Study of Pembrolizumab With Concurrent Chemoradiation Therapy Followed by Pembrolizumab With or Without Olaparib in Stage III Non-Small Cell Lung Cancer (NSCLC) (MK-7339-012/KEYLYNK-012)

Carcinoma, Non-Small-Cell Lung Clinical Trial

Official title:

A Phase 3 Study of Pembrolizumab (MK-3475) in Combination With Concurrent Chemoradiation Therapy Followed by Pembrolizumab With or Without Olaparib vs Concurrent Chemoradiation Therapy Followed by Durvalumab in Participants With Unresectable, Locally Advanced, Stage III Non-Small Cell Lung Cancer (NSCLC)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04380636
• Other study ID #: 7339-012
• Secondary ID: MK-7339-012KEYLY
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: July 6, 2020
• Est. completion date: February 15, 2027

Study information

• Verified date: April 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the efficacy and safety of pembrolizumab in combination with concurrent chemoradiation therapy followed by either pembrolizumab with olaparib placebo (Arm 1) or with olaparib (Arm 2) compared to concurrent chemoradiation therapy followed by durvalumab (Arm 3) in participants with unresectable, locally advanced NSCLC. Arms 1 and 2 will be studied in a double-blind design and Arm 3 will be open-label. The primary hypotheses are:

1. Pembrolizumab with concurrent chemoradiation therapy followed by pembrolizumab with olaparib is superior to concurrent chemoradiation therapy followed by durvalumab with respect to progression-free survival (PFS) and overall survival (OS)

2. Pembrolizumab with concurrent chemoradiation therapy followed by pembrolizumab is superior to concurrent chemoradiation therapy followed by durvalumab with respect to PFS and OS

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 870
• Est. completion date: February 15, 2027
• Est. primary completion date: July 6, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 unable to undergo surgery with curative intent for Stage III NSCLC

• Has no evidence of metastatic disease indicating Stage IV NSCLC

• Has measurable disease as defined by RECIST 1.1

• Has not received prior treatment (chemotherapy, targeted therapy or radiotherapy) for Stage III NSCLC; participants who have received neoadjuvant and/or adjuvant therapy for early stage disease are not eligible

• Has provided a 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

• A male participant must agree to use contraception and refrain from donating sperm during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention unless confirmed to be azoospermic (vasectomized or secondary to medical cause). The length of time required to continue contraception for each study intervention is as follows: Olaparib, platinum doublet, and radiotherapy: 90 days

• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and agrees to use contraception and refrain from donating eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during the treatment period and for at least the time needed to eliminate each study intervention after the last dose of study intervention and agrees to abstain from breastfeeding during the study intervention period and for at least 120 days after the last dose of study intervention. The length of time required to continue contraception for each study intervention is as follows: Pembrolizumab: 120 days; Olaparib, platinum doublet, and radiotherapy: 180 days

• Has a negative highly sensitive pregnancy test ([urine or serum] as required by local regulations) within 24 hours for urine or within 72 hours for serum before the first dose of study intervention. If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.

• Has had her medical history, menstrual history, and recent sexual activity reviewed by the investigator to decrease the risk for inclusion of a woman with an early undetected pregnancy.

• Has adequate pulmonary function tests

• Has adequate organ function

• Has provided written informed consent

Exclusion Criteria:

• Has small cell lung cancer or a mixed tumor with presence of small cell elements

• Has myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or has features suggestive of MDS/AML

• Has had documented weight loss >10% (from baseline) in the preceding 3 months

• Has received prior radiotherapy to the thorax, including radiotherapy to the esophagus, mediastinum, or for breast cancer

• Has received prior therapy with an anti-programmed cell death 1 (ant-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), or anti- programmed cell death ligand 2 (anti-PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor

• Has received prior therapy with olaparib or with any other polyadenosine 5'diphosphoribose (polyADP ribose) polymerization (PARP) inhibitor

• Has had major surgery <4 weeks prior to the first dose of study treatment (except for placement of vascular access)

• Is expected to require any other form of antineoplastic therapy, while on study

• Has received a live or live attenuated vaccine within 30 days before the first dose of study intervention; administration of killed vaccines is allowed

