Study of Pembrolizumab/Vibostolimab (MK-7684A) in Combination With Concurrent Chemoradiotherapy Followed by Pembrolizumab/Vibostolimab Versus Concurrent Chemoradiotherapy Followed by Durvalumab in Participants With Stage III Non-small Cell Lung Cancer (MK-7684A-006/KEYVIBE-006)

Carcinoma, Non-Small-Cell Lung Clinical Trial

Official title:

Open-label Phase 3 Study of MK-7684A (Coformulation of Vibostolimab With Pembrolizumab) in Combination With Concurrent Chemoradiotherapy Followed by MK-7684A Versus Concurrent Chemoradiotherapy Followed by Durvalumab in Participants With Unresectable, Locally Advanced, Stage III NSCLC

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05298423
• Other study ID #: 7684A-006
• Secondary ID: MK-7684A-006KEYV
• Status: Recruiting
• Phase: Phase 3
• Start date: May 3, 2022
• Est. completion date: September 4, 2029

Study information

• Verified date: April 2024
• Source: Merck Sharp & Dohme LLC
• Contact: Toll Free Number
• Phone: 1-888-577-8839
• Email: Trialsites[@]merck.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is to evaluate the safety and efficacy of pembrolizumab/vibostolimab (MK-7684A) in combination with concurrent chemoradiotherapy (cCRT) followed by pembrolizumab/vibostolimab versus cCRT followed by durvalumab in participants with unresectable, locally advanced, stage III Non-small Cell Lung Cancer (NSCLC). The primary hypotheses are that pembrolizumab/vibostolimab with cCRT followed by pembrolizumab/vibostolimab is superior to cCRT followed by durvalumab with respect to the following: - progression free survival (PFS) per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 by blinded independent central review (BICR) in participants with programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) ≥1% and PD-L1 all comer participants. - overall survival (OS) in participants with PD-L1 TPS ≥1% and PD-L1 all comer participants.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 784
• Est. completion date: September 4, 2029
• Est. primary completion date: September 1, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

The main inclusion and exclusion criteria include but are not limited to the following:

Inclusion Criteria

• Has pathologically (histologically or cytologically) confirmed diagnosis of NSCLC.
• Has Stage IIIA, IIIB, or IIIC NSCLC by American Joint Committee on Cancer Version 8
• Is determined to have unresectable, Stage III NSCLC as documented by a multidisciplinary tumor board or by the treating physician in consultation with a thoracic surgeon
• Has no evidence of metastatic disease, indicating Stage IV NSCLC, in whole-body fluorodeoxyglucose (FDG)-positron emission tomography (PET) or FDG-PET/ computed tomography (CT) and CT or magnetic resonance imaging (MRI) scans of diagnostic quality of chest, abdomen, pelvis and brain
• Has measurable disease as defined by RECIST 1.1, with at least 1 lesion being appropriate for selection as a target lesion, as determined by local site investigator/radiology review
• Has not received prior treatment (chemotherapy, targeted therapy, or radiotherapy) for their Stage III NSCLC
• Has provided tumor tissue sample (tissue biopsy [core, incisional, or excisional])
• Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 assessed within 7 days prior to the first administration of study intervention
• Has a life expectancy of at least 6 months Exclusion Criteria
• Has small cell lung cancer (SCLC) or tumors with the presence of small cell elements. Mixed squamous/nonsquamous tumors are eligible
• Has received prior radiotherapy to the thorax, including radiotherapy to the esophagus, mediastinum, or for breast cancer
• Has received major surgery (with the exception of replacement of vascular access) within 4 weeks before randomization. If the participant had a major operation, the participant must have recovered adequately from the procedure and/or any complications from the operation before starting study intervention
• Is expected to require any other form of antineoplastic therapy, while on study
• Has received colony-stimulating factors (e.g., Granulocyte Colony-Stimulating Factor [G-CSF], Granulocyte Macrophage Colony-Stimulating Factor [GM-CSF], or recombinant erythropoietin) within 28 days prior to the first dose of study intervention
• Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
• Is 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
• Has a 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 prior to the first dose of study medication
• Has a known additional malignancy that is progressing or has required active treatment within the past 5 years
• 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 an active infection requiring systemic therapy
• Has a known history of human immunodeficiency virus (HIV) infection
• Has a known history of Hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV ribonucleic acid [RNA] qualitative is detected) infection
• Has had an allogenic tissue/solid organ transplant

