QLQ-C30 is a cancer specific health-related QoL questionnaire. Participant response to the question "Were you short of breath?" is scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates a worse level of dyspnea. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline.

  14. TTD in Cough Score (Item 31) on the EORTC QLQ-LC13 [ Time Frame: Baseline and up to approximately 37 months ]
    The EORTC QLQ-LC13 is a lung cancer specific health-related QoL questionnaire. Participant response to the question "Have you coughed?" is scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates more frequent coughing. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline.

  15. TTD in Chest Pain Score (Item 40) on the EORTC QLQ-LC13 [ Time Frame: Baseline and up to approximately 37 months ]
    The EORTC QLQ-LC13 is a lung cancer specific health-related QoL questionnaire. Participant response to the question "Have you had pain in your chest?" is scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates a worse level of chest pain. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline.



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.


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

Inclusion Criteria:

  • Has histologically or cytologically confirmed diagnosis of ES-SCLC in need of first-line therapy
  • Has ES-SCLC defined as Stage IV (T any, N any, M1a/b/c) by the American Joint Committee on Cancer, Eighth Edition or T3-T4 due to multiple lung nodules that are too extensive or have tumor/nodal volume that is too large to be encompassed in a tolerable radiation plan
  • Males agree to use contraception, refrain from donating sperm, and abstain from heterosexual intercourse
  • Females are not pregnant or breastfeeding, is not a woman of childbearing potential (WOCBP) or is a WOCBP who uses a highly effective contraceptive method, or is abstinent from heterosexual intercourse
  • Has measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
  • Has a predicted life expectancy of >3 months

Exclusion Criteria:

  • Is considered a poor medical risk due to a serious, uncontrolled medical disorder or non-malignant systemic disease
  • Has received prior treatment for Small Cell Lung Cancer (SCLC)
  • Is expected to require any other form of antineoplastic therapy for SCLC while on study
  • Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
  • Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication
  • Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Has a history of severe hypersensitivity reaction (≥Grade 3) to any study intervention and/or any of its excipients
  • Has an active autoimmune disease that has required systemic treatment in past 2 years
  • Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
  • Has a known history of, or active, neurologic paraneoplastic syndrome
  • Has an active infection requiring systemic therapy
  • Has a known history of human immunodeficiency virus (HIV) infection
  • Has a known history of Hepatitis B or known active Hepatitis C virus infection
  • Has had an allogenic tissue/solid organ transplant
  • Has had major surgery within prior 3 weeks or has not recovered adequately from toxicity and/or complications from an intervention prior to receiving the first dose of study intervention
  • Has symptomatic ascites or pleural effusion

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): NCT05224141


Contacts
Layout table for location contacts
Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

Locations
Show Show 67 study locations
Sponsors and Collaborators
Merck Sharp & Dohme LLC
Investigators
Layout table for investigator information
Study Director: Medical Director Merck Sharp & Dohme LLC
Additional Information:
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier: NCT05224141    
Other Study ID Numbers: 7684A-008
MK-7684A-008 ( Other Identifier: Merck )
KEYVIBE-008 ( Other Identifier: Merck )
jRCT2021220008 ( Registry Identifier: jRCT )
2021-005034-42 ( EudraCT Number )
First Posted: February 4, 2022    Key Record Dates
Last Update Posted: August 11, 2022
Last Verified: August 2022
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

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Small Cell Lung Carcinoma
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carboplatin
Pembrolizumab
Etoposide
Atezolizumab
Antineoplastic Agents
Antineoplastic Agents, Immunological
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action