• Has received colony-stimulating factors (e.g., granulocyte colony-stimulating factor [GCSF], granulocyte-macrophage colony-stimulating factor [GM-CSF] or recombinant erythropoietin) within 28 days prior to the first dose of study treatment

• Is currently receiving either strong (phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate (e.g. bosentan, efavirenz, modafinil) inducers of CYP3A4 that cannot be discontinued for the duration of the study

• Is currently receiving either strong (eg, itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil) inhibitors of cytochrome P450 (CYP)3A4 that cannot be discontinued for the duration of the study

• 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 before, during, and for at least 2 days after administration of pemetrexed

• Is unable/unwilling to take folic acid, vitamin B12, and dexamethasone during administration of pemetrexed

• Has received an investigational agent or has used an investigational device within 4 weeks prior to study treatment

• The presence of uncontrolled, potentially reversible cardiac conditions, as judged by the investigator or has congenital long QT syndrome

• 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 intervention

• Has a known additional malignancy that is progressing or has required active treatment within the past 5 years with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ (excluding carcinoma-in situ-of the bladder) that have undergone potentially curative therapy

• Has severe hypersensitivity (=Grade 3) to 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 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 active tuberculosis (TB; Mycobacterium tuberculosis) and is receiving treatment

• Has a history or current evidence of any condition, therapy, laboratory abnormality or other circumstance that might confound the results of the study, or interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator

• Is considered a poor medical risk due to a serious, uncontrolled medical disorder or nonmalignant systemic disease in the opinion of the treating investigator

• Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study

• Is unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption

• Has had an allogenic tissue/solid organ transplant

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms

Intervention

Biological:
• Pembrolizumab
intravenous (IV) infusion

Drug:
• Olaparib
oral tablets
• Placebo for olaparib
oral tablets
• Etoposide
IV infusion
• Carboplatin
IV infusion
• Cisplatin
IV infusion
• Paclitaxel
IV infusion
• Pemetrexed
IV infusion

