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)

Phase 3TerminatedNCT05226598

Merck Sharp & Dohme LLC739 enrolled

Overview

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 participants with programmed cell death-ligand 1 (PD-L1) tumor proportion score (TPS) ≥1%.

Effective as of Amendment 5, Participants receiving coformulation of pembrolizumab/vibostolimab plus chemotherapy will be transitioned to standard of care (SOC, pembrolizumab plus chemotherapy). Participants with access to approved standard of care (SOC) should be considered for discontinuation from the study. Those benefiting from pembrolizumab plus chemotherapy, but unable to access it as SOC outside the study, may continue on study and receive treatment with pembrolizumab plus chemotherapy until discontinuation criteria are met.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

739

Conditions

Metastatic Non-Small Cell Lung Cancer

Interventions

Pembrolizumab/VibostolimabBIOLOGICAL

Co-formulation of pembrolizumab 200 mg/20 mL vial and vibostolimab 200 mg administered as IV infusion for up to 35 administrations

CarboplatinDRUG

Carboplatin 10 mg/ml administered as IV infusion Q3W for 4 administrations

CisplatinDRUG

Cisplatin 1 mg/ml administered as IV infusion Q3W for 4 administrations

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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 MK-7684, MK-7684A, 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, except replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) * 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

Locations (149)

Outcomes

Primary Outcomes

Overall Survival (OS) in Participants With Programmed Cell Death-Ligand 1 (PD-L1) Tumor Proportion Score (TPS) ≥1%

OS is defined as the time from the date of randomization to death due to any cause. The OS is reported for all participants with PD-L1 positive tumors (PD-L1 TPS≥1%). The OS was calculated using the product-limit (Kaplan-Meier) method for censored data.

Time frame: Up to approximately 29 months

Secondary Outcomes

Overall Survival (OS) in All Participants

OS is defined as the time from the date of randomization to death due to any cause. The OS is reported for all randomized participants. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data.

Time frame: Up to approximately 29 months

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) was planned to be presented.

Time frame: Up to approximately 29 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 blinded independent central review (BICR) was planned to be presented.

Time frame: Up to approximately 29 months

Duration of Response (DOR)

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Paclitaxel 6mg/ml administered as IV infusion Q3W for 4 administrations

Nab-paclitaxelDRUG

Nab-paclitaxel 100 mg/vial administered as IV infusion Days 1, 8, and 15 of each 21-day cycle for 4 administrations

PemetrexedDRUG

Pemetrexed 500 mg/vial administered as IV infusion Q3W until progression, intolerable adverse event (AE), or participant or physician decision

PembrolizumabBIOLOGICAL

Pembrolizumab 25 mg/mL administered as IV infusion Q3W for up to 35 administrations

UCHealth Memorial Hospital-Heme Onc ( Site 0003)

Colorado Springs, Colorado, United States

University of Colorado Health - Harmony-Cancer Care and Hematology - Ft. Collins ( Site 0031)

Fort Collins, Colorado, United States

Mayo Clinic in Florida ( Site 0022)

Jacksonville, Florida, United States

Mount Sinai Hospital ( Site 0011)

Chicago, Illinois, United States

University of Chicago Medical Center ( Site 0015)

Chicago, Illinois, United States

New England Cancer Specialists ( Site 0008)

Scarborough, Maine, United States

Cancer and Hematology Centers of Western Michigan ( Site 0002)

Grand Rapids, Michigan, United States

Mayo Clinic in Rochester, Minnesota ( Site 0030)

Rochester, Minnesota, United States

Stony Brook University-Cancer Center ( Site 0013)

Stony Brook, New York, United States

Lancaster General Hospital - Ann B Barshinger Cancer Institute ( Site 0012)

Lancaster, Pennsylvania, United States

...and 139 more locations

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 BICR was planned to be presented.

Time frame: Up to approximately 29 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 was planned to 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.

Time frame: Baseline and Up to approximately 29 months

Change From Baseline in Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ-C30

Change from baseline in the score of EORTC QLQ-C30 Items 1-5 was planned to 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.

Time frame: Baseline and Up to approximately 29 months

Change From Baseline for Role Functioning (Items 6 and 7) Combined Score on the EORTC QLQ-C30

Change from baseline in the score of EORTC QLQ-C30 Items 6-7 was planned to 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.

Time frame: Baseline and up to approximately 29 months

Change From Baseline in Dyspnea Score (Item 8) on the EORTC QLQ-C30

Change from baseline in the score of EORTC QLQ-C30 Item 8 was planned to 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.

Time frame: Baseline and Up to approximately 29 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-LC13 Item 31 was planned to be presented. The EORTC QLQ-LC13 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.

Time frame: Baseline and Up to approximately 29 months

Change From Baseline in Chest Pain Score (Item 40) on the EORTC QLQ- LC13

Change from baseline in the score of EORTC QLQ-LC13 Item 40 was planned to be presented. The EORTC QLQ-LC13 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.

Time frame: Baseline and Up to approximately 29 months

Time to Deterioration (TTD) in the Global Health Status/Quality of Life (Items 29 and 30) Combined Score on the EORTC QLQ-C30

TTD in the score of EORTC QLQ-C30 Items 29 and 30 was planned to 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.

Time frame: Up to approximately 29 months

TTD in Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ- C30

TTD in the score of EORTC QLQ-C30 Items 1-5 was planned to 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.

Time frame: Up to approximately 29 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 was planned to 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. 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.

Time frame: Up to approximately 29 months

TTD in Dyspnea Score (Item 8) on the EORTC QLQ-C30

TTD in the score of EORTC QLQ-C30 Item 8 was planned to 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.

Time frame: Up to approximately 29 months

TTD in Cough Score (Item 31) on the EORTC QLQ-LC13

TTD in the score of EORTC QLQ-LC13 Item 31 was planned to be presented. The EORTC QLQ-LC13 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.

Time frame: Up to approximately 29 months

TTD in Chest Pain Score (Item 40) on the EORTC QLQ-LC13

TTD in the score of EORTC QLQ-LC13 Item 40 was planned to be presented. The EORTC QLQ-LC13 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.

Time frame: Up to approximately 29 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.

Time frame: Up to approximately 46 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.

Time frame: Up to approximately 46 months