Efficacy and Safety Study of Pembrolizumab (MK-3475) With or Without Lenvatinib (MK-7902/E7080) in Adults With Programmed Cell Death-Ligand 1 (PD-L1)-Positive Treatment-naïve Nonsmall Cell Lung Cancer (NSCLC) (MK-7902-007/E7080-G000-314/LEAP-007)

Non-small Cell Lung Cancer Clinical Trial

Official title:

A Phase 3, Randomized, Double-blind Trial of Pembrolizumab (MK-3475) With or Without Lenvatinib (E7080/MK-7902) in Participants With Treatment-naïve, Metastatic Nonsmall Cell Lung Cancer (NSCLC) Whose Tumors Have a Tumor Proportion Score (TPS) Greater Than or Equal to 1% (LEAP-007)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03829332
• Other study ID #: 7902-007
• Secondary ID: MK-7902-007E7080
• Status: Completed
• Phase: Phase 3
• Start date: March 13, 2019
• Est. completion date: April 24, 2024

Study information

• Verified date: May 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 safety and efficacy of pembrolizumab (MK-3475) combined with lenvatinib (MK-7902/E7080) compared to pembrolizumab alone (with placebo for lenvatinib) in treatment-naïve adults with no prior systemic therapy for their metastatic non-small cell lung cancer (NSCLC) whose tumors have a programmed cell death-ligand 1 (PD-L1) Tumor Proportion Score (TPS) greater than or equal to 1%.

The primary study hypotheses are that: 1) the combination of pembrolizumab and lenvatinib is superior to pembrolizumab alone as assessed by Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1); and 2) the combination of pembrolizumab and lenvatinib is superior to pembrolizumab alone as assessed by Overall Survival (OS).

Description:

As of 30-Jul-2021, active participants, investigator, and sponsor personnel or delegate(s) involved in the treatment administration or clinical evaluation of the participants will be unblinded. Participants will discontinue lenvatinib and placebo, and participants who remain on treatment will receive open-label pembrolizumab only.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 623
• Est. completion date: April 24, 2024
• Est. primary completion date: May 19, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Has a histologically or cytologically confirmed diagnosis of NSCLC.

• Has Stage IV NSCLC (American Joint Committee on Cancer [AJCC 8th edition]).

• Has measurable disease based on RECIST 1.1.

• Has tumor tissue that demonstrates programmed cell death-ligand 1 (PD-L1) expression in =1% of tumor cells (Tumor Proportion Score [TPS] =1%) as assessed by immunohistochemistry (IHC) 22C3 pharmDx assay (Dako North America, Inc.) at a central laboratory.

• Has a life expectancy of =3 months.

• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days before the first dose of study treatment but before randomization.

• Male participants must agree to the following during the treatment period and for =7 days after the last dose of lenvatinib/matching placebo: 1) Be abstinent from heterosexual intercourse as their preferred and usual lifestyle and agree to remain abstinent, OR 2) Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause).

• Female participants are eligible to participate if not pregnant or breastfeeding, and =1 of the following applies: 1) Is not a woman of child-bearing potential (WOCBP), OR 2) Is a WOCBP and is using a highly effective contraceptive method that has a low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle during the treatment period and for =120 days post pembrolizumab or =30 days post lenvatinib/matching placebo, whichever occurs last.

• Has adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP =150/90 mm Hg and no change in antihypertensive medications within 1 week before randomization.

• Has adequate organ function.

Exclusion Criteria:

• Has known untreated central nervous system metastases and/or carcinomatous meningitis.

• Has active hemoptysis (at least 0.5 teaspoon of bright red blood) within 2 weeks prior to the first dose of study intervention.

• Has radiographic evidence of intratumoral cavitations, encasement, or invasion of a major blood vessel.

• Has a known history of an additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for =3 years since initiation of that therapy. (Note: The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer, or other in situ cancers.)

• Has an active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.

• Has had an allogeneic tissue/solid organ transplant.