Radiation:
• Thoracic Radiotherapy
external beam radiation

Drug:
• Durvalumab
IV infusion

Locations

Country	Name	City	State
Argentina	Clinica Adventista Belgrano-Oncology ( Site 4002)	Caba
Argentina	Instituto Médico Río Cuarto ( Site 4003)	Río Cuarto	Cordoba
Canada	Queen Elizabeth II Health Sciences Centre ( Site 0100)	Halifax	Nova Scotia
Canada	Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0102)	Montreal	Quebec
Canada	CIUSSS Ouest de l Ile - St-Mary s Hospital ( Site 0108)	Montreal	Quebec
Canada	McGill University Health Center - Research Institute ( Site 0114)	Montreal	Quebec
Canada	Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0	Quebec
Chile	Bradford Hill Norte ( Site 0204)	Antofagasta
Chile	Bradfordhill ( Site 0200)	Santiago	Region M. De Santiago
Chile	OrlandiOncologia ( Site 0201)	Santiago	Region M. De Santiago
Chile	Centro Investigación del Cáncer James Lind ( Site 0202)	Temuco	Araucania
Chile	Oncocentro ( Site 0203)	Vina del Mar	Valparaiso
China	Beijing Cancer Hospital ( Site 3212)	Beijing	Beijing
China	Beijing Cancer Hospital ( Site 3224)	Beijing	Beijing
China	Cancer Hospital Chinese Academy of Medical Sciences ( Site 3213)	Beijing	Beijing
China	Peking Union Medical College Hospital ( Site 3201)	Beijing	Beijing
China	Jilin Cancer Hospital ( Site 3230)	Changchun	Jilin
China	Hunan Cancer Hospital ( Site 3225)	Changsha	Hunan
China	Hunan Cancer Hospital ( Site 3238)	Changsha	Hunan
China	Second Xiangya Hospital of Central-South University ( Site 3227)	Changsha	Hunan
China	Xiangya Hospital of Central South University ( Site 3637)	Changsha	Hunan
China	West China Hospital of Sichuan University ( Site 3202)	Chengdu	Sichuan
China	Daping Hospital,Third Military Medical University ( Site 3235)	Chongqing	Chongqing
China	Fujian Provincial Cancer Hospital ( Site 3226)	Fuzhou	Fujian
China	The 1st Affil Hosp of College of Medicine, Zhejiang Univ ( Site 3232)	Hangzhou	Zhejiang
China	The Second Affiliated Hospital of Nanchang University ( Site 3206)	Nanchang	Jiangxi
China	Jiangsu Cancer Hospital ( Site 3234)	Nanjing	Jiangsu
China	Shanghai Chest Hospital ( Site 3207)	Shangai	Shanghai
China	Shanghai Pulmonary Hospital ( Site 3203)	Shanghai	Shanghai
China	Zhongshan Hospital Fudan University ( Site 3220)	Shanghai	Shanghai
China	Cancer Hospital Chinese Academy Of Medical Sciences. Shenzhen Center ( Site 3200)	Shenzhen	Guangdong
China	Peking University Shenzhen Hospital ( Site 3216)	Shenzhen	Guangdong
China	Tianjin Medical University Cancer Institute & Hospital ( Site 3204)	Tianjin	Tianjin
China	Hubei Cancer Hospital ( Site 3218)	Wuhan	Hubei
China	Wuhan Union Hospital ( Site 3222)	Wuhan	Hubei
China	The First Affiliated Hospital of Xiamen University ( Site 3219)	Xiamen	Fujian
China	Henan Cancer Hospital ( Site 3205)	Zhengzhou	Henan
Czechia	Masarykuv onkologicky ustav ( Site 2206)	Brno	Brno-mesto
Czechia	Krajska nemocnice Liberec, a.s. ( Site 2209)	Liberec
Czechia	Nemocnice Na Plesi s.r.o. ( Site 2202)	Nova Ves pod Plesi	Pribram
Czechia	Fakultni nemocnice Ostrava ( Site 2201)	Ostrava	Ostrava Mesto
Czechia	Fakultni nemocnice Kralovske Vinohrady-Radioterapeuticka a onkologicka klinika ( Site 2200)	PRague	Praha 10
Czechia	Fakultni nemocnice v Motole ( Site 2210)	Praha	Praha, Hlavni Mesto
Czechia	Vseobecna fakultni nemocnice v Praze ( Site 2208)	Praha 2
Czechia	Nemocnice Na Bulovce ( Site 2205)	Praha 8
Estonia	North Estonia Medical Centre Foundation ( Site 1601)	Tallin	Harjumaa
Estonia	Tartu University Hospital ( Site 1600)	Tartu	Tartumaa
France	Clinique de l'Europe-Service de pneumologie ( Site 0816)	Amiens	Somme
France	Hopital Avicenne ( Site 0803)	Bobigny	Seine-Saint-Denis
France	C.H.R.U. de Brest - Hopital Morvan ( Site 0806)	Brest	Bretagne
France	Centre Hospitalier Annecy Genevois ( Site 0811)	Epagny Metz Tessy	Haute-Savoie
France	CHD Vendee ( Site 0807)	La Roche sur Yon	Vendee
France	Clinique Clairval ( Site 0802)	Marseille	Bouches-du-Rhone
France	H.I.A. Sainte-Anne ( Site 0815)	Toulon	Var
France	Clinique Teissier Groupe ( Site 0808)	Valenciennes	Nord
Germany	Zentralklinik Bad Berka GmbH ( Site 0905)	Bad Berka	Thuringen
Germany	Charite-Universitaetsmedizin Berlin Campus Virchow-Klinikum ( Site 0900)	Berlin
Germany	Universitätsmedizin Göttingen - Georg-August-Universität ( Site 0917)	Göttingen	Niedersachsen
Germany	LungenClinic Grosshansdorf GmbH ( Site 0901)	Grosshansdorf	Schleswig-Holstein
Germany	Katholisches Marienkrankenhaus gGmbH ( Site 0902)	Hamburg
Germany	Universitaetsklinikum Jena ( Site 0911)	Jena	Thuringen
Germany	Johannes Wesling Klinikum Minden ( Site 0908)	Minden	Nordrhein-Westfalen
Germany	GEHO Muenster ( Site 0910)	Muenster	Nordrhein-Westfalen
Germany	Johanna Etienne Hospital-Klinik für Onkologie ( Site 0916)	Neuss	Nordrhein-Westfalen
Hungary	Orszagos Koranyi Pulmonologiai Intezet ( Site 2305)	Budapest
Hungary	Országos Korányi Pulmonológiai Intézet-VI. Tüdöbelosztály és Bronchológia ( Site 2309)	Budapest
Hungary	Petz Aladar Megyei Oktato Korhaz ( Site 2306)	Gyor	Gyor-Moson-Sopron
Hungary	Bekes Megyei Kozponti Korhaz - Pandy Kalman Tagkorhaza ( Site 2303)	Gyula	Bekes
Hungary	Bacs-Kiskun Megyei Korhaz-Onkoradiologiai Kozpont ( Site 2302)	Kecskemét	Bacs-Kiskun
Italy	Azienda Ospedaliero Universitaria Careggi ( Site 1001)	Florence	Firenze
Italy	Azienda Ospedaliera Vito Fazzi ( Site 1003)	Lecce
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 1008)	Milano
Italy	Policlinico di Modena ( Site 1007)	Modena
Italy	Policlinico Agostino Gemelli ( Site 1002)	Roma
Italy	Istituto Clinico Humanitas Research Hospital ( Site 1000)	Rozzano	Lombardia
Italy	Azienda Ospedaliera Umberto I- Torrette ( Site 1009)	Torrette	Ancona
Italy	A.O.U. Santa Maria della Misericordia di Udine ( Site 1004)	Udine
Japan	National Hospital Organization Kyushu Cancer Center ( Site 3104)	Fukuoka
Japan	Kansai Medical University Hospital ( Site 3103)	Hirakata	Osaka
Japan	Kobe Minimally Invasive Cancer Center ( Site 3100)	Kobe	Hyogo
Japan	Kurume University Hospital ( Site 3112)	Kurume	Fukuoka
Japan	Niigata Cancer Center Hospital ( Site 3109)	Niigata
Japan	Osaka International Cancer Institute ( Site 3106)	Osaka
Japan	Osaka Medical and Pharmaceutical University Hospital ( Site 3110)	Takatsuki	Osaka
Japan	Juntendo University Hospital ( Site 3111)	Tokyo
Japan	Showa University Hospital ( Site 3105)	Tokyo
Japan	The Cancer Institute Hospital of JFCR ( Site 3107)	Tokyo
Japan	Tokyo Metropolitan Komagome Hospital ( Site 3108)	Tokyo
Japan	Kanagawa Cancer Center ( Site 3101)	Yokohama	Kanagawa
Korea, Republic of	Chungbuk National University Hospital ( Site 2802)	Cheongju-si	Chungbuk
Korea, Republic of	Keimyung University Dongsan Hospital ( Site 2807)	Daegu	Taegu-Kwangyokshi
Korea, Republic of	National Cancer Center ( Site 2800)	Goyang-si	Kyonggi-do
Korea, Republic of	The Catholic University of Korea St. Vincent s Hospital ( Site 2805)	Gyeonggi-do	Kyonggi-do
Korea, Republic of	Gyeongsang National University Hospital ( Site 2804)	Jinju-si	Kyongsangnam-do
Korea, Republic of	Seoul National University Bundang Hospital ( Site 2801)	Seongnam-si	Kyonggi-do
Korea, Republic of	Kangbuk Samsung Hospital ( Site 2806)	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System ( Site 2808)	Seoul
Korea, Republic of	Ajou University Hospital ( Site 2803)	Suwon-si	Kyonggi-do
Latvia	Pauls Stradins Clinical University Hospital ( Site 1501)	Riga
Latvia	Riga East Clinical University Hospital ( Site 1500)	Riga
Lithuania	Hospital of Lithuanian University of Health Sciences Kauno klinikos-Pulmonology ( Site 4201)	Kaunas	Kauno Apskritis
Lithuania	National Cancer Institute-Department of Thoracic Surgery and Oncology ( Site 4200)	Vilnius	Vilniaus Miestas
Mexico	Hospital Civil de Guadalajara Fray Antonio Alcalde ( Site 0500)	Guadalajara	Jalisco
Mexico	Hospital Universitario "Dr. Jose Eleuterio Gonzalez" ( Site 0508)	Monterrey	Nuevo Leon
Mexico	CLIMERS Clinical Medical Research ( Site 0506)	Orizaba	Veracruz
Mexico	Instituto Nacional de Cancerologia ( Site 0502)	Tlalpan
Norway	Vestre Viken HF Drammen Sykehus ( Site 1101)	Drammen	Buskerud
Norway	Sykehuset Oestfold ( Site 1107)	Gralum	Ostfold
Norway	Akershus Universitetssykehus HF ( Site 1106)	Lorenskog	Akershus
Norway	Oslo Universitetssykehus HF. Ulleval ( Site 1100)	Oslo
Norway	Helse Stavanger HF Stavanger Universitetssjukehus ( Site 1103)	Stavanger	Rogaland
Peru	Hospital Nacional Carlos Alberto Seguin Escobedo ESSALUD ( Site 0604)	Arequipa	Ariqipa
Peru	Clinica San Gabriel ( Site 0601)	Lima
Peru	Hospital Nacional Cayetano Heredia ( Site 0602)	Lima
Peru	IPOR Instituto Peruano de Oncología & Radioterapia ( Site 0606)	Lima
Peru	Oncosalud ( Site 0605)	Lima	Muni Metro De Lima
Peru	Detecta Clínica ( Site 0607)	Surquillo	Muni Metro De Lima
Poland	Szpital Morski im. PCK. Szpitale Pomorskie Sp. Z o.o ( Site 2400)	Gdynia	Pomorskie
Poland	SPZOZ MSWIA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie ( Site 2401)	Olsztyn	Warminsko-mazurskie
Poland	Mazowiecki Szpital Wojewódzki w Siedlcach-Siedleckie Centrum Onkologii ( Site 2404)	Siedlce	Mazowieckie
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie (	Warszawa	Mazowieckie
Romania	Spitalul Universitar de Urgenta Bucuresti ( Site 2508)	Bucharest	Bucuresti
Romania	Gral Medical SRL-Medical Oncology ( Site 2511)	Bucure?ti	Bucuresti
Romania	S.C.Focus Lab Plus S.R.L ( Site 2500)	Bucuresti
Romania	Institutul Oncologic Prof.Dr. Ion Chiricuta Cluj-Napoca ( Site 2506)	Cluj Napoca	Cluj
Romania	S.C. Radiotherapy Center Cluj S.R.L ( Site 2503)	Comuna Floresti	Cluj
Romania	Spitalul Clinic Judetean De Urgenta Constanta ( Site 2501)	Constanta
Romania	Centrul de Oncologie "Sfântul Nectarie"-Medical Oncology ( Site 2510)	Craiova	Dolj
Romania	Institutul Regional de Oncologie Iasi ( Site 2505)	Iasi
Romania	Radiology Therapeutic Center-Oncology ( Site 2502)	Otopeni	Ilfov
Romania	S C Oncocenter Oncologie Clinica S R L-Medical Oncology ( Site 2509)	Timi?oara	Timis
Romania	Policlinica Oncomed SRL ( Site 2504)	Timisoara	Timis
Russian Federation	Chelyabinsk Regional Clinical Oncological Dispensary ( Site 1913)	Chelyabinsk	Chelyabinskaya Oblast
Russian Federation	Sverdlovsk Regional Oncology Hospital ( Site 1909)	Ekaterinburg	Sverdlovskaya Oblast
Russian Federation	Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 1911)	Kazan	Tatarstan, Respublika
Russian Federation	MSROI named after P.A. Hertsen branch of FSBI NMRC Radiology ( Site 1903)	Moscow	Moskva
Russian Federation	Nizhniy Novgorod Region Oncology Dispensary ( Site 1914)	Nizhniy Novgorod	Nizhegorodskaya Oblast
Russian Federation	Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 1905)	Saint-Petersburg	Sankt-Peterburg
Russian Federation	Medical institute named after Berezin Sergey ( Site 1906)	St. Petersburg	Sankt-Peterburg
Russian Federation	Yaroslavl Regional SBIH Clinical Oncology Hospital ( Site 1910)	Yaroslavl	Yaroslavskaya Oblast
Spain	H.U. Vall de Hebron ( Site 1201)	Barcelona
Spain	Hospital Clinic de Barcelona ( Site 1204)	Barcelona
Spain	Hospital Universitario Puerta de Hierro (Majadahonda) ( Site 1202)	Majadahonda	Madrid
Spain	H.R.U Málaga - Hospital General ( Site 1206)	Málaga	Malaga
Spain	Hospital Universitario Quiron Madrid ( Site 1200)	Pozuelo de Alarcon	Madrid
Spain	Hospital Universitario Virgen Macarena ( Site 1205)	Sevilla
Spain	Hospital Universitario La Fe ( Site 1203)	Valencia
Thailand	Chulalongkorn University ( Site 3003)	Bangkok	Krung Thep Maha Nakhon
Thailand	Ramathibodi Hospital. ( Site 3000)	Bangkok	Krung Thep Maha Nakhon
Thailand	Chiang Mai University Maharaj Nakorn Chiang Mai Hospital ( Site 3001)	Chiang Mai
Thailand	Srinagarind Hospital. Khon Kaen University ( Site 3002)	Khon Kaen
Turkey	Ankara Bilkent Sehir Hastanesi ( Site 2002)	Ankara	Adana
Turkey	Memorial Ankara Hastanesi ( Site 2006)	Ankara
Turkey	Göztepe Prof. Dr. Süleyman Yalçin Sehir Hastanesi-oncology ( Site 2001)	Istanbul
Turkey	Istanbul Uni. Cerrahpasa Tip Fakultesi ( Site 2000)	Istanbul
Turkey	Medipol Universite Hastanesi ( Site 2003)	Istanbul
Turkey	Ege University Medical Faculty ( Site 2005)	Izmir
Ukraine	Communal nonprofit enterprise "Kherson Regional Oncology Dispensary" of Kherson Regional Council (	Antonivka Village	Khersonska Oblast
Ukraine	Medical center Medikal Plaza of Ecodnipro LLC ( Site 2107)	Dnipro	Dnipropetrovska Oblast
Ukraine	Medical Center of Yuriy Spizhenko LLC.-Clinical Trial ( Site 2104)	Kapitanivka Village	Kyivska Oblast
Ukraine	SOGrigoriev Inst for Med Radiolgy and Oncology of NAMS of Ukraine-Clinical oncology and hematology (	Kharkiv	Kharkivska Oblast
Ukraine	LLC Ukrainian Center of Tomotherapy ( Site 2105)	Kropyvnytskyi	Kirovohradska Oblast
Ukraine	Kyiv City Clinical Oncology Center ( Site 2100)	Kyiv
Ukraine	Medical Center Verum ( Site 2106)	Kyiv	Kyivska Oblast
Ukraine	SNPE National Cancer Institute ( Site 2101)	Kyiv	Kyivska Oblast
United Kingdom	Leeds Teaching Hospitals NHS Trust ( Site 1401)	Leeds
United Kingdom	Guys and St Thomas NHS Foundation Trust ( Site 1410)	London	London, City Of
United Kingdom	Royal Marsden Hospital (Sutton) ( Site 1407)	London	Surrey
United Kingdom	University College Hospital NHS Foundation Trust ( Site 1403)	London-Camden	London, City Of
United Kingdom	Christie NHS Foundation Trust ( Site 1409)	Manchester
United Kingdom	Weston Park Hospital ( Site 1406)	Sheffield	Derbyshire
United Kingdom	Southampton General Hospital ( Site 1400)	Southampton	Worcestershire
United States	Massachusetts General Hospital ( Site 0038)	Boston	Massachusetts
United States	Montefiore Einstein Center ( Site 0083)	Bronx	New York
United States	Novant Health Presbyterian ( Site 0081)	Charlotte	North Carolina
United States	The Lindner Center for Research and Education at The Christ Hospital ( Site 0060)	Cincinnati	Ohio
United States	Henry Ford Hospital ( Site 0045)	Detroit	Michigan
United States	Duke University Medical Center ( Site 0050)	Durham	North Carolina
United States	Fort Wayne Medical Oncology and Hematology ( Site 0094)	Fort Wayne	Indiana
United States	Parkview Research Center ( Site 0032)	Fort Wayne	Indiana
United States	St Joseph Heritage Healthcare-Oncology ( Site 0088)	Fullerton	California
United States	CHI Health St. Francis ( Site 0053)	Grand Island	Nebraska
United States	Memorial Regional Hospital-Memorial Cancer Institute ( Site 0095)	Hollywood	Florida
United States	St. Bernards Medical Center ( Site 0089)	Jonesboro	Arkansas
United States	Franciscan Health Lafayette East ( Site 0031)	Lafayette	Indiana
United States	University of Kentucky ( Site 0096)	Lexington	Kentucky
United States	Long Beach Memorial Medical Center ( Site 0006)	Long Beach	California
United States	UCLA Hematology/Oncology - Santa Monica ( Site 0013)	Los Angeles	California
United States	Norton Brownsboro Hospital-Norton Cancer Institute - Brownsboro ( Site 0035)	Louisville	Kentucky
United States	Miami VA Healthcare System ( Site 0024)	Miami	Florida
United States	University of South Alabama, Mitchell Cancer Institute ( Site 0003)	Mobile	Alabama
United States	Rutgers Cancer Institute of New Jersey ( Site 0054)	New Brunswick	New Jersey
United States	Mid Florida Hematology and Oncology Center ( Site 0022)	Orange City	Florida
United States	Orlando Health, UF Health Cancer Center Inc ( Site 0092)	Orlando	Florida
United States	The Valley Hospital ( Site 0056)	Paramus	New Jersey
United States	Fox Chase Cancer Center ( Site 0063)	Philadelphia	Pennsylvania
United States	Pikeville Medical Center ( Site 0036)	Pikeville	Kentucky
United States	VA St. Louis Health Care System ( Site 0047)	Saint Louis	Missouri
United States	Washington University Siteman Cancer Center ( Site 0046)	Saint Louis	Missouri
United States	St. Joseph Heritage Healthcare Local Lab ( Site 0011)	Santa Rosa	California
United States	Veterans Affairs Puget Sound Health Care System [Seattle, WA] ( Site 0075)	Seattle	Washington
United States	Sanford Cancer Center Oncology Clinic ( Site 0066)	Sioux Falls	South Dakota
United States	Cancer Care Northwest ( Site 0074)	Spokane Valley	Washington
United States	Torrance Memorial Physician Network / Cancer Center ( Site 0093)	Torrance	California
United States	Piedmont Hematology-Oncology Associates ( Site 0080)	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Argentina,  Canada,  Chile,  China,  Czechia,  Estonia,  France,  Germany,  Hungary,  Italy,  Japan,  Korea, Republic of,  Latvia,  Lithuania,  Mexico,  Norway,  Peru,  Poland,  Romania,  Russian Federation,  Spain,  Thailand,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)	PFS is defined as the time from randomization to the first documented disease progression or death due to any cause, whichever occurs first.	Up to approximately 48 months
Primary	Overall Survival (OS)	OS is the time from randomization to death due to any cause.	Up to approximately 72 months
Secondary	Incidence of Adverse Events (AE)	An AE is defined as 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.	Up to approximately 72 months
Secondary	Discontinuation Rate of Study Intervention Due to an Adverse Event (AE)	An AE is defined as as 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.	Up to approximately 72 months
Secondary	Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)	ORR is defined as the percentage of participants who have achieved a Complete Response (CR) or a Partial Response (PR).	Up to approximately 72 months
Secondary	Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)	DOR is defined as the time from first documented evidence of Complete Response (CR) or a Partial Response (PR) until disease progression or death due to any cause, whichever occurs first.	Up to approximately 72 months
Secondary	Change from Baseline in EORTC Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Scale Score	The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions "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). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. The change from baseline in EORTC QLQ-C30 Items 29 and 30 scale scores will be presented.	Baseline (at randomization) and at the end of study (approximately 72 months post randomization)
Secondary	Change From Baseline in Cough Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer Module 13 (EORTC QLQ-LC13) Item 1 Score	The EORTC QLQ-LC13 is a supplemental lung cancer-specific questionnaire that includes a single-item scale score for cough (Item 1). For this item, individual responses to the question "How much did you cough?" are given on a 4-point scale (1=Not at all; 4=Very much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100, with a lower score indicating a better outcome. The change from baseline in the EORTC QLQ-LC13 cough scale score will be presented.	Baseline (at randomization) and at the end of study (approximately 72 months post randomization)
Secondary	Change From Baseline in Chest Pain Using the EORTC QLQ-LC13 Item 10 Score	The EORTC QLQ-LC13 is a supplemental lung cancer-specific questionnaire that includes a single-item scale score for chest pain (Item 10). For this item, individual responses to the question "Have you had pain in your chest?" are given on a 4-point scale (1=Not at all; 4=Very much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100, with a lower score indicating a better outcome. The change from baseline in the EORTC QLQ-LC13 chest pain scale score will be presented.	Baseline (at randomization) and at the end of study (approximately 72 months post randomization)
Secondary	Change From Baseline in Dyspnea Using the EORTC QLQ-C30 Item 8 Score	The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients and includes a single-item scale score for dyspnea (Item 8). 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, with a lower score indicating a better outcome. The change from baseline in the EORTC QLQ-C30 dyspnea scale score will be presented.	Baseline (at randomization) and at the end of study (approximately 72 months post randomization)
Secondary	Change From Baseline in Physical Functioning Using the EORTC QLQ-C30 Items 1- 5 Score	The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. The physical functioning scale consists of participant responses to 5 questions regarding performance of daily activities [1) strenuous activities; 2) long walks; 3) short walks; 4) bed/chair rest; and 5) needing help with eating, dressing, washing themselves or using the toilet]. Participant responses 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. The change from baseline in the EORTC QLQ-C30 physical functioning scale score will be presented.	Baseline (at randomization) and at the end of study (approximately 72 months post randomization)
Secondary	Change from Baseline in Role Functioning Using the EORTC QLQ-C30 Items 6-7 Score	The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. The role functioning scale consists of participant responses to 2 questions regarding limitations in doing work or other activities and pursuing hobbies or leisure activities. Participant responses 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. The change from baseline in the EORTC QLQ-C30 role functioning scale score will be presented.	Baseline (at randomization) and at the end of study (approximately 72 months post randomization)
Secondary	Time to Deterioration (TTD) in HRQoL Using the EORTC QLQ-C30 Items 29 and 30 Score	TTD is defined as the time to first onset of a =10-point decrease from baseline for EORTC QLQ-C30 Items 29 and 30 scale scores. The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions "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). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status.	Up to approximately 72 months post randomization
Secondary	TTD in Cough Using the EORTC QLQ-LC13 Item 1 Score	TTD is defined as the time to first onset of a =10-point decrease from baseline for EORTC QLQ-LC13 Item 1 scale score. The EORTC QLQ-LC13 is a supplemental lung cancer-specific questionnaire that includes a single-item scale score for cough (Item 1). For this item, individual responses to the question "How much did you cough?" are given on a 4-point scale (1=Not at all; 4=Very much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100, with a lower score indicating a better outcome.	Up to approximately 72 months post randomization
Secondary	TTD in Chest Pain Using the EORTC QLQ-LC13 Item 10 Score	TTD is defined as the time to first onset of a =10-point decrease from baseline for EORTC QLQ-LC13 Item 10 scale score. The EORTC QLQ-LC13 is a supplemental lung cancer-specific questionnaire that includes a single-item scale score for chest pain (Item 10). For this item, individual responses to the question "Have you had pain in your chest?" are given on a 4-point scale (1=Not at all; 4=Very much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100, with a lower score indicating a better outcome.	Up to approximately 72 months post randomization
Secondary	TTD in Dyspnea Using the EORTC QLQ-C30 Item 8 Score	TTD is defined as the time to first onset of a =10-point decrease from baseline for EORTC QLQ-C30 Item 8 scale score. The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients and includes a single-item scale score for dyspnea (Item 8). 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, with a lower score indicating a better outcome.	Up to approximately 72 months post randomization
Secondary	TTD in Physical Functioning Using the EORTC QLQ-C30 Items 1- 5 Score	TTD is defined as the time to first onset of a =10-point decrease from baseline for EORTC QLQ-C30 Items 1-5 scale scores. The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. The physical functioning scale consists of participant responses to 5 questions regarding performance of daily activities [1) strenuous activities; 2) long walks; 3) short walks; 4) bed/chair rest; and 5) needing help with eating, dressing, washing themselves or using the toilet]. Participant responses 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.	Up to approximately 72 months post randomization
Secondary	TTD in Role Functioning Using the EORTC QLQ-C30 Items 6-7 Score	TTD is defined as the time to first onset of a =10-point decrease from baseline for EORTC QLQ-C30 Items 6-7 scale scores. The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. The role functioning scale consists of participant responses to 2 questions regarding limitations in doing work or other activities and pursuing hobbies or leisure activities. Participant responses 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.	Up to approximately 72 months post randomization

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary