Melanoma Clinical Trial

Safety and Efficacy Study of Pembrolizumab (MK-3475) Combined With Lenvatinib (MK-7902/E7080) as First-line Intervention in Adults With Advance Melanoma (MK-7902-003/E7080-G000-312/LEAP-003)

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) as first-line treatment in adults with no prior systemic therapy for their advanced melanoma.

The primary study hypotheses are that: 1) The combination of pembrolizumab and lenvatinib is superior to pembrolizumab and placebo 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 and placebo as assessed by Overall Survival (OS). For this study, RECIST 1.1 has been modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

Has histologically or cytologically confirmed melanoma.
Has unresectable Stage III or Stage IV melanoma, as per American Joint Committee on Cancer guidelines, not amenable to local therapy.

Has been untreated for advanced or metastatic disease except as follows:

Proto-oncogene B-Raf (BRAF) V600 mutation-positive melanoma may have received standard of care targeted therapy as first-line therapy for advanced or metastatic disease. Participants that do not have a BRAF V600 mutation but did receive BRAF or BRAF/MEKi therapy are eligible to participate in this study after discussion with the medical monitor.
Prior adjuvant or neoadjuvant therapy, with targeted therapy or immunotherapy (such as anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], anti-programmed cell death 1 [anti-PD-1] therapy or interferon) will only be permitted if relapse did not occur during active treatment or within 6 months of treatment discontinuation.
Have documentation of BRAF V600-activating mutation status or consent to BRAF V600 mutation testing during the Screening period (participants with BRAF mutation-positive melanoma as well as BRAF wild-type or unknown are eligible).
Has an Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.
Has the presence of ≥1 measurable lesion by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST 1.1.
Provides a tumor biopsy. Participants must submit tumor sample during Screening for confirmation of adequacy of tumor tissue at a central pathology laboratory. Participants who do not submit a tumor tissue sample will not be randomized. The tumor biopsy may not be obtained from a lone target lesion. Confirmation of presence of tumor tissue is not required prior to randomization.
Has resolution of toxic effect(s) of the most recent prior therapy to Grade 1 or less (except alopecia). If participant received major surgery or radiation therapy of >30 Gray (Gy), they must have recovered from the toxicity and/or complications from the intervention.
Male participants must agree to use contraception during the treatment period and for at least 7 days after the last dose of study treatment and refrain from donating sperm during this period. Please note that 7 days after lenvatinib/placebo is stopped, if the participant is on pembrolizumab only, no male contraception measures are needed. Contraception 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.

Female participants must not be pregnant, not breastfeeding, and ≥1 of the following conditions applies:

Not a woman of childbearing potential (WOCBP). OR
A WOCBP who agrees to use study-approved contraception during the treatment period and for at least 120 days after the last dose of study treatment.
The participant (or legally acceptable representative) has provided documented informed consent for the study.
Has adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mmHg at screening and no change in antihypertensive medications within 1 week before Cycle 1 Day 1.
Has adequate organ function.

Exclusion Criteria:

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 before the first dose of study treatment.
Has a known additional malignancy that is progressing or requires active treatment. Exceptions include early stage cancers (carcinoma in situ or Stage 1, non-ulcerated primary melanoma <1 mm in depth with no nodal involvement) treated with curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, or in situ breast cancer that has undergone potentially curative therapy.
Has known active central nervous system metastases and/or carcinomatous meningitis.
Has ocular melanoma.
Has known hypersensitivity to active substances or any of their excipients including previous clinically significant hypersensitivity reaction to treatment with another monoclonal antibody.
Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease-modifying agents, corticosteroids or immunosuppressive drugs). 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.
Has an active infection requiring systemic therapy.
Has known history of human immunodeficiency virus (HIV) infection
Has known history of or is positive for hepatitis B virus or hepatitis C virus infection.
Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
Has a history of active tuberculosis (Bacillus tuberculosis).
Gastrointestinal malabsorption or any other condition that might affect the absorption of lenvatinib.
Has had a major surgery within 3 weeks prior to first dose of study intervention. Note: Adequate wound healing after major surgery must be assessed clinically independent of time elapsed for eligibility.
Has a preexisting Grade ≥3 gastrointestinal or non-gastrointestinal fistula.
Has radiographic evidence of encasement or invasion of major blood vessel, or of intratumoral cavitation.
Has active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study treatment.
Has clinically significant cardiovascular disease from 12 months of the first dose of study treatment including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability.
Has urine protein ≥1 g/24-hour. Note: Participants with ≥2+ (≥100 mg/dL) proteinuria on urine dipstick testing (or urinalysis) will undergo 24-hour urine collection for quantitative assessment of proteinuria.
Prolongation of QTcF interval to >480 ms. Note: If the QTcF is prolonged to >480 ms in the presence of a pacemaker, contact the Sponsor to determine eligibility.
Has left ventricular ejection fraction (LVEF) below the institutional (or local laboratory) normal range, as determined by multigated acquisition scan (MUGA) or echocardiogram.
Has received prior therapy in the adjuvant setting. Note: Targeted therapy, anti-CTLA-4, or anti-PD-1 may be allowed.
Has received prior systemic treatment for unresectable or metastatic melanoma other than targeted therapy as noted in Inclusion Criteria above
Has received prior therapy with a monoclonal antibody, chemotherapy, or an investigational agent or device within 4 weeks or 5 half-lives (whichever is longer) before administration of study treatment or not recovered (≤Grade 1 or at Baseline) from adverse events due to previously administered agents.

Exception to this rule would be use of denosumab, which is not excluded. Note: Participants with alopecia and ≤Grade 2 neuropathy are an exception and may enroll.

Has received prior radiotherapy within 2 weeks of first dose of study treatment (Cycle 1 Day 1). Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
Has received live vaccine within 30 days before the first dose of study treatment.
Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
Has had an allogeneic tissue/solid organ transplant.
Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study.

Study is for people with:

Melanoma

Phase:

Phase 3

Estimated Enrollment:

660

Study ID:

NCT03820986

Recruitment Status:

Active, not recruiting

Sponsor:

Merck Sharp & Dohme LLC

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There are 118 Locations for this study

See Locations Near You

The Angeles Clinic and Research Institute ( Site 0707)
Los Angeles California, 90025, United States
UCSF Helen Diller Family Comprehensive Cancer Center ( Site 0704)
San Francisco California, 30322, United States
California Pacific Medical Center Research Institute ( Site 0705)
San Francisco California, 94115, United States
John Wayne Cancer Institute ( Site 0706)
Santa Monica California, 90404, United States
University of Colorado Cancer Center ( Site 0708)
Aurora Colorado, 80045, United States
Yale Cancer Center ( Site 0709)
New Haven Connecticut, 06510, United States
Baptist MD Anderson Cancer Center ( Site 0767)
Jacksonville Florida, 32207, United States
Mid-Florida Cancer Centers ( Site 0764)
Orange City Florida, 32763, United States
AMG Oncology ( Site 0714)
Park Ridge Illinois, 60068, United States
Illinois Cancer Care, PC ( Site 0765)
Peoria Illinois, 61615, United States
Minnesota Oncology Specialist, PA ( Site 0766)
Fridley Minnesota, 55432, United States
St. Vincent Frontier Cancer Center ( Site 0724)
Billings Montana, 59102, United States
Atlantic Health System ( Site 0768)
Morristown New Jersey, 07960, United States
Valley Hospital ( Site 0749)
Paramus New Jersey, 07652, United States
University of North Carolina - Cancer Hospital ( Site 0751)
Chapel Hill North Carolina, 27514, United States
OHSU Center for Health & Healing ( Site 0731)
Portland Oregon, 97239, United States
Inova Schar Cancer Institute ( Site 0739)
Fairfax Virginia, 22031, United States
Lismore Base Hospital ( Site 0453)
Lismore Australian Capital Territory, 2480, Australia
Melanoma Institute Australia ( Site 0452)
North Sydney New South Wales, 2060, Australia
Westmead Hospital ( Site 0451)
Westmead New South Wales, 2145, Australia
Princess Alexandra Hospital ( Site 0454)
Wooloongabba Queensland, 4102, Australia
Eastern Health ( Site 0457)
Box Hill Victoria, 3128, Australia
Fiona Stanley Hospital ( Site 0456)
Murdoch Western Australia, 6150, Australia
LKH Universitatsklinikum Graz ( Site 0776)
Graz Steiermark, 8036, Austria
Medizinische Universitat Wien ( Site 0778)
Wien , 1090, Austria
PERSONAL - Oncologia de Precisao e Personalizada ( Site 0399)
Belo Horizonte Minas Gerais, 30130, Brazil
Hospital de Caridade de Ijui ( Site 0391)
Ijui Rio Grande Do Sul, 98700, Brazil
Hospital Sao Vicente de Paulo ( Site 0396)
Passo Fundo Rio Grande Do Sul, 99010, Brazil
Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 0397)
Porto Alegre Rio Grande Do Sul, 90610, Brazil
Instituto Nacional de Cancer Hospital do Cancer II ( Site 0394)
Rio de Janeiro , 20220, Brazil
BC Cancer-Kelowna - Sindi Ahluwalia Hawkins Centre ( Site 0661)
Kelowna British Columbia, V1Y 5, Canada
Lions Gate Hospital ( Site 0662)
North Vancouver British Columbia, V7L 2, Canada
Sunnybrook Research Institute ( Site 0654)
Toronto Ontario, M4N 3, Canada
Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0652)
Montreal Quebec, H2W 3, Canada
McGill University Health Centre ( Site 0651)
Montreal Quebec, H4A 3, Canada
Centro Investigación del Cáncer James Lind ( Site 0425)
Temuco Araucania, 47800, Chile
Fundacion Arturo Lopez Perez FALP ( Site 0421)
Santiago Region M. De Santiago, 75009, Chile
Pontificia Universidad Catolica de Chile ( Site 0422)
Santiago Region M. De Santiago, 83300, Chile
Sociedad Medica Aren y Bachero Limitada ( Site 0426)
Santiago Region M. De Santiago, 84203, Chile
Oncocentro ( Site 0424)
Vina del Mar Valparaiso, 25205, Chile
Beijing Cancer Hospital ( Site 0601)
Beijing Beijing, 10003, China
Fujian Provincial Cancer Hospital ( Site 0612)
Fuzhou Fujian, 35001, China
Sun Yat-Sen University Cancer Center ( Site 0602)
Guangzhou Guangdong, 51000, China
Henan Cancer Hospital ( Site 0610)
Zhengzhou Henan, 45000, China
Nanjing Drum Tower Hospital ( Site 0609)
Nanjing Jiangsu, 21000, China
The First Hospital Of Jilin University ( Site 0603)
Chang Chun Jilin, 13002, China
Fudan University Shanghai Cancer Center ( Site 0607)
Shanghai Shanghai, 20003, China
Tianjin Medical University Cancer Institute & Hospital ( Site 0606)
Tianjin Tianjin, 30006, China
Yunnan Cancer Hospital ( Site 0604)
Kunming Yunnan, 43003, China
Sir Run Run Shaw Hospital ( Site 0605)
Hangzhou Zhejiang, 31001, China
Zhejiang Cancer Hospital ( Site 0608)
Hangzhou Zhejiang, 31002, China
Hopital ARCHET 2 ( Site 0009)
Nice Alpes-Maritimes, 06200, France
Hopital La Timone ( Site 0002)
Marseille Bouches-du-Rhone, 13385, France
CHU Dijon Bourgogne ( Site 0010)
Dijon Cote-d Or, 21079, France
Institut Claudius Regaud IUCT Oncopole ( Site 0003)
Toulouse Haute-Garonne, 31059, France
Hopital Ambroise Pare Boulogne ( Site 0007)
Boulogne-Billancourt Hauts-de-Seine, 92100, France
CHRU Lille - Hopital Claude Huriez ( Site 0004)
Lille Nord, 59037, France
CHU de Rouen ( Site 0013)
Rouen Seine-Maritime, 76000, France
Centre Hospitalier Victor Dupouy ( Site 0012)
Argenteuil Val-d Oise, 95100, France
Institut Gustave Roussy ( Site 0001)
Villejuif Val-de-Marne, 94805, France
CHU de la Miletrie Poitiers ( Site 0011)
Poitiers Vienne, 86021, France
Klinik fur Dermatologie Allergologie und Venerologie ( Site 0035)
Hannover Baden-Wurttemberg, 30625, Germany
Universitaetsklinikum Erlangen ( Site 0044)
Erlangen Bayern, 91054, Germany
Universitaetsklinikum Wuerzburg-Department of Dermatology ( Site 0036)
Wuerzburg Bayern, 97080, Germany
Hautkrebszentrum Buxtehude ( Site 0037)
Buxtehude Niedersachsen, 21614, Germany
Universitaetsklinikum Carl Gustav Carus ( Site 0041)
Dresden Sachsen, 01307, Germany
Universitaetsklinikum Leipzig ( Site 0040)
Leipzig Sachsen, 04103, Germany
Universitaetsklinikum Schleswig-Holstein Campus Kiel ( Site 0033)
Kiel Schleswig-Holstein, 24105, Germany
SRH Wald-Klinikum Gera GmbH ( Site 0042)
Gera Thuringen, 07548, Germany
HaEmek Medical Center ( Site 0306)
Afula , 18341, Israel
Soroka Medical Center ( Site 0303)
Beer Sheva , 84571, Israel
Rambam Medical Center ( Site 0301)
Haifa , 31096, Israel
Hadassah Ein Karem Hebrew University Medical Center ( Site 0305)
Jerusalem , 91120, Israel
Rabin Medical Center ( Site 0302)
Petah Tikva , 49414, Israel
Chaim Sheba Medical Center ( Site 0304)
Ramat Gan , 52620, Israel
Sourasky Medical Center ( Site 0307)
Tel Aviv , 64239, Israel
Shamir Medical Center-Assaf Harofeh ( Site 0308)
Zerifin , 70300, Israel
ASST Papa Giovanni XXIII ( Site 0062)
Bergamo Abruzzo, 24127, Italy
Azienda Ospedaliera Universitaria Senese ( Site 0065)
Siena Toscana, 53100, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 0064)
Milano , 20133, Italy
Istituto Europeo di Oncologia ( Site 0067)
Milano , 20141, Italy
Istituto Nazionale Tumori Fondazione Pascale ( Site 0061)
Napoli , 80131, Italy
Istituto Oncologico Veneto ( Site 0063)
Padova , 35128, Italy
Kyungpook National University Chilgok Hospital ( Site 0553)
Daegu Taegu-Kwangyokshi, 41404, Korea, Republic of
Seoul National University Hospital ( Site 0554)
Seoul , 03080, Korea, Republic of
Severance Hospital Yonsei University Health System ( Site 0552)
Seoul , 03722, Korea, Republic of
Samsung Medical Center ( Site 0551)
Seoul , 06351, Korea, Republic of
Centrum Onkologii im.prof. F. Lukaszczyka w Bydgoszczy ( Site 0273)
Bydgoszcz Kujawsko-pomorskie, 85-79, Poland
Pratia MCM Krakow ( Site 0280)
Krakow Malopolskie, 30-51, Poland
Uniwersyteckie Centrum Kliniczne ( Site 0281)
Gdansk Pomorskie, 80-21, Poland
Narodowy Instytut Onkologii - Oddzial w Gliwicach ( Site 0278)
Gliwice Slaskie, 44-10, Poland
Szpital Kliniczny im. Heliodora Swiecickiego Uniwers Medyczn ( Site 0272)
Poznan Wielkopolskie, 60-78, Poland
Cancer Care Langenhoven Drive Oncology Centre ( Site 0805)
Port Elizabeth Eastern Cape, 6045, South Africa
Sandton Oncology Medical Group PTY LTD ( Site 0802)
Johannesburg Gauteng, 2196, South Africa
Cape Town Oncology Trials Pty Ltd ( Site 0803)
Kraaifontein Western Cape, 7570, South Africa
Hospital Duran i Reinals ICO de Hospitalet ( Site 0187)
Hospitalet del Llobregat Barcelona, 08908, Spain
Hospital Universitario Marques de Valdecilla ( Site 0181)
Santander Cantabria, 39008, Spain
Complejo Hospitalario Universitario A Coruna. CHUAC ( Site 0182)
A Coruna La Coruna, 15006, Spain
Hospital Universitario Insular de Gran Canaria ( Site 0189)
Las Palmas de Gran Canaria Las Palmas, 35001, Spain
Hospital Clinic i Provincial Barcelona ( Site 0190)
Barcelona , 08036, Spain
Hospital General Universitario Gregorio Maranon ( Site 0191)
Madrid , 28009, Spain
Hospital Universitario Ramon y Cajal ( Site 0183)
Madrid , 28034, Spain
Hospital Universitario La Paz ( Site 0184)
Madrid , 28046, Spain
Hospital Universitario Carlos Haya ( Site 0186)
Malaga , 29010, Spain
Laenssjukhuset Ryhov ( Site 0215)
Jonkoping Jonkopings Lan, 551 8, Sweden
Centrallasarettet Vaxjo ( Site 0214)
Vaxjo Kronobergs Lan, 351 8, Sweden
Skanes Universitetssjukhus ( Site 0213)
Lund Skane Lan, 221 8, Sweden
Karolinska Universitetssjukhuset ( Site 0211)
Solna Stockholms Lan, 171 6, Sweden
Akademiska Sjukhuset ( Site 0218)
Uppsala Uppsala Lan, 751 8, Sweden
Norrlands Universitetssjukhus ( Site 0216)
Umea Vasterbottens Lan, 901 8, Sweden
Sahlgrenska Universitetssjukhuset ( Site 0212)
Goteborg Vastra Gotalands Lan, 413 4, Sweden
Universitaetsspital Basel ( Site 0094)
Basel Basel-Stadt, 4031, Switzerland
Kantonsspital Graubuenden ( Site 0091)
Chur Grisons, 7000, Switzerland
Kantonsspital Winterthur ( Site 0095)
Winterthur Zurich, 8401, Switzerland
Universitaetsspital Zuerich ( Site 0092)
Zuerich-Flughafen Zurich, 8058, Switzerland
Western General Hospital ( Site 0121)
Edinburgh Edinburgh, City Of, EH4 2, United Kingdom
Guys and St Thomas NHS Foundation Trust ( Site 0126)
London London, City Of, SE1 9, United Kingdom
Derriford Hospital ( Site 0129)
Plymouth , PL6 8, United Kingdom
Singleton Hospital ( Site 0131)
Swansea , SA2 8, United Kingdom

How clear is this clinincal trial information?

Study is for people with:

Melanoma

Phase:

Phase 3

Estimated Enrollment:

660

Study ID:

NCT03820986

Recruitment Status:

Active, not recruiting

Sponsor:


Merck Sharp & Dohme LLC

How clear is this clinincal trial information?

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