Efficacy and Safety of Pembrolizumab (MK-3475) With Lenvatinib (E7080/MK-7902) vs. Docetaxel in Participants With Metastatic Non-Small Cell Lung Cancer (NSCLC) and Progressive Disease (PD) After Platinum Doublet Chemotherapy and Immunotherapy (MK-7902-008/E7080-G000-316/LEAP-008)

Metastatic Non-Small Cell Lung Cancer Clinical Trial

Official title:

A Phase 3, Multicenter, Randomized, Open-label Trial to Compare the Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Lenvatinib (E7080/MK-7902) Versus Docetaxel in Previously Treated Participants With Metastatic Non-small Cell Lung Cancer (NSCLC) and Progressive Disease (PD) After Platinum Doublet Chemotherapy and Immunotherapy (LEAP-008)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03976375
• Other study ID #: 7902-008
• Secondary ID: MK-7902-008LEAP-
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 26, 2019
• Est. completion date: September 18, 2024

Study information

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

Clinical Trial Summary

This study will evaluate the efficacy and safety of pembrolizumab (MK-3475) with lenvatinib (E7080/MK-7902) vs. docetaxel in participants with metastatic non-small cell lung cancer (NSCLC) and progressive disease (PD) after platinum doublet chemotherapy and treatment with one prior anti-PD-1/PD-L1 monoclonal antibody (mAb). The primary hypotheses of this study are that pembrolizumab + lenvatinib (compared with docetaxel) prolongs: 1) overall survival (OS); and progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) based on blinded independent central review (BICR).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 422
• Est. completion date: September 18, 2024
• Est. primary completion date: August 11, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Has a histologically or cytologically confirmed diagnosis of metastatic squamous or nonsquamous NSCLC (Stage IV: M1a, M1b, M1c).

• Has PD on treatment with one prior anti-PD-1/PD-L1 monoclonal antibody (mAb) administered either as monotherapy or in combination with other checkpoint inhibitors or other therapies.

• Retreatment with the same anti-PD-L1/PD-L1 mAb is acceptable in the overall course of treatment

• Has PD during/after platinum doublet chemotherapy for metastatic disease.

• Has confirmation that EGFR-, ALK-, or ROS1-directed therapy is not indicated as primary therapy (documentation of absence of tumor-activating EGFR mutations [eg, DEL19 or L858R], and absence of ALK and ROS1 gene rearrangements OR presence of a K-ras mutation).

• Has submitted pre-study imaging that confirmed evidence of PD following initiation of an anti-PD-1/PD-L1 inhibitor.

• Has at least 1 measurable lesion by computerized tomography (CT) or magnetic resonance imaging (MRI) per RECIST 1.1, as determined by the local site assessment.

• Has provided tumor tissue for PD-L1 biomarker analysis from an archival sample (defined as: from initial diagnosis of NSCLC and prior to receiving immunotherapy [antiPD-1/PD-L1], from the primary lesion or a metastatic lesion).

• Has provided prior to allocation tissue from a newly obtained formalin-fixed sample from a new biopsy (defined as: after completion of immunotherapy [anti-PD-1/PD-L1] and before receiving a randomization number), of a tumor lesion not previously irradiated.

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

• Has a life expectancy of at least 3 months.

• Male participants receiving pembrolizumab ± lenvatinib or lenvatinib must agree to refrain from donating sperm, and either 1) be abstinent from heterosexual intercourse; or 2) follow contraceptive guidance during the treatment period or 7 days after the last dose of lenvatinib. Male participants receiving docetaxel agree to adhere to the same conditions during the treatment period and for =90 days after the last dose of study treatment.

• Female participants must not be pregnant, not be breastfeeding, and not be a woman of child-bearing potential (WOCBP). If a WOCBP, agrees to not donate eggs and either use contraception, or be abstinent from heterosexual intercourse during the treatment period and for =120 days after the last dose of pembrolizumab or 30 days after the last dose of lenvatinib, whichever occurs last. If a WOCBP receiving docetaxel, agrees to adhere to the same conditions during the treatment period and for =30 days after the last dose of study treatment.

• 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.

• If participant received major surgery or radiation therapy of >30 Gy, they have recovered from the toxicity and/or complications from the intervention.

• Has adequate organ function.

Exclusion Criteria:

• Has received docetaxel as monotherapy or in combination with other therapies.

• Has received lenvatinib as monotherapy or in combination with an anti-PD-1/PD-L1 mAb.

