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)

• ClinicalTrials.gov Identifier: NCT05224141
• Recruitment Status: Recruiting
• First Posted: February 4, 2022
• Last Update Posted: March 7, 2023
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

Tracking Information

• First Submitted Date: January 25, 2022
• First Posted Date: February 4, 2022
• Last Update Posted Date: March 7, 2023
• Actual Study Start Date: March 24, 2022
• Estimated Primary Completion Date: May 8, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 25, 2022)

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 25, 2022)

• 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.
• 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).
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Small Cell Lung Carcinoma

Intervention

• 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®
• 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®

Study Arms

• 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.
  Interventions:

  • Biological: Pembrolizumab/Vibostolimab Co-Formulation
  • Drug: Saline placebo
  • Drug: Etoposide
  • Drug: Cisplatin
  • Drug: Carboplatin
• 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.
  Interventions:

  • Drug: Saline placebo
  • Drug: Etoposide
  • Drug: Cisplatin
  • Biological: Atezolizumab
  • Drug: Carboplatin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 25, 2022): 450
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 7, 2027
• Estimated Primary Completion Date: May 8, 2025 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: Argentina, Australia, Austria, Canada, China, Finland, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Lithuania, Mexico, Netherlands, Poland, Portugal, Romania, Spain, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: 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 )
• 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

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

• Current Responsible Party: Merck Sharp & Dohme LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Merck Sharp & Dohme LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme LLC

• PRS Account: Merck Sharp & Dohme LLC
• Verification Date: March 2023