A Study of Pembrolizumab (MK-3475) With or Without Lenvatinib (E7080/MK-7902) as First Line (1L) Intervention in a Programmed Cell Death-ligand 1 (PD-L1) Selected Population With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC) (LEAP-010) (MK-7902-010)

Head and Neck Squamous Cell Carcinoma Clinical Trial

— LEAP-10  

Official title:

A Phase 3, Randomized, Placebo-controlled, Double-blind Clinical Study of Pembrolizumab (MK-3475) With or Without Lenvatinib (E7080/MK-7902) to Evaluate the Safety and Efficacy of Pembrolizumab and Lenvatinib as 1L Intervention in a PD-L1 Selected Population of Participants With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC) (LEAP-010).

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04199104
• Other study ID #: 7902-010
• Secondary ID: MK-7902-010LEAP-
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: February 5, 2020
• Est. completion date: December 23, 2024

Study information

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

Clinical Trial Summary

This is a study of pembrolizumab (MK-3475) with or without lenvatinib (E7080/MK-7902) as a first line intervention in a PD-L1 selected population with participants with recurrent or metastatic head and neck squamous cell carcinoma.

Hypotheses include:

• Pembrolizumab + lenvatinib is superior to pembrolizumab + placebo with respect to Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR).

• Pembrolizumab + lenvatinib is superior to pembrolizumab + placebo with respect to Progression Free Survival (PFS) per RECIST 1.1 as assessed by BICR.

• Pembrolizumab + lenvatinib is superior to pembrolizumab + placebo with respect to overall survival (OS).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 511
• Est. completion date: December 23, 2024
• Est. primary completion date: May 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Has histologically confirmed diagnosis of R/M HNSCC that is considered incurable by local therapies.

Note: Participants with newly-diagnosed HNSCC must be M1/Stage IV.

• Has a primary tumor location of oropharynx, oral cavity, hypopharynx, or larynx.

Note: Primary tumor site of nasopharynx (any histology) or unknown primary tumor (including p16+ unknown primary) are not eligible.

Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirements above, the local label requirements are to be followed.

• Male participants agree to use approved contraception during the treatment period for at least 7 days after the last dose of lenvatinib/placebo, or refrain from heterosexual intercourse during this period

• Female participants are not pregnant or breastfeeding, and are not a woman of childbearing potential (WOCBP), OR are a WOCBP that agrees to use contraception during the treatment period (or 14 days prior to the initiation of study treatment for oral contraception) and for at least 120 days post pembrolizumab, or 30 days post lenvatinib/placebo, whichever occurs last

• Has measurable disease per RECIST 1.1 as assessed by BICR. Note: Lesions situated in a previously irradiated area are considered measurable if progression has been shown in such lesions.

• Participants with oropharyngeal cancer must have results from testing of human papillomavirus HPV status.

• Has an Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 1.

• Have adequately controlled blood pressure with or without antihypertensive medications.

• Has adequate organ function.

Exclusion Criteria:

• Has a history of any contraindication or has a severe hypersensitivity to any components of pembrolizumab (=Grade 3) or lenvatinib.

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

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

• Has clinically significant cardiovascular impairment within 12 months of the first dose of study intervention, such as history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or cerebrovascular accident/transient ischemic attack (TIA)/stroke, cardiac revascularization, or cardiac arrhythmia associated with hemodynamic instability.

• Has disease that is suitable for local therapy administered with curative intent.

• Had PD within 6 months of completion of curatively intended systemic treatment for locoregionally advanced HNSCC.

• Has had major surgery within 3 weeks before to first dose of study interventions.

• Has difficulty swallowing capsules or ingesting a suspension orally or by a feeding tube.

• Has received prior therapy with lenvatinib or pembrolizumab.

• Received last dose of systemic therapy for locoregionally advanced disease less than 6 months before signing consent.

• 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., CTLA-4, OX-40, CD137).

• Has received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization.

• Has received prior radiotherapy within 2 weeks of start of study intervention.

• Has received a live vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.

• Received an investigational agent or has used an investigational device within 4 weeks prior to study intervention-administration.

• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention.

• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.

Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.

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

• Has an active autoimmune disease that has required systemic treatment in past 2 years. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid) is allowed.

• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.