• Has received: 1) radiotherapy within 2 weeks before the first dose of study treatment; or 2) lung radiation therapy >30 Gy within 6 months before the first dose of study treatment.

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

• Has clinically significant hemoptysis or tumor bleeding within 2 weeks before the first dose of study treatment.

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

• Has clinically significant cardiovascular impairment within 12 months of the first dose of study treatment.

• Has a history of a gastrointestinal condition or procedure that may affect oral absorption of study treatment.

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

• Is currently participating in a clinical trial and receiving study therapy or participated in a study of an investigational agent within 4 weeks of the first dose of study treatment.

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

• Has a known history of an additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of disease recurrence for 3 years since initiation of that therapy.

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

• Has severe hypersensitivity to pembrolizumab and/or any of its excipients.

• Has a sensitivity to any of the excipients contained in lenvatinib and/or docetaxel.

• Has an active autoimmune disease that has required systemic treatment in the past 2 years.

• Has a history of (noninfectious) pneumonitis that required systemic steroids or 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 reactive or known active hepatitis C virus infection.

• Has active tuberculosis.

• 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 pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through at least 120 days after the last dose of pembrolizumab or lenvatinib, or 90 days (male participants) or 30 days (for female participants) after the last dose of docetaxel.

• Has had an allogeneic tissue/solid organ transplant.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Disease Progression
• Lung Neoplasms
• Metastatic Non-Small Cell Lung Cancer

Intervention

Biological:
• Pembrolizumab
IV infusion of pembrolizumab at 200 mg

Drug:
• Lenvatinib
Oral capsules (unit strength: 4 and 10 mg) at 20 mg or 24 mg total daily dose.
• Docetaxel
IV infusion of docetaxel at 75 mg/m^2.

Locations

Country	Name	City	State
Argentina	CEMIC ( Site 2003)	Buenos Aires
Argentina	Hospital Aleman ( Site 2000)	Buenos Aires
Argentina	Hospital Britanico de Buenos Aires ( Site 2002)	Buenos Aires	Caba
Argentina	Instituto de Investigaciones Metabolicas ( Site 2004)	Caba	Buenos Aires
Argentina	Sanatorio Parque ( Site 2005)	Rosario	Santa Fe
Australia	Bendigo Cancer Centre ( Site 0008)	Bendigo	Victoria
Australia	Blacktown Hospital ( Site 0004)	Blacktown	New South Wales
Australia	Calvary Central Districts Hospital ( Site 0007)	Elizabeth Vale	South Australia
Australia	Port Macquarie Base Hospital ( Site 0003)	Port Macquarie	New South Wales
Australia	Westmead Hospital ( Site 0005)	Westmead	New South Wales
Australia	Southern Medical Day Care Centre ( Site 0001)	Wollongong	New South Wales
Australia	Princess Alexandra Hospital - Division of Cancer Services ( Site 0002)	Woolloongabba	Queensland
Canada	Kingston Health Sciences Centre ( Site 1503)	Kingston	Ontario
Canada	London Regional Cancer Program - London HSC ( Site 1505)	London	Ontario
Canada	CIUSSS Ouest de l Ile - St-Mary s Hospital ( Site 1501)	Montreal	Quebec
Canada	CHUQ-Univ Laval-Hotel Dieu de Quebec ( Site 1514)	Quebec
Canada	Princess Margaret Cancer Centre ( Site 1502)	Toronto	Ontario
Canada	CancerCare Manitoba ( Site 1504)	Winnipeg	Manitoba
Colombia	Clinica de la Costa Ltda. ( Site 1309)	Barranquilla	Atlantico
Colombia	Administradora Country SA - Clinica del Country ( Site 1307)	Bogota	Distrito Capital De Bogota
Colombia	Clinica Colsanitas S.A. Sede Clinica Universitaria Colombia ( Site 1304)	Bogota	Distrito Capital De Bogota
Colombia	Centro Medico Imbanaco de Cali S.A ( Site 1301)	Cali	Valle Del Cauca
Colombia	Rodrigo Botero SAS ( Site 1300)	Medellin	Antioquia
Colombia	Oncomedica S.A. ( Site 1302)	Monteria	Cordoba
Colombia	Sociedad de Oncología Y Hematología del Cesar S.A.S. ( Site 1305)	Valledupar	Cesar
France	ICO Centre Paul Papin ( Site 0412)	Angers	Maine-et-Loire
France	Centre Hospitalier General - Avignon ( Site 0407)	Avignon	Provence-Alpes-Cote-d Azur
France	Clinique Ambroise Pare ( Site 0402)	Beuvry	Pas-de-Calais
France	CHU Caen Service de Pneumologie ( Site 0401)	Caen	Calvados
France	HIA Percy-Clamart ( Site 0411)	Clamart	Hauts-de-Seine
France	Centre Hospitalier Le Mans ( Site 0406)	Le Mans	Sarthe
France	Hopital Europeen Georges Pompidou ( Site 0408)	Paris
France	Institut Curie ( Site 0400)	Paris
Germany	Vivantes Klinikum Spandau ( Site 0505)	Berlin
Germany	SRH Wald-Klinikum Gera GmbH ( Site 0503)	Gera	Thuringen
Germany	Evangelisches Krankenhaus Hamm gGmbH ( Site 0504)	Hamm	Nordrhein-Westfalen
Germany	Thoraxklinik Heidelberg gGmbH am Universitaetsklinikum Heidelberg ( Site 0501)	Heidelberg	Baden-Wurttemberg
Greece	General Hospital of Chest Diseases "Sotiria" ( Site 1703)	Athens	Attiki
Greece	Metropolitan Hospital-4th Oncology Dept ( Site 1700)	Athens	Attiki
Greece	University Hospital of Ioannina ( Site 1701)	Ioannina
Greece	European Interbalkan Medical Center ( Site 1704)	Thessaloniki
Hungary	Orszagos Koranyi Pulmonologiai Intezet ( Site 0603)	Budapest
Hungary	Orszagos Koranyi Pulmonologiai Intezet ( Site 0608)	Budapest
Hungary	Semmelweis Egyetem.. ( Site 0604)	Budapest
Hungary	Veszprem Megyei Tudogyogyintezet ( Site 0607)	Farkasgyepu	Veszprem
Hungary	Petz Aladar Megyei Oktato Korhaz ( Site 0609)	Gyor	Gyor-Moson-Sopron
Hungary	Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Oktatókórház ( Site 0601)	Miskolc	Borsod-Abauj-Zemplen
Hungary	Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz ( Site 0606)	Szekesfehervar	Fejer
Hungary	Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet ( Site 0610)	Szolnok	Jasz-Nagykun-Szolnok
Hungary	Tudogyogyintezet Torokbalint ( Site 0602)	Torokbalint	Pest
Israel	Soroka Medical Center ( Site 0701)	Beer Sheva
Israel	Rambam Medical Center ( Site 0703)	Haifa
Israel	Shaare Zedek Medical Center-Oncology ( Site 0706)	Jerusalem
Israel	Meir Medical Center ( Site 0702)	Kfar-Saba
Israel	Rabin Medical Center ( Site 0700)	Petah Tikva
Israel	Chaim Sheba Medical Center ( Site 0704)	Ramat Gan
Israel	Sourasky Medical Center (Ichilov) - Oncology Clinic ( Site 0705)	Tel Aviv
Italy	Azienda Ospedaliera San Giuseppe Moscati ( Site 0809)	Avellino
Italy	IRCCS Giovanni Paolo II. Ospedale Oncologico ( Site 0808)	Bari
Italy	AOU Policlinico Vittorio Emanuele ( Site 0811)	Catania
Italy	Istituto Nazionale dei Tumori ( Site 0806)	Milano
Italy	Ospedale San Gerardo - ASST Monza ( Site 0804)	Monza	Monza E Brianza
Italy	Ospedale San Luigi Gonzaga ( Site 0802)	Orbassano	Torino
Italy	A.O. Ospedali Riuniti Villa Sofia - Cervello P.O. Villa Sofia ( Site 0810)	Palermo	Sicilia
Italy	Policlinico San Matteo - Fondazione IRCCS ( Site 0812)	Pavia
Italy	Azienda Ospedaliera di Perugia ( Site 0805)	Perugia
Italy	Istittuto Nazionale dei Tumori Regina Elena IRCCS - IFO ( Site 0807)	Rome	Roma
Japan	Chiba University Hospital ( Site 0106)	Chiba
Japan	Kansai Medical University Hospital ( Site 0104)	Hirakata	Osaka
Japan	Niigata Cancer Center Hospital ( Site 0101)	Niigata
Japan	Sendai Kousei Hospital ( Site 0107)	Sendai	Miyagi
Japan	National Cancer Center Hospital ( Site 0103)	Tokyo
Japan	The Cancer Institute Hospital of JFCR ( Site 0100)	Tokyo
Japan	Kanagawa Cardiovascular and Respiratory Center ( Site 0105)	Yokohama	Kanagawa
Korea, Republic of	Chungbuk National University Hospital ( Site 0201)	Cheongju si	Chungbuk
Korea, Republic of	Seoul National University Bundang Hospital ( Site 0204)	Seongnam-si	Kyonggi-do
Korea, Republic of	Severance Hospital Yonsei University Health System ( Site 0202)	Seoul
Korea, Republic of	Asan Medical Center ( Site 0203)	Songpagu	Seoul
Portugal	Centro Hospitalar Lisboa Norte E.P.E. - Hospital Pulido Valente ( Site 1801)	Lisboa
Portugal	Hospital CUF Porto ( Site 1802)	Porto
Portugal	Inst. Portugues de Oncologia de Porto Francisco Gentil EPE ( Site 1800)	Porto
Puerto Rico	Hematology and Oncology Institute ( Site 2105)	Manati
Puerto Rico	Ad-Vance Medical Research LLC ( Site 2103)	Ponce
Puerto Rico	Puerto Rico Medical Research Center LLC ( Site 2101)	San Juan
Russian Federation	Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 0918)	Krasnoyarsk	Krasnoyarskiy Kray
Russian Federation	Central Clinical Hospital of the Administration of the President ( Site 0910)	Moscow	Moskva
Russian Federation	Main Military Clinical Hospital n.a. N.N.Burdenko ( Site 0905)	Moscow	Moskva
Russian Federation	Budgetary Healthcare Institution of Omsk Region Clinical Oncology Dispensary-Chemotherapy #1 ( Site	Omsk	Omskaya Oblast
Russian Federation	SPb SBHI City Clinical Oncological Dispensary ( Site 0901)	Saint Petersburg	Sankt-Peterburg
Russian Federation	Railway Hospital of OJSC ( Site 0907)	Saint-Petersburg	Sankt-Peterburg
Russian Federation	Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 0903)	Saint-Petersburg	Sankt-Peterburg
Russian Federation	GBUZ SPb CRPCstmc(o) ( Site 0921)	Sankt- Peterburg	Sankt-Peterburg
Russian Federation	Pavlov First Saint Petersburg State Medical University ( Site 0917)	St. Petersburg	Sankt-Peterburg
Russian Federation	GBUZ Republican Clinical Oncological Dispensary ( Site 0922)	Ufa	Baskortostan, Respublika
Spain	Hospital Universitari Vall d Hebron ( Site 1004)	Barcelona
Spain	Hospital Ciudad de Jaen ( Site 1000)	Jaen
Spain	Hospital Universitario Insular de Gran Canaria ( Site 1011)	Las Palmas de Gran Canaria	Las Palmas
Spain	Hospital Universitario 12 de Octubre ( Site 1006)	Madrid
Spain	Hospital Universitario Fundacion Jimenez Diaz ( Site 1005)	Madrid
Spain	Hospital Universitario Puerta de Hierro ( Site 1007)	Majadahonda	Madrid
Spain	Consorci Hospitalari Mataro ( Site 1008)	Mataro	Barcelona
Spain	Hospital Central de Asturias ( Site 1002)	Oviedo	Asturias
Spain	Hospital Universitario Quiron Madrid ( Site 1012)	Pozuelo de Alarcon	Madrid
Spain	Hospital Universitario Marques de Valdecilla ( Site 1003)	Santander	Cantabria
Spain	Hospital Clinico de Valencia ( Site 1010)	Valencia	Valenciana, Comunitat
United Kingdom	Aberdeen Royal Infirmary ( Site 1114)	Aberdeen	Scotland
United Kingdom	Birmingham Heartlands Hospital ( Site 1103)	Birmingham
United Kingdom	Hull & East Yorkshire NHS Trust. Castle Hill Hospital ( Site 1108)	Cottingham	East Riding Of Yorkshire
United Kingdom	University Hospital Coventry and Warwickshire NHS Trust ( Site 1112)	Coventry	Warwickshire
United Kingdom	St James s University Hospital ( Site 1106)	Leeds
United Kingdom	Leicester Royal Infirmary ( Site 1110)	Leicester	Leicestershire
United Kingdom	Guy s and St Thomas Hospital NHS Foundation Trust ( Site 1102)	London	London, City Of
United Kingdom	North Middlesex University Hospital NHS Trust ( Site 1109)	London	London, City Of
United Kingdom	Mount Vernon Cancer Centre ( Site 1107)	Northwood	London, City Of
United Kingdom	Nottingham City Hospital Campus ( Site 1105)	Nottingham	England
United States	Comprehensive Blood & Cancer Center [Bakersfield, CA] ( Site 1604)	Bakersfield	California
United States	Harry & Jeanette Weinberg Cancer Institute ( Site 1626)	Baltimore	Maryland
United States	Medstar Good Samaritan Hospital ( Site 1625)	Baltimore	Maryland
United States	Memorial Sloan-Kettering Cancer Center At Basking Ridge ( Site 1664)	Basking Ridge	New Jersey
United States	Hematology Oncology Clinic ( Site 1680)	Baton Rouge	Louisiana
United States	Billings Clinic ( Site 1631)	Billings	Montana
United States	Massachusetts General Hospital ( Site 1622)	Boston	Massachusetts
United States	Bozeman Health Deaconness Cancer Center ( Site 1632)	Bozeman	Montana
United States	TriHealth Cancer Institute ( Site 1672)	Cincinnati	Ohio
United States	MetroHealth Medical Center ( Site 1694)	Cleveland	Ohio
United States	Memorial Sloan-Kettering Cancer Center at Commack ( Site 1662)	Commack	New York
United States	MGH - North Shore Cancer Center ( Site 1668)	Danvers	Massachusetts
United States	Cancer Specialists of North Florida - Fleming Island ( Site 1675)	Fleming Island	Florida
United States	Memorial Sloan-Kettering Cancer Center at West Harrison ( Site 1666)	Harrison	New York
United States	Millenium Physicians ( Site 1690)	Houston	Texas
United States	Thompson Cancer Survival Center ( Site 1695)	Knoxville	Tennessee
United States	University of Kentucky School of Medicine & Hospitals ( Site 1621)	Lexington	Kentucky
United States	Memorial Sloan-Kettering Cancer Center at Middletown ( Site 1665)	Middletown	New Jersey
United States	Memorial Sloan-Kettering Cancer Center at Montvale ( Site 1667)	Montvale	New Jersey
United States	Memorial Sloan-Kettering Cancer Center ( Site 1661)	New York	New York
United States	The Mass General Cancer Center at Newton-Wellesley ( Site 1692)	Newton	Massachusetts
United States	Mid-Florida Cancer Centers ( Site 1611)	Orange City	Florida
United States	Fox Chase Cancer Center ( Site 1647)	Philadelphia	Pennsylvania
United States	New York Cancer and Blood Specialists ( Site 1696)	Port Jefferson Station	New York
United States	Kaiser Permanente Center for Health Research-Kaiser Permanente Medical Center ( Site 1644)	Portland	Oregon
United States	University of Rochester ( Site 1638)	Rochester	New York
United States	Memorial Sloan Kettering Cancer Center - Nassau ( Site 1670)	Uniondale	New York
United States	University of Massachusetts Medical School ( Site 1693)	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC	Eisai Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Canada,  Colombia,  France,  Germany,  Greece,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  Portugal,  Puerto Rico,  Russian Federation,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	OS is defined as the time from randomization to the date of death due to any cause.	Up to ~48 months
Primary	Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	PFS is defined as the time from randomization to the first documented progressive disease (PD) 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 new lesions is also considered PD. PFS will be assessed by blinded independent central review (BICR) per RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.	Up to ~36 months
Secondary	Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+Lenvatinib vs. Docetaxel	ORR is defined as the percentage of participants 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). ORR will be assessed by BICR per RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.	Up to ~18 months
Secondary	Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+Lenvatinib vs. Lenvatinib Monotherapy	ORR is defined as the percentage of participants 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). ORR will be assessed by BICR per RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.	Up to ~36 months
Secondary	Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	DOR is defined as the time from first documented evidence of 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) until disease progression or death due to any cause, whichever occurs first. DOR will be assessed by BICR per RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.	Up to ~48 months
Secondary	Number of Participants Experiencing an Adverse Event (AE)	An AE is any untoward medical occurrence in a clinical study participant that is 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.	Up to ~79 months
Secondary	Number of Participants Discontinuing Study Treatment Due to an AE	The number of participants who discontinue study treatment due to an AE will be presented.	Up to ~79 months
Secondary	Change from Baseline in European Organization for Research and Treatment (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Combined Global Health Status / Quality of Life (Items 29 & 30) Scale Combined Score	The EORTC QLQ-C30 is a 30-item questionnaire developed to assess the quality of life (QoL) of cancer patients, including a combined global health status (GHS)/QoL (Items 29 and 30) scale. For each item, scores range from 0-100, with higher scores indicating higher GHS/QoL. Per protocol, scores for items 29 and 30 will be averaged to compute a combined GHS/QoL scale score. Change from baseline in the combined GHS/QoL scale score will be presented.	Baseline and Week 12
Secondary	Change from Baseline in EORTC Quality of Life Questionnaire Lung Cancer Module 13 (QLQ-LC13) Cough (Item 31) Scale Score	Used in combination with QLQ-C30, the EORTC QLQ-LC13 is a supplemental lung cancer-specific module, including a single-item scale score for cough (Item 31). 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). Scores are transformed to a range from 0-100, with a lower score indicating a better outcome. The change from baseline in the EORTC QLQ-LC13 cough (Item 31) scale score will be presented.	Baseline and Week 12
Secondary	Change from Baseline in EORTC QLQ-LC13 Chest Pain (Item 40) Scale Score	Used in combination with QLQ-C30, the EORTC QLQ-LC13 is a supplemental lung cancer-specific module, including a single-item scale score for chest pain (Item 40). 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). Scores are transformed to a range from 0-100, with a lower score indicating a better outcome. The change from baseline in the EORTC QLQ-LC13 chest pain (Item 40) scale score will be presented.	Baseline and Week 12
Secondary	Change from Baseline in EORTC QLQ-C30 Dyspnea (Item 8) Scale Score	The EORTC QLQ-C30 is a 30-item questionnaire developed to assess the QoL of cancer patients, including a single-item scale score for dyspnea (Item 8). For this item, individual responses to the question "Were you short of breath?" are given on a 4-point scale (1=Not at all; 4=Very much). Scores are transformed to a range from 0-100, with a lower score indicating a better outcome. The change from baseline in the EORTC QLQ-C30 dyspnea (Item 8) scale score will be presented.	Baseline and Week 12
Secondary	Change from Baseline in EORTC QLQ-C30 Physical Functioning (Items 1 to 5) Scale Combined Score	The EORTC QLQ-C30 is a 30-item questionnaire developed to assess the QoL of cancer patients, including a physical functioning (PF) scale (Items 1 to 5). The PF 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]. Overall PF scores range from 0 to 100, with a lower score indicating a better outcome. The change from Baseline in the EORTC QLQ-C30 PF (Items 1 to 5) scale combined score will be presented.	Baseline and Week 12
Secondary	Time to True Deterioration (TTD) in EORTC QLQ-C30 Combined Global Health Status / Quality of Life (Items 29 & 30) Scale Combined Score	The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the QoL of cancer patients, including a combined GHS/QoL (Items 29 and 30) scale. The TTD in the combined GHS/QoL (Items 29 & 30) scale combined score will be presented, defined as the time to first onset of a =10 point decrease from baseline.	Up to ~48 months
Secondary	Time to True Deterioration (TTD) in EORTC QLQ-LC13 Cough (Item 31) Scale Score	Used in combination with QLQ-C30, the EORTC QLQ-LC13 is a supplemental lung cancer-specific module, including a single-item scale score for cough (Item 31). The TTD in EORTC QLQ-LC13 cough (Item 31) scale score will be presented, defined as the time to first onset of a =10 point decrease from baseline.	Up to ~48 months
Secondary	Time to True Deterioration (TTD) in EORTC QLQ-LC13 Chest Pain (Item 40) Scale Score	Used in combination with QLQ-C30, the EORTC QLQ-LC13 is a supplemental lung cancer-specific module, including a single-item scale score for chest pain (Item 40). The TTD in EORTC QLQ-LC13 chest pain (Item 40) scale score will be presented, defined as the time to first onset of a =10 point decrease from baseline.	Up to ~48 months
Secondary	Time to True Deterioration (TTD) in EORTC QLQ-C30 Dyspnea (Item 8) Scale Score	The EORTC QLQ-C30 is a 30-item questionnaire developed to assess the QoL of cancer patients, including a single-item scale score for dyspnea (Item 8). The TTD in dyspnea (Item 8) scale score will be presented, defined as the time to first onset of a =10 point decrease from baseline.	Up to ~48 months
Secondary	Time to True Deterioration (TTD) in EORTC QLQ-C30 Physical Functioning (Items 1 to 5) Scale Combined Score	The EORTC QLQ-C30 is a 30-item questionnaire developed to assess the QoL of cancer patients, including a physical functioning (PF) scale (Items 1 to 5). The TTD in PF (Items 1 to 5) scale combined score will be presented, defined as the time to first onset of a =10 point decrease from baseline.	Up to ~48 months

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary