Study of Pembrolizumab/Vibostolimab Coformulation (MK-7684A) in Combination With Chemotherapy Versus Pembrolizumab Plus Chemotherapy in Participants With Metastatic Non-Small Cell Lung Cancer (MK-7684A-007/KEYVIBE-007)

Study Overview
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Brief Summary
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The primary hypothesis is that pembrolizumab/vibostolimab (MK-7684A) in combination with chemotherapy is superior to pembrolizumab in combination with chemotherapy with respect to overall survival (OS) in treatment-naïve metastatic participants with non-small cell lung cancer (NSCLC).

Official Title
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A Randomized, Double-Blind, Phase 3 Study of MK-7684A in Combination With Chemotherapy Versus Pembrolizumab Plus Chemotherapy as First Line Treatment for Participants With Metastatic Non-Small Cell Lung Cancer

Conditions
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Metastatic Non-Small Cell Lung Cancer

Intervention / Treatment
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* Biological: Pembrolizumab/Vibostolimab
* Drug: Carboplatin
* Drug: Cisplatin
* Drug: Paclitaxel
* Drug: Nab-paclitaxel
* Drug: Pemetrexed
* Biological: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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The main inclusion and exclusion criteria include but are not limited to the following: Inclusion Criteria: A histologically or cytologically confirmed diagnosis of Stage IV squamous or non-squamous NSCLC. Has not received prior systemic treatment for metastatic NSCLC. Has measurable disease based on RECIST 1.1, as determined by the local site assessment. Has a life expectancy of at least 3 months. Males: Use contraception unless confirmed to be azoospermic; Females: Women of childbearing potential use highly effective contraceptive method. Exclusion Criteria: Known additional malignancy that is progressing or has required active treatment within the past 3 years. Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Severe hypersensitivity to vibostolimab, pembrolizumab, chemotherapy components, and/or any of its excipients. 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 before the first dose of study medication. Active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed. History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease. Has an active infection requiring systemic therapy. Has a known history of human immunodeficiency virus (HIV), Hepatitis B or/and Hepatitis C virus. Received prior systemic anticancer therapy for metastatic disease. Received a live or live attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed. History of allogeneic tissue/solid organ transplant. Is unable to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), other than an aspirin dose ≤1.3 g/day, for a 5-day period (8-day period for long-acting agents, such as piroxicam). Is unable or unwilling to take folic acid or vitamin B12 supplementation. Currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention.

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pembrolizumab/Vibostolimab + Carboplatin + Cisplatin + Paclitaxel + Nab-paclitaxel + Pemetrexed<br>Participants receive pembrolizumab/vibostolimab (co-formulation of 200mg pembrolizumab and 200 mg vibostolimab) via intravenous (IV) infusion on Day 1 of each cycle (cycle length = 3 weeks) for up to 35 cycles (up to  2 years) PLUS paclitaxel IV (on Day 1 of each cycle) OR nab-paclitaxel IV (on Days 1, 8, and 15 of each cycle) and carboplatin IV (on Day 1 of each cycle) for 4 cycles for Squamous NSCLC; PLUS carboplatin IV (on Day 1 of each cycle) Or cisplatin IV (on Day 1 of each cycle) for 4 cycles and pemetrexed IV (on Day 1 of each cycle) until progression, intolerable adverse events, or participant/physician decision for Non-squamous. | Biological: Pembrolizumab/Vibostolimab<br>* Co-formulation of pembrolizumab 200 mg/20 mL vial and vibostolimab 200 mg administered as IV infusion for up to 35 administrations<br>* Other names: MK-7684A;Drug: Carboplatin<br>* Carboplatin 10 mg/ml administered as IV infusion Q3W for 4 administrations<br>* Other names: PARAPLATIN®, Paraplatin NovaPlus ®;Drug: Cisplatin<br>* Cisplatin 1 mg/ml administered as IV infusion Q3W for 4 administrations<br>* Other names: Platinol-AQ®;Drug: Paclitaxel<br>* Paclitaxel 6mg/ml administered as IV infusion Q3W for 4 administrations<br>* Other names: TAXOL®, ONXOL®;Drug: Nab-paclitaxel<br>* Nab-paclitaxel 100 mg/vial administered as IV infusion Days 1, 8, and 15 of each 21-day cycle for 4 administrations<br>* Other names: ABRAXANE®;Drug: Pemetrexed<br>* Pemetrexed 500 mg/vial administered as IV infusion Q3W until progression, intolerable adverse event (AE), or participant or physician decision<br>* Other names: Alimta®;|
| Active Comparator: Pembrolizumab + Carboplatin + Cisplatin + Paclitaxel + Nab-paclitaxel + Pemetrexed<br>Participants receive pembrolizumab 200 mg via IV infusion on Day 1 of each cycle (cycle length = 3 weeks) for up to 35 cycles (up to  2 years) PLUS paclitaxel IV (on Day 1 of each cycle) OR nab-paclitaxel IV (on Days 1, 8, and 15 of each cycle) and carboplatin IV (on Day 1 of each cycle) for 4 cycles for Squamous NSCLC; PLUS carboplatin IV (on Day 1 of each cycle) Or cisplatin IV (on Day 1 of each cycle) for 4 cycles and pemetrexed IV (on Day 1 of each cycle) until progression, intolerable adverse events, or participant/physician decision for Non-squamous. | Drug: Carboplatin<br>* Carboplatin 10 mg/ml administered as IV infusion Q3W for 4 administrations<br>* Other names: PARAPLATIN®, Paraplatin NovaPlus ®;Drug: Cisplatin<br>* Cisplatin 1 mg/ml administered as IV infusion Q3W for 4 administrations<br>* Other names: Platinol-AQ®;Drug: Paclitaxel<br>* Paclitaxel 6mg/ml administered as IV infusion Q3W for 4 administrations<br>* Other names: TAXOL®, ONXOL®;Drug: Nab-paclitaxel<br>* Nab-paclitaxel 100 mg/vial administered as IV infusion Days 1, 8, and 15 of each 21-day cycle for 4 administrations<br>* Other names: ABRAXANE®;Drug: Pemetrexed<br>* Pemetrexed 500 mg/vial administered as IV infusion Q3W until progression, intolerable adverse event (AE), or participant or physician decision<br>* Other names: Alimta®;Biological: Pembrolizumab<br>* Pembrolizumab 25 mg/mL administered as IV infusion Q3W for up to 35 administrations<br>* Other names: MK-3475, KEYTRUDA®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS is defined as the time from randomization to the date of death due to any cause. | Up to approximately 40 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first as assessed by Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1). PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by blinded independent central review (BICR) will be presented. | Up to approximately 40 months | 
| Objective Response Rate (ORR) | ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage of participants who experience CR or PR as assessed by BICR will be presented. | Up to approximately 40 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) | Change from baseline in the score of EORTC QLQ-C30 Items 29 and 30 will be presented. The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. 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 quality of life 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 40 months | 
| Change from Baseline in Physical Functioning (Items 1-5) Combined Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Change from baseline in the score of EORTC QLQ-C30 Items 1-5 will be presented. The EORTC QLQ-C30 is a cancer specific health-related quality-of life (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 40 months | 
| Change from Baseline for Role Functioning Combined (Items 6 and 7) Score on the EORTC QLQ-C30 | Change from baseline in the score of EORTC QLQ-C30 Items 6-7 will be presented. The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 2 questions about their role 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 40 months | 
| Change from Baseline in Dyspnea Score (Item 8) on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Change from baseline in the score of EORTC QLQ-C30 Item 8 will be presented. The EORTC QLQ-C30 is a cancer specific health-related quality-of life (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 40 months | 
| Change from Baseline in Cough Score (Item 31) on the European Organization for Research and Treatment of Cancer Quality of Life Lung Cancer-Specific Questionnaire Module (EORTC QLQ-LC13) | Change from baseline in the score of EORTC QLQ-C13 Item 31 will be presented. The EORTC QLQ-C13 is a lung cancer specific health-related quality-of life (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 40 months | 
| Change from Baseline in Chest Pain Score (Item 40) on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Change from baseline in the score of EORTC QLQ-C13 Item 40 will be presented. The EORTC QLQ-C13 is a lung cancer specific health-related quality-of life (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 40 months | 
| Time to Deterioration (TTD) 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) | TTD in the score of EORTC QLQ-C30 Items 29 and 30 will be presented. The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. 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 quality of life 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. | Up to approximately 40 months | 
| TTD in Physical Functioning (Items 1-5) Combined Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | TTD in the score of EORTC QLQ-C30 Items 1-5 will be presented. The EORTC QLQ-C30 is a cancer specific health-related quality-of life (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. | Up to approximately 40 months | 
| TTD in Role Functioning (Items 6 and 7) Combined Score on the EORTC QLQ-C30 | TTD in the score of EORTC QLQ-C30 Items 6-7 will be presented. The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 2 questions about their role functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Higher scores indicate a worse level of function. | Up to approximately 40 months | 
| TTD in Dyspnea Score (Item 8) on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | TTD in the score of EORTC QLQ-C30 Item 8 will be presented. The EORTC QLQ-C30 is a cancer specific health-related quality-of life (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. | Up to approximately 40 months | 
| TTD in Cough Score (Item 31) on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | TTD in the score of EORTC QLQ-C13 Item 31 will be presented. The EORTC QLQ-C13 is a lung cancer specific health-related quality-of life (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. | Up to approximately 40 months | 
| TTD in Chest Pain Score (Item 40) on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | TTD in the score of EORTC QLQ-C13 Item 40 will be presented. The EORTC QLQ-C13 is a lung cancer specific health-related quality-of life (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. | Up to approximately 40 months | 
| Number of Participants Who Experienced One or More Adverse Events (AEs) | The number of participants who experienced an adverse event (AE) will be presented. An AE is defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. | Up to approximately 40 months | 
| Number of Participants Who Discontinued Study Intervention Due to an AE | The number of participants who discontinue study intervention due to an adverse event (AE) will be presented. An AE is defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. | Up to approximately 40 months | 
| Duration of Response (DOR) | For participants who demonstrate a Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. The DOR as assessed by blinded independent central review will be presented. | Up to approximately 40 months |