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)

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Small Cell Lung Carcinoma

Intervention / Treatment
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* Biological: Pembrolizumab/Vibostolimab Co-Formulation
* Drug: Saline placebo
* Drug: Etoposide
* Drug: Cisplatin
* Biological: Atezolizumab
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pembrolizumab/Vibostolimab<br>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<br>* 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.<br>* Other names: MK-7684A;Drug: Saline placebo<br>* Saline solution administered via IV infusion on Cycle 1 (and Q3W as needed beyond Cycle 1)<br>Drug: Etoposide<br>* Etoposide 100 mg/m^2 administered via IV infusion Q3W on Days 1 2, 3 of each cycle for up to 4 cycles<br>Drug: Cisplatin<br>* Cisplatin 75 mg/m^2 administered via IV infusion Q3W on Day 1 of each cycle for up to 4 cycles.<br>* Other names: PLATINOL-AQ®;Drug: Carboplatin<br>* Carboplatin AUC 5 mg/mL/min administered via IV infusion Q3W on Day 1 of each cycle for up to 4 cycles.<br>* Other names: PARAPLATIN®;|
| Active Comparator: Atezolizumab<br>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<br>* Saline solution administered via IV infusion on Cycle 1 (and Q3W as needed beyond Cycle 1)<br>Drug: Etoposide<br>* Etoposide 100 mg/m^2 administered via IV infusion Q3W on Days 1 2, 3 of each cycle for up to 4 cycles<br>Drug: Cisplatin<br>* Cisplatin 75 mg/m^2 administered via IV infusion Q3W on Day 1 of each cycle for up to 4 cycles.<br>* Other names: PLATINOL-AQ®;Biological: Atezolizumab<br>* Atezolizumab 1200 mg administered via IV infusion Q3W on Day 1 of each cycle until discontinuation criteria are met.<br>* Other names: TECENTRIQ®;Drug: Carboplatin<br>* Carboplatin AUC 5 mg/mL/min administered via IV infusion Q3W on Day 1 of each cycle for up to 4 cycles.<br>* Other names: PARAPLATIN®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Overall Survival (OS) is the time from randomization to the date of death due to any cause. | Up to approximately 37 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | 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. | Up to approximately 26 months | 
| Objective Response Rate (ORR) | 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). | Up to approximately 37 months | 
| Duration of Response (DOR) | 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. | Up to approximately 37 months | 
| Percentage of Participants Who Experienced an Adverse Event (AE) | 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. | Up to approximately 60 months | 
| Percentage of Participants Who Discontinued Study Treatment Due to an AE | 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. | Up to approximately 60 months | 
| 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) | 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. | Baseline and up to approximately 37 months | 
| Change from Baseline in Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ-C30 | 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. | Baseline and up to approximately 37 months | 
| Change from Baseline in Dyspnea Score (Item 8) on the EORTC QLQ-C30 | 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. | Baseline and up to approximately 37 months | 
| 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) | 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. | Baseline and up to approximately 37 months | 
| Change from Baseline in Chest Pain Score (Item 40) on the EORTC QLQ-LC13 | 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. | Baseline and up to approximately 37 months | 
| Time to True Deterioration (TTD) in the Global Health Status/Quality of Life (Items 29 and 30) Combined Score on the EORTC QLQ-C30 | 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. | Baseline and up to approximately 37 months | 
| TTD in Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ-C30 | 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. | Baseline and up to approximately 37 months | 
| TTD in Dyspnea Score (Item 8) on the EORTC QLQ-C30 | 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. | Baseline and up to approximately 37 months | 
| TTD in Cough Score (Item 31) on the EORTC QLQ-LC13 | 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. | Baseline and up to approximately 37 months | 
| TTD in Chest Pain Score (Item 40) on the EORTC QLQ-LC13 | 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. | Baseline and up to approximately 37 months |