• Has a known history of human immunodeficiency virus (HIV) infection.

• Has a history of (noninfectious) pneumonitis that required systemic steroids or current pneumonitis/interstitial lung disease.

• Has a known history of hepatitis B or known active hepatitis C virus infection.

• Has a history of a gastrointestinal condition or procedure that in the opinion of the investigator may affect oral study drug absorption.

• Has significant cardiovascular impairment within 12 months of the first dose of study treatment, such as a history of congestive heart failure greater than New York Heart Association Class II, unstable angina, myocardial infarction, cerebrovascular accident/stroke, or cardiac arrhythmia associated with hemodynamic instability.

• Has not recovered adequately from any toxicity and/or complications from major surgery before starting study treatment.

• Has a known history of active tuberculosis (TB).

• Has an active infection requiring systemic therapy.

• Has previously had a severe hypersensitivity reaction to treatment with a monoclonal antibody or has a known sensitivity or intolerance to any component of lenvatinib or pembrolizumab.

• Has received prior systemic chemotherapy or other targeted or biological antineoplastic therapy for their metastatic NSCLC.

• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], Tumor necrosis factor receptor superfamily, member 4 [OX 40], tumor necrosis factor receptor superfamily member 9 [CD137]) or has received lenvatinib as monotherapy or in combination with anti- programmed cell death protein (anti-PD-1) agents.

• Has received radiotherapy within 14 days before the first dose of study treatment or received lung radiation therapy of >30 Gray (Gy) within 6 months before the first dose of study treatment. (Note: Participants must have recovered from all radiation-related toxicities to =Grade 1, not require corticosteroids, and not have had radiation pneumonitis.)

• Has a diagnosis of immunodeficiency or is receiving any form of immunosuppressive therapy within 7 days before the first dose of study treatment.

• Is receiving systemic steroid therapy (doses >10 mg daily of prednisone equivalent) within 7 days before the first dose of study treatment.

• Has received a live or attenuated vaccine within 30 days before the first dose of study treatment.

• Has had major surgery within 3 weeks prior to first dose of study treatment

• Has pre-existing =Grade 3 gastrointestinal or nongastrointestinal fistula.