• Has an active infection requiring systemic therapy. (e.g., tuberculosis, known viral or bacterial infections, etc.).

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

• Has a known history of hepatitis B (defined as HBsAg reactive) or known active hepatitis C virus (defined as HCV ribonucleic acid (RNA) [qualitative] is detected) infection.

• Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study intervention.

• Has had an allogenic tissue/solid organ transplant.

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Head and Neck Squamous Cell Carcinoma
• Squamous Cell Carcinoma of Head and Neck

Intervention

Drug:
• Lenvatinib
Lenvatinib, 20 mg (two 10-mg oral capsules) administered QD

Biological:
• Pembrolizumab
Pembrolizumab (MK-3475), 200 mg, every 3 weeks (Q3W) by intravenous (IV) infusion for up to 35 3-week cycles

Drug:
• Placebo
Lenvatinib-matching placebo, oral capsules, administered once daily (QD)

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital ( Site 1004)	Adelaide	South Australia
Australia	Chris OBrien Lifehouse ( Site 1002)	Camperdown	New South Wales
Australia	St George Hospital ( Site 1001)	Kogarah	New South Wales
Brazil	Oncocentro Ceara ( Site 0412)	Fortaleza	Ceara
Brazil	Fundacao Sao Francisco Xavier ( Site 0409)	Ipatinga	Minas Gerais
Brazil	ELO Pesquisa Clinica ( Site 0405)	Maringa	Parana
Brazil	Hospital de Passo Fundo ( Site 0401)	Passo Fundo	Rio Grande Do Sul
Brazil	Clinica LACKS ( Site 0402)	Pelotas	Rio Grande Do Sul
Brazil	Hospital Nossa Senhora da Conceição-Centro Integrado de Pesquisa em Oncologia ( Site 0414)	Porto Alegre	Rio Grande Do Sul
Brazil	A.C. Camargo Cancer Center ( Site 0407)	Sao Paulo
Canada	McGill University Health Centre ( Site 0206)	Montreal	Quebec
Canada	Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0	Quebec City	Quebec
Canada	Princess Margaret Cancer Centre ( Site 0200)	Toronto	Ontario
China	Beijing Cancer Hospital ( Site 3314)	Beining	Beijing
China	Peking Union Medical College Hospital ( Site 3304)	Bejiing	Beijing
China	Jilin Cancer Hospital ( Site 3310)	Changchun	Jilin
China	Hunan Cancer Hospital ( Site 3311)	Changsha	Hunan
China	Xiangya Hospital of Central South University ( Site 3305)	Changsha	Hunan
China	West China Hospital of Sichuan University ( Site 3308)	Chengdu	Sichuan
China	Chongqing Cancer Hospital ( Site 3327)	Chongqing	Chongqing
China	Fujian Provincial Cancer Hospital ( Site 3326)	Fuzhou	Fujian
China	Guizhou Cancer Hospital ( Site 3330)	Guiyang	Guizhou
China	Zhejiang Cancer Hospital ( Site 3303)	Hangzhou	Zhejiang
China	The Third Affiliated Hospital of Harbin Medical University ( Site 3302)	Harbin	Heilongjiang
China	Jiangxi Cancer Hospital ( Site 3313)	Nanchang	Jiangxi
China	Guangxi Medical University Affiliated Tumor Hospital ( Site 3322)	Nanning	Guangxi
China	Fudan University Shanghai Cancer Center ( Site 3324)	Shanghai	Shanghai
China	Shanghai East Hospital ( Site 3300)	Shanghai	Shanghai
China	Tianjin Medical University Cancer Hospital ( Site 3312)	Tianjin	Tianjin
China	Tongji Hospital Tongji Medical,Science & Technology ( Site 3316)	Wuhan	Hubei
China	Wuhan Union hospital Cancer Center ( Site 3307)	Wuhan	Hubei
China	The First Affiliated Hospital of Xi an Jiaotong University ( Site 3328)	XI An	Shaanxi
China	Henan Cancer Hospital ( Site 3309)	Zhengzhou	Henan
France	Centre Leon Berard ( Site 1901)	Lyon	Auvergne
France	Hopital de la Timone ( Site 1903)	Marseille	Bouches-du-Rhone
France	Centre Henri Becquerel ( Site 1904)	Rouen	Seine-Maritime
France	Hopital Foch ( Site 1905)	Suresnes	Hauts-de-Seine
France	Gustave Roussy ( Site 1906)	Villejuif	Val-de-Marne
Germany	Charite Universitätsmedizin Berlin Campus Benjamin Franklin ( Site 2112)	Berlin
Germany	Universitaetsklinikum Frankfurt ( Site 2107)	Frankfurt	Hessen
Germany	KRH Klinikum Siloah ( Site 2103)	Hannover	Niedersachsen
Germany	Universitaetsklinikum Koeln ( Site 2111)	Koeln	Nordrhein-Westfalen
Germany	Universitätsklinikum Leipzig-Department for ENT ( Site 2106)	Leipzig	Sachsen
Germany	Universitaetsklinikum Regensburg ( Site 2100)	Regensburg	Bayern
Germany	Universitaetsklinikum Tuebingen ( Site 2108)	Tuebingen	Baden-Wurttemberg
Germany	Universitaetsklinikum Ulm ( Site 2102)	Ulm	Baden-Wurttemberg
Hungary	Orszagos Onkologiai Intezet ( Site 2202)	Budapest
Hungary	Uzsoki Utcai Korhaz ( Site 2201)	Budapest	Vas
Hungary	Debreceni Egyetem Klinikai Kozpont ( Site 2206)	Debrecen
Hungary	Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Okta-Klinikai Onkológiai és Sugárterápiás Ce	Miskolc	Borsod-Abauj-Zemplen
Hungary	Szegedi Egyetem Szent-Gyorgyi Albert Klinikai Kozpont ( Site 2207)	Szeged	Csongrad
Hungary	Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet ( Site 2200)	Szolnok	Jasz-Nagykun-Szolnok
Italy	Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia ( Site 2402)	Brescia
Italy	ASST Santi Paolo e Carlo - Presidio Ospedaliero San Paolo ( Site 2405)	Milano
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 2400)	Milano
Italy	IEO Istituto Europeo di Oncologia ( Site 2406)	Milano
Italy	Istituto Oncologico Veneto ( Site 2404)	Padova
Italy	ASL Liguria 2 - Ospedale San Paolo ( Site 2401)	Savona
Japan	Hyogo Cancer Center ( Site 1112)	Akashi	Hyogo
Japan	Chiba cancer center ( Site 1110)	Chiba-shi	Chiba
Japan	National Hospital Organization Kyushu Medical Center ( Site 1111)	Fukuoka
Japan	Hiroshima University Hospital ( Site 1109)	Hiroshima
Japan	National Cancer Center Hospital East ( Site 1100)	Kashiwa	Chiba
Japan	Kagawa University Hospital ( Site 1108)	Kita-gun	Kagawa
Japan	Aichi Cancer Center Hospital ( Site 1113)	Nagoya	Aichi
Japan	Nagoya University Hospital ( Site 1106)	Nagoya	Aichi
Japan	Kindai University Hospital ( Site 1107)	Osakasayama	Osaka
Japan	Shizuoka Cancer Center Hospital and Research Institute ( Site 1105)	Sunto-gun	Shizuoka
Japan	National Cancer Center Hospital ( Site 1102)	Tokyo
Japan	The Cancer Institute Hospital of JFCR ( Site 1103)	Tokyo
Japan	Tokyo Medical and Dental University Hospital ( Site 1101)	Tokyo
Japan	Yokohama City University Hospital ( Site 1104)	Yokohama	Kanagawa
Korea, Republic of	Keimyung University Dongsan Hospital ( Site 1203)	Daegu	Taegu-Kwangyokshi
Korea, Republic of	Chonnam National University Hwasun Hospital ( Site 1202)	Hwasun-gun	Jeonranamdo
Korea, Republic of	Seoul National University Bundang Hospital ( Site 1205)	Seongnam-si	Kyonggi-do
Korea, Republic of	The Catholic University of Korea Eunpyeong St Mary s Hospital ( Site 1204)	Seoul
Korea, Republic of	Asan Medical Center ( Site 1201)	Songpa-gu	Seoul
Korea, Republic of	Ajou University Hospital ( Site 1200)	Suwon-si	Kyonggi-do
Mexico	Centro de Investigacion y Avances Medicos Especializados -CIAME ( Site 0604)	Cancun	Quintana Roo
Mexico	Cryptex Investigación Clínica S.A. de C.V. ( Site 0608)	Cuauhtémoc, Mexico City	Distrito Federal
Mexico	Christus Muguerza Clinica Vidriera ( Site 0607)	Monterrey	Nuevo Leon
Mexico	Hospital Universitario "Dr. Jose Eleuterio Gonzalez" ( Site 0602)	Monterrey	Nuevo Leon
Mexico	Oaxaca Site Management Organization S.C. ( Site 0603)	Oaxaca
Peru	Hospital Nacional Arzobispo Loayza ( Site 0703)	Lima
Peru	Hospital Nacional Cayetano Heredia ( Site 0704)	Lima
Peru	Hospital Nacional Edgardo Rebagliati Martins ( Site 0702)	Lima
Peru	Hospital Nacional Guillermo Almenara Irigoyen ( Site 0700)	Lima
Peru	Instituto Nacional de Enfermedades Neoplasicas ( Site 0701)	Lima	Muni Metro De Lima
Poland	Centrum Onkologii im prof Franciszka Lukaszczyka ( Site 2508)	Bydgoszcz	Kujawsko-pomorskie
Poland	Szpital Morski im. PCK. Szpitale Pomorskie Sp. Z o.o ( Site 2504)	Gdynia	Pomorskie
Poland	Narodowy Instytut Onkologii - Oddzial w Gliwicach ( Site 2506)	Gliwice	Slaskie
Poland	Przychodnia Lekarska Komed ( Site 2500)	Konin	Wielkopolskie
Poland	Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie ( Site 2502)	Krakow	Malopolskie
Poland	Szpital Kliniczny im. Heliodora Swiecickiego Uniwers Medyczn ( Site 2509)	Poznan	Wielkopolskie
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworow Glowy i Szyi ( Site	Warszawa	Mazowieckie
Poland	Dolnoslaskie Centrum Onkologii. ( Site 2507)	Wroclaw	Dolnoslaskie
Russian Federation	Altay Regional Oncology Dispensary ( Site 2611)	Barnaul	Altayskiy Kray
Russian Federation	Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 2609)	Kazan	Tatarstan, Respublika
Russian Federation	FSCC FMBA of Russia ( Site 2603)	Moscow	Moskva
Russian Federation	Yaroslavl Regional SBIH Clinical Oncology Hospital ( Site 2605)	Yaroslavl	Yaroslavskaya Oblast
Spain	H.U. Vall de Hebron ( Site 2700)	Barcelona
Spain	Hospital Duran i Reynals ( Site 2701)	Hospitalet de Llobregat	Barcelona
Spain	Hospital Universitario 12 de Octubre ( Site 2702)	Madrid
Spain	Hospital Universitario La Paz ( Site 2706)	Madrid
Spain	Hospital de Valme ( Site 2705)	Sevilla
Spain	Hospital Clinico Universitario Lozano Blesa ( Site 2703)	Zaragoza
Taiwan	Chang Gung Medical Foundation. Kaohsiung Branch ( Site 1604)	Kaohsiung
Taiwan	MacKay Memorial Hospital ( Site 1602)	Taipei
Taiwan	National Taiwan University Hospital ( Site 1600)	Taipei
Taiwan	Taipei Veterans General Hospital ( Site 1601)	Taipei
Taiwan	National Cheng Kung University Hospital ( Site 1603)	Taiwan	Tainan
Turkey	Ankara Sehir Hastanesi ( Site 2802)	Ankara
Turkey	Hacettepe Universitesi Tip Fakultesi ( Site 2805)	Ankara
Turkey	Trakya Universitesi Tip Fakultesi ( Site 2801)	Edirne
Turkey	Medipol Universite Hastanesi ( Site 2800)	Istanbul
Turkey	Ege Universitesi Tip Fakultesi Hastanesi ( Site 2804)	Izmir
Turkey	Medical Park Izmir Hospital ( Site 2807)	Izmir
Turkey	Inonu Universitesi Turgut Ozal Tip Merkezi ( Site 2803)	Malatya
United Kingdom	Aberdeen Royal Infirmary ( Site 2905)	Aberdeen	Aberdeen City
United Kingdom	Guy's Hospital in London ( Site 2908)	London	London, City Of
United Kingdom	Royal Marsden NHS Foundation Trust ( Site 2910)	London	London, City Of
United Kingdom	Christie NHS Foundation Trust ( Site 2903)	Manchester
United Kingdom	Mount Vernon Cancer Centre ( Site 2902)	Northwood	London, City Of
United Kingdom	Nottingham City Hospital ( Site 2907)	Nottingham	Nottinghamshire
United Kingdom	Royal Marsden Hospital ( Site 2904)	Sutton	London, City Of
United Kingdom	Taunton and Somerset Hospital ( Site 2900)	Taunton	Somerset
United States	University of Michigan ( Site 0064)	Ann Arbor	Michigan
United States	Georgia Cancer Center at Augusta University ( Site 0013)	Augusta	Georgia
United States	University of Colorado Cancer Center ( Site 0023)	Aurora	Colorado
United States	St. Vincent Frontier Cancer Center ( Site 0008)	Billings	Montana
United States	Blue Ridge Cancer Care ( Site 0015)	Blacksburg	Virginia
United States	Dana Farber Cancer Institute ( Site 0019)	Boston	Massachusetts
United States	University of North Carolina- Chapel Hill ( Site 0056)	Chapel Hill	North Carolina
United States	Henry Ford Health System ( Site 0001)	Detroit	Michigan
United States	Karmanos Cancer Institute ( Site 0054)	Detroit	Michigan
United States	Duke Cancer Center ( Site 0044)	Durham	North Carolina
United States	Inova Schar Cancer Institute ( Site 0009)	Fairfax	Virginia
United States	University of Connecticut Health Center ( Site 0020)	Farmington	Connecticut
United States	California Cancer Associates for Research & Excellence ( Site 0025)	Fresno	California
United States	John Theurer Cancer Center at Hackensack University Medical Center ( Site 0002)	Hackensack	New Jersey
United States	Memorial Regional Hospital-Memorial Cancer Institute ( Site 0069)	Hollywood	Florida
United States	University of Louisville, James Graham Brown Cancer Center ( Site 0045)	Louisville	Kentucky
United States	University of Wisconsin- Madison Carbone Cancer Center ( Site 0006)	Madison	Wisconsin
United States	Northwest Georgia Oncology Centers PC ( Site 0028)	Marietta	Georgia
United States	Weill Cornell Medicine New York Presbyterian Hospital ( Site 0040)	New York	New York
United States	Oncology Hematology West, PC dba Nebraska Cancer Specialists ( Site 0053)	Omaha	Nebraska
United States	Providence Portland Medical Center ( Site 0048)	Portland	Oregon
United States	Washington University School of Medicine ( Site 0060)	Saint Louis	Missouri
United States	California Cancer Associates for Research & Excellence ( Site 0059)	San Marcos	California
United States	Cancer Care Northwest ( Site 0017)	Spokane Valley	Washington
United States	SUNY Upstate Medical University ( Site 0051)	Syracuse	New York
United States	University of Kansas Cancer Center ( Site 0033)	Westwood	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC	Eisai Inc.

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Canada,  China,  France,  Germany,  Hungary,  Italy,  Japan,  Korea, Republic of,  Mexico,  Peru,  Poland,  Russian Federation,  Spain,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 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, taking as reference the baseline sum diameters) per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The percentage of participants who experience a CR or PR based on modified RECIST 1.1 will be presented.	Up to approximately 28 months
Primary	Progression Free Survival (PFS) per 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 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.	Up to approximately 39 months
Primary	Overall Survival (OS)	OS is the time from randomization to death due to any cause.	Up to approximately 39 months
Secondary	Duration of Response (DOR)	For participants who demonstrate a confirmed complete response (CR: Disappearance of all target lesions) or confirmed Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until disease progression or death.	Up to approximately 39 months
Secondary	Number of Participants Who Experienced an Adverse Event (AE)	An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.	Up to approximately 50 months
Secondary	Number of Participants Who Discontinued Study Drug Due to an AE	An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.	Up to approximately 50 months

External Links

•   Merck Clinical Trials Information