Pemetrexed-specific Criteria:

• Is unable to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), other than an aspirin dose =1.3 grams per day, for at least 2 days (5 days for long-acting agents [for example, piroxicam]) before, during, and for at least 2 days after administration of pemetrexed
• Is unable/unwilling to take folic acid, vitamin B12, and dexamethasone

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung

Intervention

Biological:
• pembrolizumab/vibostolimab
Administered as an intravenous (IV) infusion
• durvalumab
Administered as an IV infusion

Drug:
• cisplatin
Administered as an IV infusion
• pemetrexed
Administered as an IV infusion
• etoposide
Administered as an IV infusion
• carboplatin
Administered as an IV infusion
• paclitaxel
Administered as an IV infusion

Radiation:
• thoracic radiotherapy
Administered as an external beam radiation

Locations

Country	Name	City	State
Australia	Ballarat Health Services-Medical Oncology ( Site 0002)	Ballarat Central	Victoria
Australia	Canberra Hospital ( Site 0010)	Canberra	Australian Capital Territory
Australia	Frankston Hospital-Oncology and Haematology ( Site 0009)	Frankston	Victoria
Australia	Icon Cancer Centre Hobart ( Site 0003)	Hobart	Tasmania
Australia	St Vincent's Hospital-Oncology Clinical Trials ( Site 0005)	Melbourne	Victoria
Brazil	Hospital Nossa Senhora da Conceição ( Site 0111)	Porto Alegre	Rio Grande Do Sul
Brazil	Instituto de Educação, Pesquisa e Gestão em Saúde ( Site 0105)	Rio de Janeiro
Brazil	A. C. Camargo Cancer Center-CAPEC ( Site 0102)	Sao Paulo
Chile	Biocenter ( Site 0208)	Concepción	Biobio
Chile	Bradfordhill ( Site 0200)	Santiago	Region M. De Santiago
Chile	Centro de Oncología de Precisión ( Site 0209)	Santiago	Region M. De Santiago
Chile	FALP-UIDO ( Site 0205)	Santiago	Region M. De Santiago
Chile	James Lind Centro de Investigación del Cáncer ( Site 0202)	Temuco	Araucania
Chile	ONCOCENTRO APYS-ACEREY ( Site 0203)	Viña del Mar	Valparaiso
China	Beijing Cancer hospital-intrathoratic deparmtment II ( Site 0328)	Beijing	Beijing
China	Beijing Cancer hospital-Oncology Radiotherapy Department ( Site 0309)	Beijing	Beijing
China	Beijing Peking Union Medical College Hospital-pneumology department ( Site 0300)	Beijing	Beijing
China	Jilin Cancer Hospital-oncology department ( Site 0319)	Changchun	Jilin
China	Hunan Cancer Hospital ( Site 0307)	Changsha	Hunan
China	Xiangya Hospital Central South University-Oncology department ( Site 0310)	Changsha	Hunan
China	West China Hospital of Sichuan University ( Site 0324)	Cheng Du	Sichuan
China	Army Medical Center of People's Liberation Army-Oncology Department ( Site 0321)	Chongqing	Chongqing
China	Fujian Provincial Cancer Hospital ( Site 0316)	Fuzhou	Fujian
China	Fujian Medical University Union Hospital-1 Bingfanglou ( Site 0330)	Fuzhou Fujian	Fujian
China	Southern Medical University Nanfang Hospital-Department of Oncology ( Site 0336)	Guangzhou	Guangdong
China	Hangzhou Cancer Hospital-Medical Oncology ( Site 0302)	Hangzhou	Zhejiang
China	The Second Affiliated hospital of Zhejiang University school of medicine ( Site 0301)	Hangzhou	Zhejiang
China	Zhejiang Cancer Hospital ( Site 0308)	Hangzhou	Zhejiang
China	Shandong Provincial Hospital ( Site 0326)	Jinan	Shandong
China	Qingdao Central Hospital-Endocrinology ( Site 0332)	Qingdao	Shandong
China	Fudan University Shanghai Cancer Center ( Site 0304)	Shanghai	Shanghai
China	Shanghai Chest Hospital-Radiotherapy Department ( Site 0306)	Shanghai	Shanghai
China	Shanghai Pulmonary Hospital-Radiotherapy department ( Site 0335)	Shanghai	Shanghai
China	Fourth Hospital of Hebei Medical University ( Site 0331)	Shijiazhuang	Hebei
China	The Second Affiliated Hospital of Soochow University ( Site 0314)	Suzhou	Jiangsu
China	Shanxi Cancer Hospital-Pulmonology ( Site 0322)	Taiyuan	Shanxi
China	Tianjin Medical University Cancer Institute and Hospital-radiotherapy ( Site 0329)	Tianjin	Tianjin
China	Hubei Cancer Hospital ( Site 0311)	Wuhan	Hubei
China	Wuhan Union Hospital Cancer Center-Cancer Center ( Site 0315)	Wuhan	Hubei
China	The First Affiliated hospital of Xiamen University-oncology ( Site 0317)	Xiamen	Fujian
China	Henan Cancer Hospital ( Site 0333)	Zhengzhou	Henan
China	Affiliated Hospital of Jiangsu University ( Site 0305)	Zhenjiang	Jiangsu
Costa Rica	CIMCA ( Site 0501)	San José	San Jose
Costa Rica	PROCLINICAL Pharma ( Site 0504)	San José	San Jose
Costa Rica	Hospital Metropolitano - Sede Lindora ( Site 0503)	Santa Ana	San Jose
Dominican Republic	Onconet ( Site 3002)	Distrito Nacional	Santo Domingo
Dominican Republic	Instituto de Oncologia ( Site 3003)	Santo Domingo	Distrito Nacional
Germany	Charité Campus Virchow-Klinikum-Department of Infectious Diseases and Pulmonary Medicine ( Site 0603	Berlin
Germany	Klinikum Chemnitz-Klinik für Innere Medizin IV ( Site 0607)	Chemnitz	Sachsen
Germany	LungenClinic Grosshansdorf-Onkologie ( Site 0602)	Grosshansdorf	Schleswig-Holstein
Germany	Universitaetsklinikum Schleswig-Holstein Campus Kiel-Medizinische Klinik II, Hämatologie und Onkolo	Kiel	Schleswig-Holstein
Greece	Alexandra General Hospital of Athens-ONCOLOGY DEPT. ( Site 0706)	Athens	Attiki
Greece	Errikos Dunant Hospital Center-Second Department of Oncology and Clinical Trials Unit ( Site 0703)	Athens	Attiki
Greece	Metropolitan Hospital ( Site 0702)	Athens	Attiki
Greece	Sotiria Thoracic Diseases Hospital of Athens ( Site 0704)	Athens	Attiki
Greece	University General Hospital of Heraklion-Internal Medicine-Oncology ( Site 0700)	Heraklion	Irakleio
Greece	General Oncology Hospital of Kifissia "Agioi Anargiroi"-2nd Department of Medical Oncology ( Site 07	Nea Kifissia	Attiki
Greece	European Interbalkan Medical Center ( Site 0701)	Thessaloniki
Guatemala	Private Practice- Dr. Rixci Augusto Lenin Ramírez ( Site 0802)	Ciudad de Guatemala
Guatemala	Centro Medico Integral De Cancerología (CEMIC) ( Site 0805)	Quetzaltenango
Guatemala	Centro Regional de Sub Especialidades Médicas SA ( Site 0801)	Quetzaltenango
Israel	Rambam Health Care Campus-Oncology ( Site 1001)	Haifa
Israel	Shaare Zedek Medical Center ( Site 1003)	Jerusalem
Israel	Rabin Medical Center ( Site 1004)	Petah Tikva
Israel	Sheba Medical Center-ONCOLOGY ( Site 1000)	Ramat Gan
Israel	Sourasky Medical Center ( Site 1002)	Tel Aviv
Italy	Azienda Ospedaliera Spedali Civili di Brescia ( Site 1105)	Brescia
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori ( Site 1100)	Milan	Lombardia
Italy	Ospedale San Raffaele ( Site 1104)	Milano	Lombardia
Italy	Ospedale San Gerardo-ASST Monza-Oncologia ( Site 1102)	Monza	Lombardia
Italy	Istituto Nazionale Tumori IRCCS Fondazione Pascale-Oncologia medica Toraco-Polmonare ( Site 1107)	Napoli	Campania
Italy	Fondazione IRCCS Policlinico San Matteo ( Site 1103)	Pavia	Lombardia
Italy	Policlinico Universitario Campus Bio-Medico-Radiation Oncology ( Site 1101)	Roma	Lazio
Japan	Kansai Medical University Hospital ( Site 1207)	Hirakata	Osaka
Japan	Saitama Prefectural Cancer Center ( Site 1201)	Ina-machi	Saitama
Japan	Kobe Minimally Invasive Cancer Center ( Site 1210)	Kobe	Hyogo
Japan	Japanese Foundation for Cancer Research ( Site 1202)	Koto	Tokyo
Japan	Kurume University Hospital ( Site 1212)	Kurume	Fukuoka
Japan	National Hospital Organization Shikoku Cancer Center ( Site 1211)	Matsuyama	Ehime
Japan	Miyagi Cancer Center ( Site 1200)	Natori	Miyagi
Japan	Niigata Cancer Center Hospital ( Site 1205)	Niigata-shi	Niigata
Japan	Osaka International Cancer Institute ( Site 1209)	Osaka
Japan	Sendai Kousei Hospital ( Site 1213)	Sendai	Miyagi
Japan	Showa University Hospital ( Site 1203)	Shinagawa	Tokyo
Japan	Osaka Medical and Pharmaceutical University Hospital ( Site 1208)	Takatsuki	Osaka
Japan	Kanagawa cancer center ( Site 1204)	Yokohama	Kanagawa
Korea, Republic of	Chungbuk National University Hospital-Internal medicine ( Site 2400)	Cheongju-si	Chungbuk
Korea, Republic of	Severance Hospital, Yonsei University Health System-Lung Cancer Center ( Site 2403)	Seoul
Korea, Republic of	Ajou University Hospital-Hematology-Oncology ( Site 2402)	Suwon-si	Kyonggi-do
Korea, Republic of	The Catholic University Of Korea St. Vincent's Hospital-Medical Oncology ( Site 2401)	Suwon-si	Kyonggi-do
Malaysia	Hospital Pulau Pinang ( Site 1400)	George Town	Pulau Pinang
Malaysia	Hospital Kuala Lumpur-Radiotherapy and Oncology ( Site 1401)	Kuala Lumpur
Malaysia	University Malaya Medical Centre-Clinical Oncology ( Site 1402)	Lembah Pantai	Kuala Lumpur
Mexico	Centro Oncologico de Chihuahua-Unidad de Investigacion Clinica ( Site 1507)	Chihuahua
Mexico	Actualidad Basada en la Investigación del Cáncer-Lung Cancer ( Site 1505)	Guadalajara	Jalisco
Mexico	Arké SMO S.A. de C.V. ( Site 1504)	Mexico	Distrito Federal
Mexico	Centro de Investigacion Clinica de Oaxaca ( Site 1501)	Oaxaca
Portugal	Hospital CUF Descobertas ( Site 2006)	Lisbon	Lisboa
Portugal	Centro Hospitalar do Porto - Hospital de Santo António ( Site 2004)	Porto
Portugal	Instituto Português de Oncologia do Porto Francisco Gentil, EPE ( Site 2001)	Porto
Romania	Centrul Medical Medicover Victoria ( Site 2106)	Bucharest	Bucuresti
Romania	Centrul de Oncologie "Sfântul Nectarie" ( Site 2100)	Craiova	Dolj
Romania	Amethyst Radiotherapy Center ( Site 2102)	Flore?ti	Cluj
Romania	Radiology Therapeutic Center ( Site 2108)	Otopeni	Ilfov
Romania	Cabinet Medical Oncomed ( Site 2101)	Timi?oara	Timis
South Africa	Cape Town Oncology Trials ( Site 2306)	Cape Town	Western Cape
South Africa	The Oncology Centre ( Site 2300)	Durban	Kwazulu-Natal
South Africa	CANCERCARE LANGENHOVEN DRIVE ONCOLOGY CENTRE ( Site 2304)	Port Elizabeth	Eastern Cape
South Africa	Wilgers Oncology Centre ( Site 2301)	Pretoria	Gauteng
South Africa	Abraham Oncology ( Site 2303)	Richards Bay	Kwazulu-Natal
Spain	HOSPITAL CLÍNIC DE BARCELONA-ICHMO- Clinic Institut of Haematological and Oncological diseases ( Sit	Barcelona	Cataluna
Spain	Hospital Universitari Vall d'Hebron ( Site 2501)	Barcelona
Spain	HOSPITAL UNIVERSITARIO QUIRONSALUD MADRID-ONCOLOGIA MEDICA ( Site 2504)	Pozuelo de Alarcon	Madrid, Comunidad De
Spain	CHUS - Hospital Clinico Universitario-Servicio de Oncologia ( Site 2502)	Santiago de Compostela	La Coruna
Turkey	Baskent University Dr. Turgut Noyan Research and Training Center-ONCOLOGY ( Site 2607)	Adana
Turkey	Ankara City Hospital-Medical Oncology ( Site 2601)	Ankara
Turkey	Ankara Gülhane Eitim ve Aratrma Hastanesi-Oncology ( Site 2602)	Ankara
Turkey	Hacettepe Universitesi-oncology hospital ( Site 2605)	Ankara
Turkey	Memorial Ankara Hastanesi-Medical Oncology ( Site 2609)	Ankara
Turkey	Ege University Medicine of Faculty-Chest Diseases Department ( Site 2603)	Bornova	Izmir
Turkey	TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 2610)	Istanbul
Turkey	I.E.U. Medical Point Hastanesi-Oncology ( Site 2612)	Izmir, Karsiyaka	Izmir
Turkey	Medipol Mega Universite Hastanesi-oncology ( Site 2611)	Stanbul	Istanbul
United States	MFSMC-HJWCI ( Site 2804)	Baltimore	Maryland
United States	Boston Medical Center ( Site 2829)	Boston	Massachusetts
United States	University of Chicago Medical Center ( Site 2828)	Chicago	Illinois
United States	Millennium Oncology Research Clinic ( Site 2801)	Hollywood	Florida
United States	Millennium Research & Clinical Development ( Site 2811)	Houston	Texas
United States	Franciscan St. Francis Health ( Site 2812)	Indianapolis	Indiana
United States	Lancaster General Hospital - Ann B Barshinger Cancer Institute ( Site 2827)	Lancaster	Pennsylvania
United States	VA Long Beach Healthcare System ( Site 2831)	Long Beach	California
United States	VA West Los Angeles Medical Center ( Site 2808)	Los Angeles	California
United States	Rutgers Cancer Institute of New Jersey ( Site 2805)	New Brunswick	New Jersey
United States	Icahn School of Medicine at Mount Sinai ( Site 2821)	New York	New York
United States	Mid Florida Hematology and Oncology Center ( Site 2800)	Orange City	Florida
United States	Thomas Jefferson University - Clinical Research Institute ( Site 2813)	Philadelphia	Pennsylvania
United States	Kaiser Permanente Northwest-Central Interstate--Oncology ( Site 2816)	Portland	Oregon
United States	Cox Medical Center North-Cox Medical Center/Hulston Cancer Center/ Radiation Oncology ( Site 2837)	Springfield	Missouri
United States	MultiCare Health System ( Site 2817)	Tacoma	Washington
United States	Central Texas Veterans health care-Oncology & Hematology ( Site 2819)	Temple	Texas
United States	White Plains Hospital ( Site 2835)	White Plains	New York
United States	University of Massachusetts Chan Medical School ( Site 2815)	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Chile,  China,  Costa Rica,  Dominican Republic,  Germany,  Greece,  Guatemala,  Israel,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Mexico,  Portugal,  Romania,  South Africa,  Spain,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS) For All Participants	PFS is defined as the time from randomization to the first documented disease progression (PD) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) or death due to any cause, whichever occurs first. 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 =5 mm. Note: The appearance of one or more lesions and the unequivocal progression of non-target lesions is also considered PD. PFS per RECIST 1.1 will be assessed by blinded independent central review (BICR).	Up to approximately 55 months
Primary	Progression-Free Survival (PFS) For Participants With Programmed Cell Death Ligand 1 (PD-L1) Tumor Proportion Score (TPS) =1%	PFS is defined as the time from randomization to the first documented disease progression (PD) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) or death due to any cause, whichever occurs first. 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 =5 mm. Note: The appearance of one or more lesions and the unequivocal progression of non-target lesions is also considered PD. PFS per RECIST 1.1 will be assessed by blinded independent central review (BICR).	Up to approximately 55 months
Primary	Overall Survival (OS) For All Participants	OS is defined as the time from randomization to death due to any cause.	Up to approximately 75 months
Primary	Overall Survival (OS) For Participants With Programmed Cell Death Ligand 1 (PD-L1) Tumor Proportion Score (TPS) =1%	OS is defined as the time from randomization to death due to any cause.	Up to approximately 75 months
Secondary	Objective Response Rate (ORR) For All Participants	ORR is defined as the percentage of participants who have a best response of confirmed 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 Version 1.1 (RECIST 1.1). CR or PR by RECIST 1.1 will be assessed by blinded independent central review (BICR).	Up to approximately 75 months
Secondary	Objective Response Rate (ORR) For Participants With Programmed Cell Death Ligand 1 (PD-L1) Tumor Proportion Score (TPS) =1%	ORR is defined as the percentage of participants who have a best response of confirmed 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 Version 1.1 (RECIST 1.1). CR or PR by RECIST 1.1 will be assessed by blinded independent central review (BICR).	Up to approximately 75 months
Secondary	Number of Participants Who Experience at Least One Adverse Event (AE)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.	Up to approximately 75 months
Secondary	Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.	Up to approximately 75 months
Secondary	Duration of Response (DOR) For All Participants	Duration of Response (DOR) is the time from first documented evidence of 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 Version 1.1 (RECIST 1.1) until progressive disease (PD) or death. DOR per RECIST 1.1 will be assessed by blinded independent central review (BICR).	Up to approximately 75 months
Secondary	Duration of Response (DOR) For Participants With Programmed Cell Death Ligand 1 (PD-L1) Tumor Proportion Score (TPS) =1%	Duration of Response (DOR) is the time from first documented evidence of 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 Version 1.1 (RECIST 1.1) until progressive disease (PD) or death. DOR per RECIST 1.1 will be assessed by blinded independent central review (BICR).	Up to approximately 75 months
Secondary	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) For All Participants	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). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status.	Baseline (at randomization) and at the end of study (approximately 75 months post randomization)
Secondary	Change from Baseline in the Global Health Status/Quality of Life Items 29 and 30 Combined Score on the EORTC QLQ-C30 For Participants With PD-L1 TPS =1%	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). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status.	Baseline (at randomization) and at the end of study (approximately 75 months post randomization)
Secondary	Change from Baseline in Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ-C30 For All Participants	The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life (QoL) of individuals with cancer. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100, with a higher score indicating a better quality of life.	Baseline (at randomization) and at the end of study (approximately 75 months post randomization)
Secondary	Change from Baseline in Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ-C30 For Participants With PD-L1 TPS =1%	The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life (QoL) of individuals with cancer. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100, with a higher score indicating a better quality of life.	Baseline (at randomization) and at the end of study (approximately 75 months post randomization)
Secondary	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) For All Participants	The EORTC QLQ-LC13 is a lung cancer specific health-related quality of life (QoL) questionnaire. Participant responses to the question "Have you coughed?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates more frequent coughing.	Baseline (at randomization) and at the end of study (approximately 75 months post randomization)
Secondary	Change from Baseline in Cough Score (Item 31) on the EORTC QLQ-LC13 For Participants With PD-L1 TPS =1%	The EORTC QLQ-LC13 is a lung cancer specific health-related quality of life (QoL) questionnaire. Participant responses to the question "Have you coughed?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates more frequent coughing.	Baseline (at randomization) and at the end of study (approximately 75 months post randomization)
Secondary	Change from Baseline in Chest Pain Score (Item 40) on the EORTC QLQ-LC13 For All Participants	The EORTC QLQ-LC13 is a lung cancer specific health-related quality of life (QoL) questionnaire. Participant responses to the question "Have you had pain in your chest?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates more chest pain.	Baseline (at randomization) and at the end of study (approximately 75 months post randomization)
Secondary	Change from Baseline in Chest Pain Score (Item 40) on the EORTC QLQ-LC13 For Participants With PD-L1 TPS =1%	The EORTC QLQ-LC13 is a lung cancer specific health-related quality of life (QoL) questionnaire. Participant responses to the question "Have you had pain in your chest?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates more chest pain.	Baseline (at randomization) and at the end of study (approximately 75 months post randomization)
Secondary	Change from Baseline in Dyspnea (Item 8) Score on the EORTC QLQ-C30 For All Participants	The EORTC QLQ-C30 is a cancer specific health-related quality of life (QoL) questionnaire. Participant responses to the question "Were you short of breath?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a worse level of dyspnea.	Baseline (at randomization) and at the end of study (approximately 75 months post randomization)
Secondary	Change from Baseline in Dyspnea (Item 8) Score on the EORTC QLQ-C30 For Participants With PD-L1 TPS =1%	The EORTC QLQ-C30 is a cancer specific health-related quality of life (QoL) questionnaire. Participant responses to the question "Were you short of breath?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a worse level of dyspnea.	Baseline (at randomization) and at the end of study (approximately 75 months post randomization)
Secondary	Time to True Deterioration (TTD) in the Global Health Status/Quality of Life Items 29 and 30 Combined Score on the EORTC QLQ-C30 For All Participants	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). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall outcome. TTD is defined as the time to first onset of =10-point deterioration (out of 100) from baseline and confirmed by a second adjacent =10-point deterioration from baseline.	Up to approximately 75 months post randomization
Secondary	Time to True Deterioration (TTD) in the Global Health Status/Quality of Life Items 29 and 30 Combined Score on the EORTC QLQ-C30 For Participants With PD-L1 TPS =1%	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). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall outcome. TTD is defined as the time to first onset of =10-point deterioration (out of 100) from baseline and confirmed by a second adjacent =10-point deterioration from baseline.	Up to approximately 75 months post randomization
Secondary	Time to True Deterioration (TTD) in Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ-C30 For All Participants	The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life (QoL) of individuals with cancer. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better level of function. TTD is defined as the time to first onset of =10-point deterioration (out of 100) from baseline and confirmed by a second adjacent =10-point deterioration from baseline.	Up to approximately 75 months post randomization
Secondary	Time to True Deterioration (TTD) in Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ-C30 For Participants With PD-L1 TPS =1%	The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life (QoL) of individuals with cancer. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better level of function. TTD is defined as the time to first onset of =10-point deterioration (out of 100) from baseline and confirmed by a second adjacent =10-point deterioration from baseline.	Up to approximately 75 months post randomization
Secondary	Time to True Deterioration (TTD) in Cough Score (Item 31) on the EORTC QLQ-LC13 For All Participants	The EORTC QLQ-LC13 is a lung cancer specific health-related quality of life (QoL) questionnaire. Participant responses to the question "Have you coughed?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates more frequent coughing. TTD is defined as the time to first onset of =10-point deterioration (out of 100) from baseline and confirmed by a second adjacent =10-point deterioration from baseline.	Up to approximately 75 months post randomization
Secondary	Time to True Deterioration (TTD) in Cough Score (Item 31) on the EORTC QLQ-LC13 For Participants With PD-L1 TPS =1%	The EORTC QLQ-LC13 is a lung cancer specific health-related quality of life (QoL) questionnaire. Participant responses to the question "Have you coughed?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates more frequent coughing. TTD is defined as the time to first onset of =10-point deterioration (out of 100) from baseline and confirmed by a second adjacent =10-point deterioration from baseline.	Up to approximately 75 months post randomization
Secondary	Time to True Deterioration (TTD) in Chest Pain Score (Item 40) on the EORTC QLQ-LC13 For All Participants	The EORTC QLQ-LC13 is a lung cancer specific health-related quality of life (QoL) questionnaire. Participant responses to the question "Have you had pain in your chest?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates more chest pain. TTD is defined as the time to first onset of =10-point deterioration (out of 100) from baseline and confirmed by a second adjacent =10-point deterioration from baseline.	Up to approximately 75 months post randomization
Secondary	Time to True Deterioration (TTD) in Chest Pain Score (Item 40) on the EORTC QLQ-LC13 For Participants With PD-L1 TPS =1%	The EORTC QLQ-LC13 is a lung cancer specific health-related quality of life (QoL) questionnaire. Participant responses to the question "Have you had pain in your chest?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates more chest pain. TTD is defined as the time to first onset of =10-point deterioration (out of 100) from baseline and confirmed by a second adjacent =10-point deterioration from baseline.	Up to approximately 75 months post randomization
Secondary	Time to True Deterioration (TTD) in Dyspnea (Item 8) Score on the EORTC QLQ-C30 For All Participants	The EORTC QLQ-C30 is a cancer specific health-related quality of life (QoL) questionnaire. Participant responses to the question "Were you short of breath?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a worse level of dyspnea. TTD is defined as the time to first onset of =10-point deterioration (out of 100) from baseline and confirmed by a second adjacent =10-point deterioration from baseline.	Up to approximately 75 months post randomization
Secondary	Time to True Deterioration (TTD) in Dyspnea (Item 8) Score on the EORTC QLQ-C30 For Participants With PD-L1 TPS =1%	The EORTC QLQ-C30 is a cancer specific health-related quality of life (QoL) questionnaire. Participant responses to the question "Were you short of breath?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a worse level of dyspnea. TTD is defined as the time to first onset of =10-point deterioration (out of 100) from baseline and confirmed by a second adjacent =10-point deterioration from baseline.	Up to approximately 75 months post randomization

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary