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)
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.
As of 03-April-2023 active participants, investigator, and sponsor personnel or delegate(s) involved in the treatment administration or clinical evaluation of the participants will be unblinded.
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.
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.
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There are 118 Locations for this study
Los Angeles California, 90025, United States
San Francisco California, 30322, United States
San Francisco California, 94115, United States
Santa Monica California, 90404, United States
Aurora Colorado, 80045, United States
New Haven Connecticut, 06510, United States
Jacksonville Florida, 32207, United States
Orange City Florida, 32763, United States
Park Ridge Illinois, 60068, United States
Peoria Illinois, 61615, United States
Fridley Minnesota, 55432, United States
Billings Montana, 59102, United States
Morristown New Jersey, 07960, United States
Paramus New Jersey, 07652, United States
Chapel Hill North Carolina, 27514, United States
Portland Oregon, 97239, United States
Fairfax Virginia, 22031, United States
Lismore Australian Capital Territory, 2480, Australia
North Sydney New South Wales, 2060, Australia
Westmead New South Wales, 2145, Australia
Wooloongabba Queensland, 4102, Australia
Box Hill Victoria, 3128, Australia
Murdoch Western Australia, 6150, Australia
Graz Steiermark, 8036, Austria
Wien , 1090, Austria
Belo Horizonte Minas Gerais, 30130, Brazil
Ijui Rio Grande Do Sul, 98700, Brazil
Passo Fundo Rio Grande Do Sul, 99010, Brazil
Porto Alegre Rio Grande Do Sul, 90610, Brazil
Rio de Janeiro , 20220, Brazil
Kelowna British Columbia, V1Y 5, Canada
North Vancouver British Columbia, V7L 2, Canada
Toronto Ontario, M4N 3, Canada
Montreal Quebec, H2W 3, Canada
Montreal Quebec, H4A 3, Canada
Temuco Araucania, 47800, Chile
Santiago Region M. De Santiago, 75009, Chile
Santiago Region M. De Santiago, 83300, Chile
Santiago Region M. De Santiago, 84203, Chile
Vina del Mar Valparaiso, 25205, Chile
Beijing Beijing, 10003, China
Fuzhou Fujian, 35001, China
Guangzhou Guangdong, 51000, China
Zhengzhou Henan, 45000, China
Nanjing Jiangsu, 21000, China
Chang Chun Jilin, 13002, China
Shanghai Shanghai, 20003, China
Tianjin Tianjin, 30006, China
Kunming Yunnan, 43003, China
Hangzhou Zhejiang, 31001, China
Hangzhou Zhejiang, 31002, China
Nice Alpes-Maritimes, 06200, France
Marseille Bouches-du-Rhone, 13385, France
Dijon Cote-d Or, 21079, France
Toulouse Haute-Garonne, 31059, France
Boulogne-Billancourt Hauts-de-Seine, 92100, France
Lille Nord, 59037, France
Rouen Seine-Maritime, 76000, France
Argenteuil Val-d Oise, 95100, France
Villejuif Val-de-Marne, 94805, France
Poitiers Vienne, 86021, France
Hannover Baden-Wurttemberg, 30625, Germany
Erlangen Bayern, 91054, Germany
Wuerzburg Bayern, 97080, Germany
Buxtehude Niedersachsen, 21614, Germany
Dresden Sachsen, 01307, Germany
Leipzig Sachsen, 04103, Germany
Kiel Schleswig-Holstein, 24105, Germany
Gera Thuringen, 07548, Germany
Afula , 18341, Israel
Beer Sheva , 84571, Israel
Haifa , 31096, Israel
Jerusalem , 91120, Israel
Petah Tikva , 49414, Israel
Ramat Gan , 52620, Israel
Tel Aviv , 64239, Israel
Zerifin , 70300, Israel
Bergamo Abruzzo, 24127, Italy
Siena Toscana, 53100, Italy
Milano , 20133, Italy
Milano , 20141, Italy
Napoli , 80131, Italy
Padova , 35128, Italy
Daegu Taegu-Kwangyokshi, 41404, Korea, Republic of
Seoul , 03080, Korea, Republic of
Seoul , 03722, Korea, Republic of
Seoul , 06351, Korea, Republic of
Bydgoszcz Kujawsko-pomorskie, 85-79, Poland
Krakow Malopolskie, 30-51, Poland
Gdansk Pomorskie, 80-21, Poland
Gliwice Slaskie, 44-10, Poland
Poznan Wielkopolskie, 60-78, Poland
Port Elizabeth Eastern Cape, 6045, South Africa
Johannesburg Gauteng, 2196, South Africa
Kraaifontein Western Cape, 7570, South Africa
Hospitalet del Llobregat Barcelona, 08908, Spain
Santander Cantabria, 39008, Spain
A Coruna La Coruna, 15006, Spain
Las Palmas de Gran Canaria Las Palmas, 35001, Spain
Barcelona , 08036, Spain
Madrid , 28009, Spain
Madrid , 28034, Spain
Madrid , 28046, Spain
Malaga , 29010, Spain
Jonkoping Jonkopings Lan, 551 8, Sweden
Vaxjo Kronobergs Lan, 351 8, Sweden
Lund Skane Lan, 221 8, Sweden
Solna Stockholms Lan, 171 6, Sweden
Uppsala Uppsala Lan, 751 8, Sweden
Umea Vasterbottens Lan, 901 8, Sweden
Goteborg Vastra Gotalands Lan, 413 4, Sweden
Basel Basel-Stadt, 4031, Switzerland
Chur Grisons, 7000, Switzerland
Winterthur Zurich, 8401, Switzerland
Zuerich-Flughafen Zurich, 8058, Switzerland
Edinburgh Edinburgh, City Of, EH4 2, United Kingdom
London London, City Of, SE1 9, United Kingdom
Plymouth , PL6 8, United Kingdom
Swansea , SA2 8, United Kingdom
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