Related Conditions & MeSH terms

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

Intervention

Biological:
• Pembrolizumab
IV infusion

Drug:
• Lenvatinib
oral capsule
• Placebo for lenvatinib
oral capsule

Locations

Country	Name	City	State
Australia	The Prince Charles Hospital ( Site 0011)	Chermside	Queensland
Australia	Orange Health Services ( Site 0002)	Orange	New South Wales
Australia	St John of God Murdoch Medical Clinic ( Site 0001)	Perth	Western Australia
Australia	Ballarat Oncology and Haematology Services ( Site 0008)	Wendouree	Victoria
Australia	Wollongong Private Hospital ( Site 0005)	Wollongong	New South Wales
Canada	William Osler Health System (Brampton Civic Hospital) ( Site 0402)	Brampton	Ontario
Canada	Cross Cancer Institute ( Site 0400)	Edmonton	Alberta
Canada	McGill University Health Centre ( Site 0418)	Montreal	Quebec
Canada	Lions Gate Hospital ( Site 0407)	North Vancouver	British Columbia
Canada	Windsor Regional Cancer Program ( Site 0404)	Windsor	Ontario
China	Beijing Cancer Hospital ( Site 0102)	Beijing	Beijing
China	Beijing Chest Hospital Capital Medical University ( Site 0111)	Beijing	Anhui
China	Peking Union Medical College Hospital ( Site 0105)	Beijing	Beijing
China	The First Hospital of Jilin University ( Site 0110)	Chang chun	Jilin
China	Hunan Cancer Hospital ( Site 0104)	Changsha	Hunan
China	Xiangya Hospital of Central South University ( Site 0115)	Changsha	Hunan
China	West China Hospital of Sichuan University ( Site 0117)	Chengdu	Sichuan
China	2nd Affil Hosp of Zhejiang University College of Medicine ( Site 0114)	Hangzhou	Zhejiang
China	Hangzhou First People's Hospital ( Site 0109)	Hangzhou	Zhejiang
China	The First Affiliated Hospital Zhejiang University ( Site 0106)	Hangzhou	Zhejiang
China	Zhejiang Cancer Hospital ( Site 0116)	Hangzhou	Zhejiang
China	Anhui Provincial Hospital ( Site 0108)	Hefei	Anhui
China	The First Affiliated Hospital of Anhui Medical University ( Site 0113)	Hefei	Anhui
China	Jiangsu Cancer Hospital ( Site 0101)	Nanjing	Jiangsu
China	Shanghai Chest Hospital ( Site 0112)	Shanghai	Shanghai
China	Zhongshan Hospital Fudan University ( Site 0100)	Shanghai	Shanghai
China	1st Affil Hosp of Med College of Xi'an Jiaotong University ( Site 0103)	XiAn	Shanxi
Colombia	Biomelab S A S ( Site 0365)	Barranquilla	Atlantico
Colombia	Centro Medico Imbanaco de Cali S.A ( Site 0369)	Cali	Valle Del Cauca
Colombia	Fundacion Centro de Investigacion Clinica CIC ( Site 0366)	Medellin	Antioquia
Colombia	Hospital General de Medellin Luz Castro de Gutierrez ( Site 0368)	Medellin	Antioquia
Colombia	Oncomedica S.A. ( Site 0372)	Monteria	Cordoba
Colombia	Sociedad de Oncología Y Hematología del Cesar S.A.S. ( Site 0374)	Valledupar	Cesar
Estonia	SA Pohja-Eesti Regionaalhaigla ( Site 0162)	Tallin	Harjumaa
Estonia	AS Ida-Tallinna Keskhaigla ( Site 0161)	Tallinn	Harjumaa
Estonia	SA Tartu Ulikooli Kliinikum ( Site 0160)	Tartu	Tartumaa
France	CHU Amiens Sud ( Site 0182)	Amiens	Somme
France	Centre Hospitalier de la Cote Basque ( Site 0173)	Bayonne	Pyrenees-Atlantiques
France	CHU Jean Minjoz ( Site 0167)	Besancon	Doubs
France	CHU de Grenoble - Hopital Michallon ( Site 0169)	La Tronche	Isere
France	ICM Val D Auerelle ( Site 0177)	Montpellier	Herault
France	Institut Curie ( Site 0166)	Paris
France	CHU de Rouen ( Site 0174)	Rouen	Seine-Maritime
France	Institut de Cancerologie de l Ouest Centre Rene Gauducheau ( Site 0185)	Saint Herblain	Loire-Atlantique
France	Institut Curie - Centre Rene Huguenin ( Site 0181)	Saint-Cloud	Hauts-de-Seine
France	Centre hospitalier Toulon Sainte-Musse ( Site 0172)	Toulon	Var
Hungary	Semmelweis Egyetem ( Site 0210)	Budapest
Hungary	Petz Aladar Megyei Oktato Korhaz ( Site 0213)	Gyor	Gyor-Moson-Sopron
Hungary	Bekes Megyei Kozponti Korhaz - Pandy Kalman Tagkorhaza ( Site 0207)	Gyula	Bekes
Hungary	Somogy Megyei Kaposi Mor Oktato Korhaz ( Site 0217)	Kaposvar
Hungary	Borsod-Abauj-Zemplen Megyei Kozponti Korhaz es Egyetemi Oktatokorhaz ( Site 0202)	Miskolc	Borsod-Abauj-Zemplen
Hungary	CRU Hungary KFT ( Site 0209)	Miskolc	Borsod-Abauj-Zemplen
Hungary	Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet ( Site 0203)	Szolnok	Jasz-Nagykun-Szolnok
Hungary	Tudogyogyintezet Torokbalint ( Site 0205)	Torokbalint	Pest
Israel	Barzilai Medical Center ( Site 0226)	Ashkelon	?eifa
Israel	Soroka Medical Center ( Site 0222)	Beer Sheva
Israel	Bnei Zion Medical Center ( Site 0227)	Haifa	Heifa
Israel	Rambam Medical Center ( Site 0223)	Haifa
Israel	Meir Medical Center ( Site 0221)	Kfar-Saba
Israel	Rabin Medical Center ( Site 0224)	Petah Tikva
Israel	Sheba Medical Center ( Site 0220)	Ramat Gan	Tel Aviv
Israel	Sourasky Medical Center ( Site 0225)	Tel Aviv
Italy	Azienda Ospedaliera San Giuseppe Moscati ( Site 0234)	Avellino
Italy	Centro di Riferimento Oncologico CRO ( Site 0235)	Aviano	Pordenone
Italy	Universita Magna Grecia ( Site 0230)	Catanzaro
Italy	A.O. Universitaria Careggi ( Site 0236)	Firenze
Italy	Ospedale Santa Maria delle Croci ( Site 0232)	Ravenna
Italy	Azienda Ospedaliera S. Giovanni Addolorata-Oncologia Medica ( Site 0233)	Roma	Lazio
Italy	Policlinico Gemelli di Roma ( Site 0237)	Roma
Italy	Presidio Ospedaliero San Vincenzo ( Site 0231)	Taormina	Messina
Japan	Hyogo Cancer Center ( Site 0021)	Akashi	Hyogo
Japan	Kyushu University Hospital ( Site 0030)	Fukuoka
Japan	National Hospital Organization Kyushu Medical Center ( Site 0015)	Fukuoka
Japan	Kurume University Hospital ( Site 0025)	Kurume	Fukuoka
Japan	Aichi Cancer Center Hospital ( Site 0018)	Nagoya	Aichi
Japan	Miyagi Cancer Center ( Site 0028)	Natori	Miyagi
Japan	Okayama University Hospital ( Site 0020)	Okayama
Japan	Osaka International Cancer Institute ( Site 0019)	Osaka
Japan	Kindai University Hospital ( Site 0017)	Osakasayama	Osaka
Japan	National Hospital Organization Kinki-chuo Chest Medical Center ( Site 0027)	Sakai	Osaka
Japan	Sendai Kousei Hospital ( Site 0022)	Sendai	Miyagi
Japan	Juntendo University Hospital ( Site 0029)	Tokyo
Japan	Nippon Medical School Hospital ( Site 0024)	Tokyo
Japan	Toranomon Hospital ( Site 0016)	Tokyo
Japan	Kanagawa Cancer Center ( Site 0023)	Yokohama	Kanagawa
Japan	Kanagawa Cardiovascular and Respiratory Center ( Site 0026)	Yokohama	Kanagawa
Korea, Republic of	Chungbuk National University Hospital ( Site 0079)	Cheongju si	Chungbuk
Korea, Republic of	Seoul National University Bundang Hospital ( Site 0075)	Seongnam-si	Kyonggi-do
Korea, Republic of	Asan Medical Center ( Site 0076)	Seoul
Korea, Republic of	SMG-SNU Boramae Medical Center ( Site 0078)	Seoul
Korea, Republic of	Ulsan University Hospital ( Site 0077)	Ulsan	Ulsan-Kwangyokshi
Malaysia	Hospital Pulau Pinang. ( Site 0065)	Georgetown	Pulau Pinang
Malaysia	University Malaya Medical Centre ( Site 0061)	Kuala Lumpur
Malaysia	Hospital Tengku Ampuan Afzan ( Site 0062)	Kuantan	Pahang
Malaysia	Sarawak General Hospital ( Site 0064)	Kuching	Sarawak
Malaysia	Beacon Hospital Sdn Bhd ( Site 0067)	Petaling Jaya	Selangor
Malaysia	Gleneagles Penang ( Site 0066)	Pulau Pinang
Malaysia	Institut Kanser Negara - National Cancer Institute ( Site 0063)	Putrajaya	Wilayah Persekutuan Putrajaya
Mexico	Consultorios de Medicina Especializada del Sector Privado ( Site 0388)	Guadalajara	Jalisco
Mexico	Centro de Estudios de Investigacion Metabolicos y Cardiovasculares ( Site 0381)	Madero	Tamaulipas
Mexico	Instituto Nacional de Cancerologia. ( Site 0382)	Mexico City
Mexico	Medica Sur S.A.B de C.V. ( Site 0384)	Mexico City	Distrito Federal
Mexico	Oaxaca Site Management Organization SC ( Site 0389)	Oaxaca
Poland	Krakowski Szpital Specjalistyczny im Jana Pawla II ( Site 0253)	Krakow	Malopolskie
Poland	Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie ( Site 0243)	Krakow	Malopolskie
Poland	SPZOZ USK nr 1 im. Norberta Barlickiego UM w Lodzi ( Site 0256)	Lodz	Lodzkie
Poland	Centrum Medyczne Pratia Ostroleka ( Site 0242)	Ostroleka	Mazowieckie
Poland	Ars Medical Sp. z o.o. ( Site 0254)	Pila	Wielkopolskie
Poland	Wojewodzki Szpital im. Sw. Ojca Pio w Przemyslu ( Site 0250)	Przemysl	Podkarpackie
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie ( Site 0252)	Warszawa	Mazowieckie
Poland	Szpital Uniwersytecki im. Karola Marcinkowskiego ( Site 0247)	Zielona Gora	Lubuskie
Russian Federation	Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 0269)	Kazan	Tatarstan, Respublika
Russian Federation	Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 0266)	Krasnoyarsk	Krasnoyarskiy Kray
Russian Federation	City Clinical Oncology Center ( Site 0260)	Saint Petersburg	Sankt-Peterburg
Russian Federation	Railway Hospital of OJSC ( Site 0268)	Saint Petersburg	Sankt-Peterburg
Russian Federation	SBHI Leningrad Regional Clinical Hospital ( Site 0263)	Saint Petersburg	Sankt-Peterburg
Russian Federation	SBHI Samara Regional Clinical Oncology Dispensary ( Site 0265)	Samara	Samarskaya Oblast
Russian Federation	Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 0262)	Ufa	Baskortostan, Respublika
Taiwan	National Taiwan University Hospital Hsin-Chu Branch ( Site 0087)	Hsinchu
Taiwan	Taipei Medical University Shuang Ho Hospital ( Site 0090)	New Taipei
Taiwan	National Cheng Kung University Hospital ( Site 0086)	Tainan
Taiwan	Koo Foundation Sun Yat-Sen Cancer Center ( Site 0091)	Taipei
Taiwan	National Taiwan University Hospital ( Site 0088)	Taipei
Taiwan	Taipei Veterans General Hospital ( Site 0089)	Taipei
Turkey	Abdurrahman Yurtaslan Onkoloji Hastanesi ( Site 0318)	Ankara
Turkey	Baskent Universitesi Ankara Hastanesi ( Site 0319)	Ankara
Turkey	Gulhane Egitim ve Arastirma Hastanesi ( Site 0316)	Ankara
Turkey	Akdeniz Universitesi Tip Fakultesi ( Site 0322)	Antalya
Turkey	Antalya Memorial Hospital Department of Medical Oncology ( Site 0324)	Antalya
Turkey	Dokuz Eylul Universitesi Arastirma Uygulama Hastanesi ( Site 0314)	Izmir
Turkey	Necmettin Erbakan Universitesi Meram Tip Fakultesi ( Site 0321)	Konya	Adana
Turkey	Sakarya Universitesi Egitim ve Arastirma Hastanesi ( Site 0323)	Sakarya
Turkey	Samsun Medical Park Hastanesi ( Site 0320)	Samsun
Ukraine	Cherkasy Regional Hospital ( Site 0336)	Cherkasy	Cherkaska Oblast
Ukraine	City Clinical Hosp.4 of DCC ( Site 0338)	Dnipro	Dnipropetrovska Oblast
Ukraine	MI Precarpathian Clinical Oncology Center ( Site 0346)	Ivano-Frankivsk	Ivano-Frankivska Oblast
Ukraine	Regional Centre of Oncology-Thoracic organs ( Site 0337)	Kharkiv	Kharkivska Oblast
Ukraine	Ukranian Center of TomoTherapy ( Site 0344)	Kropyvnytskiy	Kirovohradska Oblast
Ukraine	Kyiv City Clinical Oncology Centre ( Site 0339)	Kyiv	Kyivska Oblast
Ukraine	Medical and Diagnostic Centre LLC Dobryi Prognoz ( Site 0331)	Kyiv	Kyivska Oblast
Ukraine	Medical Center Verum ( Site 0334)	Kyiv	Kyivska Oblast
Ukraine	Lviv State Oncology Regional Treatment and Diagnostic Center ( Site 0341)	Lviv	Lvivska Oblast
Ukraine	MI Odessa Regional Oncological Centre ( Site 0333)	Odesa	Odeska Oblast
Ukraine	Podillya Regional Center of Oncology ( Site 0343)	Vinnytsia	Vinnytska Oblast
United States	Alaska Clinical Research Center ( Site 0511)	Anchorage	Alaska
United States	Anne Arundel Medical Center Oncology and Hematology ( Site 0514)	Annapolis	Maryland
United States	CBCC Global Research, Inc. ( Site 0532)	Bakersfield	California
United States	Billings Clinic Cancer Center ( Site 0508)	Billings	Montana
United States	Ironwood Cancer & Research Centers ( Site 0541)	Chandler	Arizona
United States	University of Missouri Health Care ( Site 0555)	Columbia	Missouri
United States	Parkview Cancer Center ( Site 0542)	Fort Wayne	Indiana
United States	Cone Health Cancer Center at Alamance Regional ( Site 0527)	Greensboro	North Carolina
United States	Scripps Cancer Center ( Site 0521)	La Jolla	California
United States	University of Kentucky School of Medicine & Hospitals ( Site 0517)	Lexington	Kentucky
United States	Northwest Georgia Oncology Centers PC ( Site 0518)	Marietta	Georgia
United States	Florida Hospital ( Site 0526)	Orlando	Florida
United States	Illinois Cancer Care, PC ( Site 0557)	Peoria	Illinois
United States	Oregon Health Sciences University ( Site 0544)	Portland	Oregon
United States	Park Nicollet Frauenshuh Cancer Center ( Site 0554)	Saint Louis Park	Minnesota
United States	Central Texas Veterans Healthcare System ( Site 0533)	Temple	Texas
United States	Munson Medical Center ( Site 0512)	Traverse City	Michigan
United States	Genesis Cancer Care Center ( Site 0559)	Zanesville	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC	Eisai Inc.

Countries where clinical trial is conducted

United States,  Australia,  Canada,  China,  Colombia,  Estonia,  France,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Mexico,  Poland,  Russian Federation,  Taiwan,  Turkey,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	PFS was defined as the time from date of randomization to the date of the first documentation of progressive disease (PD) or death from any cause, whichever occurred first. Per RECIST 1.1, PD was 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 new lesions was also considered PD. Data are from the product-limit (Kaplan-Meier) method for censored data. PFS as assessed by blinded independent central review (BICR) per RECIST 1.1 is presented.	Up to approximately 25 months
Primary	Overall Survival (OS)	OS was defined as the time from date of randomization to date of death from any cause. OS is presented.	Up to approximately 25 months
Secondary	Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	ORR was defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. ORR as assessed by BICR per RECIST 1.1 is presented.	Up to approximately 25 months
Secondary	Number of Participants Who Experience an Adverse Event (AE)	An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience an AE will be presented.	Through 90 days post last dose of study treatment (Up to approximately 27 months)
Secondary	Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)	The number of participants who discontinue study treatment due to an AE will be presented.	Through last dose of study treatment (Up to approximately 24 months)
Secondary	Change From Baseline in Global Health Status (GHS) (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 [EORTC QLQ-C30] Item 29) Score	The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the question "How would you rate your overall health 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. The change from baseline in GHS (EORTC QLQ-C30 Item 29) score will be presented. A higher score indicates a better overall GHS.	Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months)
Secondary	Change From Baseline in Quality of Life (QoL) (EORTC QLQ-C30 Item 30) Score	The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the question " 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. The change from baseline in QoL (EORTC QLQ-C30 Item 30) score will be presented. A higher score indicates a better overall QoL.	Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months)
Secondary	Change From Baseline in Cough (EORTC Quality of Life Questionnaire-Lung Cancer Module 13 [QLQ-LC13] Item 31) Score	The EORTC QLQ-LC13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30. Participant responses to the question "How much did you cough?" 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. The change from baseline in cough (EORTC QLQ-LC13 Item 31) score will be presented. A lower score indicates a better outcome.	Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months)
Secondary	Change From Baseline in Chest Pain (EORTC QLQ-LC13 Item 40) Score	The EORTC QLQ-LC13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30. 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. The change from baseline in chest pain (EORTC QLQ-LC13 Item 40) score will be presented. A lower score indicates a better outcome.	Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months)
Secondary	Change From Baseline in Dyspnea (EORTC QLQ-C30 Item 8) Score	The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. 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. The change from baseline in dyspnea (EORTC QLQ-C30 Item 8) score will be presented. A lower score indicates a better outcome.	Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months)
Secondary	Change From Baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) Score	The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. 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. The change from baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) score will be presented. A higher score indicates a better quality of life.	Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months)
Secondary	Time to True Deterioration (TTD) Based on Change From Baseline in Global Health Status (GHS) (EORTC QLQ-C30 Item 29) Score	TTD is defined as the time from Baseline to the first onset of a =10-point negative change (decrease) from Baseline in GHS (EORTC QLQ-C30 Item 29) score. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a =10-point negative change (decrease) from Baseline in GHS score, will be presented. A longer TTD indicates a better outcome.	Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months)
Secondary	Time to True Deterioration (TTD) Based on Change From Baseline in Quality of Life (QoL) (EORTC QLQ-C30 Item 30) Score	TTD is defined as the time from Baseline to the first onset of a =10-point negative change (decrease) from Baseline in QoL (EORTC QLQ-C30 Item 30) score. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a =10-point negative change (decrease) from Baseline in QoL score, will be presented. A longer TTD indicates a better outcome.	Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months)
Secondary	Time to True Deterioration (TTD) Based on Change From Baseline in the Composite Endpoint of Cough (EORTC QLQ-LC13 Item 31), Chest Pain (EORTC QLQ-LC13 Item 40), or Dyspnea (EORTC QLQ-C30 Item 8)	TTD is defined as the time from Baseline to the first onset of a =10-point negative change (decrease) from Baseline in the composite endpoint of cough (QLQ-LC13 item 31), chest pain (QLQ-LC13 item 40), or dyspnea (QLQ-C30 Item 8). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a =10-point negative change (decrease) from Baseline in the composite endpoint of cough, chest pain or dyspnea, will be presented. A longer TTD indicates a better outcome.	Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months)
Secondary	Time to True Deterioration (TTD) Based on Change From Baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score	TTD is defined as the time from Baseline to the first onset of a =10-point negative change (decrease) from Baseline in physical functioning (EORTC QLQ-C30 Items 1-5) score. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a =10-point negative change (decrease) from Baseline in physical functioning score, will be presented.	Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months)

External Links

•   Merck Clinical Trial Information