Subestudo 03A: Um estudo de terapias combinadas imunológicas e direcionadas em participantes com carcinoma de células renais de primeira linha (1L) (MK-3475-03A)
Um estudo de Fase 1b/2 de terapias imunológicas e de combinação direcionada em participantes com RCC (U03): Subestudo 03A
Substudy 03A is part of a larger research study that is testing experimental treatments for renal cell carcinoma (RCC). The larger study is the umbrella study (U03).
The goal of substudy 03A is to evaluate the safety and efficacy of experimental combinations of investigational agents in participants with advanced first line (1L) clear cell renal cell carcinoma (ccRCC).
This substudy will have two phases: a safety lead-in phase and an efficacy phase. The safety lead-in phase will be used to demonstrate a tolerable safety profile for the combination of investigational agents. There will be no hypothesis testing in this study.
Visão geral do estudo
Status
Condições
Tipo de estudo
Inscrição (Real)
Estágio
- Fase 2
- Fase 1
Contactos e Locais
Locais de estudo
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New South Wales
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Blacktown, New South Wales, Austrália, 2148
- Blacktown Hospital ( Site 1601)
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Kogarah, New South Wales, Austrália, 2217
- St George Hospital ( Site 1602)
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Queensland
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Herston, Queensland, Austrália, 4029
- Royal Brisbane and Women's Hospital ( Site 1603)
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Victoria
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Heidelberg, Victoria, Austrália, 3084
- Austin Health ( Site 1600)
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Ontario
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Toronto, Ontario, Canadá, M5G 1Z5
- Princess Margaret Cancer Centre ( Site 1101)
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Quebec
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Montreal, Quebec, Canadá, H3T 1E2
- Jewish General Hospital ( Site 1100)
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Araucania
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Temuco, Araucania, Chile, 4800827
- James Lind Centro de Investigacion del Cancer ( Site 2108)
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Temuco, Araucania, Chile, 4810148
- CIDO SpA-Oncology ( Site 2106)
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Region M. de Santiago
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Santiago, Region M. de Santiago, Chile, 7500921
- FALP-UIDO ( Site 2100)
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Santiago, Region M. de Santiago, Chile, 8420383
- Bradfordhill-Clinical Area ( Site 2101)
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Santiago, Region M. de Santiago, Chile, 7500994
- Oncovida ( Site 2107)
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Valparaiso
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Viña del Mar, Valparaiso, Chile, 2520598
- ONCOCENTRO APYS-ACEREY ( Site 2103)
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Bogota D.C.
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Bogotá, Bogota D.C., Colômbia, 111321
- Clinica Colsanitas S.A, Sede Clínica Universitaria Colombia-Center Investigator ( Site 1900)
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Cesar Department
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Valledupar, Cesar Department, Colômbia, 200001
- Sociedad De Oncologia Y Hematologia Del Cesar-Oncology ( Site 1905)
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Departamento de Córdoba
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Montería, Departamento de Córdoba, Colômbia, 230002
- Instituto Médico de Alta Tecnologia S.A.S ( Site 1904)
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Valle del Cauca Department
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Cali, Valle del Cauca Department, Colômbia, 760032
- Fundación Valle del Lili ( Site 1901)
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Seoul, Coréia do Sul, 03722
- Severance Hospital ( Site 1802)
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Seoul, Coréia do Sul, 06351
- Samsung Medical Center ( Site 1801)
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Seoul
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Songpagu, Seoul, Coréia do Sul, 05505
- Asan Medical Center ( Site 1800)
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Madrid, Espanha, 28034
- Hospital Universitario Ramon y Cajal ( Site 1301)
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Catalonia
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Barcelona, Catalonia, Espanha, 08035
- Hospital Universitari Vall d Hebron ( Site 1300)
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California
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San Francisco, California, Estados Unidos, 94158
- University of California at San Francisco ( Site 1008)
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Connecticut
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New Haven, Connecticut, Estados Unidos, 06510
- Yale-New Haven Hospital-Yale Cancer Center ( Site 1011)
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Illinois
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Chicago, Illinois, Estados Unidos, 60637
- University of Chicago ( Site 1013)
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Iowa
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Iowa City, Iowa, Estados Unidos, 52242
- University of Iowa ( Site 1012)
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Michigan
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Detroit, Michigan, Estados Unidos, 48202
- Henry Ford Health System ( Site 1014)
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New York
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New York, New York, Estados Unidos, 10016
- Laura and Isaac Perlmutter Cancer Center ( Site 1016)
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New York, New York, Estados Unidos, 10065
- Memorial Sloan Kettering Cancer Center ( Site 1002)
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North Carolina
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Durham, North Carolina, Estados Unidos, 27710
- Duke Cancer Institute ( Site 1015)
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Pennsylvania
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Pittsburgh, Pennsylvania, Estados Unidos, 15232
- UPMC Cancer Center/Hillman Cancer Center ( Site 1017)
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Texas
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Dallas, Texas, Estados Unidos, 75390
- UTSW Medical Center ( Site 1003)
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Ain
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Vandœuvre-lès-Nancy, Ain, França, 54519
- Institut De Cancerologie De Lorraine ( Site 1204)
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Bas-Rhin
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Strasbourg, Bas-Rhin, França, 67098
- C.H.U. de Strasbourg Hopital de Hautepierre ( Site 1203)
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Haute-Garonne
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Toulouse, Haute-Garonne, França, 31059
- Institut Claudius Regaud ( Site 1200)
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Île-de-France Region
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Villejuif, Île-de-France Region, França, 94800
- Gustave Roussy ( Site 1202)
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North Holland
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Amsterdam, North Holland, Holanda, 1066 CX
- Nederlands Kanker Instituut - Antoni van Leeuwenhoek (NKI-AVL)-medical oncology ( Site 2402)
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South Holland
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Rotterdam, South Holland, Holanda, 3015 GD
- Erasmus Medisch Centrum ( Site 2401)
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Pest County
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Budapest, Pest County, Hungria, 1122
- Országos Onkológiai Intézet-Urogenitális Tumorok és Klinikai Farmakológiai Osztály ( Site 2301)
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Haifa, Israel, 3525408
- Rambam MC ( Site 1500)
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Jerusalem, Israel, 9112001
- Hadassah Medical Center-Oncology ( Site 1504)
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Petah Tikva, Israel, 4941492
- Rabin Medical Center ( Site 1502)
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Ramat Gan, Israel, 52621
- Sheba Medical Center - Oncology Division ( Site 1501)
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Tel Aviv, Israel, 6423906
- Sourasky Medical Center ( Site 1503)
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Auckland, Nova Zelândia, 1023
- Auckland City Hospital ( Site 1700)
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Kuyavian-Pomeranian Voivodeship
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Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Polônia, 85-796
- Centrum Onkologii im. Prof. Franciszka Lukaszczyka-Ambulatorium Chemioterapii ( Site 2201)
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Masovian Voivodeship
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Warsaw, Masovian Voivodeship, Polônia, 02-781
- Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Oddzial Badan Wczesnych Faz ( Site 2200)
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Pomeranian Voivodeship
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Gdansk, Pomeranian Voivodeship, Polônia, 80-952
- Uniwersyteckie Centrum Kliniczne-Early Clinical Trials Unit ( Site 2202)
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Manchester, Reino Unido, M20 4BX
- The Christie NHS Foundation Trust ( Site 1400)
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England
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Southampton, England, Reino Unido, SO16 6YD
- Southampton General Hospital ( Site 1403)
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Glasgow City
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Glasgow, Glasgow City, Reino Unido, G12 0YN
- The Beatson West of Scotland Cancer Centre ( Site 1405)
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Lancashire
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Preston, Lancashire, Reino Unido, PR2 9HT
- Royal Preston Hospital ( Site 1406)
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Leicestershire
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Leicester, Leicestershire, Reino Unido, LE1 5WW
- Leicester Royal Infirmary ( Site 1408)
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London, City of
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London, London, City of, Reino Unido, EC1A 7BE
- Barts Health NHS Trust ( Site 1401)
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Midlothian
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Edinburgh, Midlothian, Reino Unido, EH4 2XU
- Western General Hospital ( Site 1402)
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Wales
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Cardiff, Wales, Reino Unido, CF14 2TL
- Velindre Cancer Centre Hospital ( Site 1407)
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion Criteria:
- Has a histologically confirmed diagnosis of locally advanced/metastatic ccRCC
- Has received no prior systemic therapy for advanced RCC; prior neoadjuvant/adjuvant therapy for RCC is acceptable if completed ≥12 months before randomization/allocation.
- Is able to swallow oral medication
- Has adequate organ function
- Participants receiving bone resorptive therapy must have therapy initiated at least 2 weeks before randomization/allocation
- Has resolution of toxic effects of the most recent prior therapy to ≤Grade 1
- Has adequately controlled blood pressure (BP ≤150/90 mm Hg) with no change in hypertensive medications within 1 week before randomization/allocation
- Male participants are abstinent from heterosexual intercourse or agree to use contraception during treatment with and for at least 7 days after the last dose of lenvatinib and /or belzutifan; 7 days after lenvatinib and/or belzutifan is stopped, if the participant is only receiving pembrolizumab, pembrolizumab/quavonlimab, favezelimab/pembrolizumab or a combination of the aforementioned drugs, no contraception is needed
- Female participants must not be pregnant and not be a woman of childbearing potential (WOCBP) or is a WOCBP abstinent from heterosexual intercourse or using contraception during the intervention period and for at least 120 days after the last dose of pembrolizumab, pembrolizumab/quavonlimab, favezelimab/pembrolizumab for 30 days after the last dose of lenvatinib or belzutifan, whichever occurs last and must abstain from breastfeeding during the study intervention period and for at least 120 days after study intervention
Exclusion Criteria:
- Has urine protein ≥1 g/24 hours and has any of the following: (a) a pulse oximeter reading <92% at rest, or (b) requires intermittent supplemental oxygen, or (c) requires chronic supplemental oxygen (d) active hemoptysis within 3 weeks prior to the first dose of study intervention
- Has clinically significant cardiovascular disease within 12 months from the first dose of study intervention administration
- Has had major surgery within 3 weeks before first dose of study interventions
- Has a history of lung disease
- Has a history of inflammatory bowel disease
- Has preexisting gastrointestinal (GI) or non-GI fistula
- Has malabsorption due to prior GI surgery or disease
- Has received prior radiotherapy within 2 weeks of start of study intervention
- Has received a live or live attenuated vaccine within 30 days before the first dose of study drug; killed vaccines are allowed
- Has received more than 4 previous systemic anticancer treatment regimens
- Has a diagnosis of immunodeficiency or is receiving any form of immunosuppressive therapy within 7 days prior to the first dose of study intervention
- Has known additional malignancy that is progressing or has required active treatment within the past 3 years
- Has known central nervous system (CNS) metastases and/or carcinomatous meningitis
- Has an active autoimmune disease that has required systemic treatment in the past 2 years; replacement therapy is not considered a form of systemic treatment and is allowed
- Has an active infection requiring systemic therapy
- Has a known history of human immunodeficiency virus (HIV) infection
- Has a known history of Hepatitis B
- Has had an allogenic tissue/solid organ transplant
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
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Experimental: Coformulation Pembrolizumab/Quavonlimab + Lenvatinib
Participants will receive pembrolizumab/quavonlimab (coformulation of pembrolizumab 400 mg and quavonlimab 25 mg) PLUS lenvatinib 20 mg. Pembrolizumab/quavonlimab will be administered intravenously (IV) once every 6 weeks (Q6W) for up to 17 administrations (up to ~2 years). Lenvatinib will be administered orally once-daily (QD) until progressive disease or discontinuation. |
Administered via oral capsule at a dose of 20 mg QD
Outros nomes:
Administered via IV infusion at a dose of 400 mg/25 mg Q6W
Outros nomes:
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Experimental: Coformulation Favezelimab/Pembrolizumab+ Lenvatinib
Participants will receive favezelimab/pembrolizumab (coformulation of favezelimab 800 mg and pembrolizumab 200 mg) PLUS lenvatinib 20 mg. Favezelimab/Pembrolizumab will be administered IV once every 3 weeks (Q3W) for up to 35 administrations (up to ~2 years). Lenvatinib will be administered orally QD until progressive disease or discontinuation. |
Administered via oral capsule at a dose of 20 mg QD
Outros nomes:
Administered via IV infusion at a dose of 800 mg/200 mg Q3W
Outros nomes:
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Experimental: Pembrolizumab + Belzutifan + Lenvatinib
Participants will receive pembrolizumab 400 mg PLUS belzutifan 120 mg PLUS lenvatinib 20 mg. Pembrolizumab will be administered IV Q6W for up to 17 administrations (up to ~2 years). Both belzutifan and lenvatinib will be administered orally QD until progressive disease or discontinuation. |
Administered via oral capsule at a dose of 20 mg QD
Outros nomes:
Administered via IV infusion at a dose of 400 mg Q6W
Outros nomes:
Administered via oral tablet at a dose of 120 mg QD
Outros nomes:
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Experimental: Pembrolizumab + Lenvatinib
Participants will receive pembrolizumab 400 mg PLUS lenvatinib 20 mg. Pembrolizumab will be administered IV Q6W for up to 17 administrations (up to ~ 2 years). Lenvatinib will be administered orally QD until progressive disease or discontinuation. |
Administered via oral capsule at a dose of 20 mg QD
Outros nomes:
Administered via IV infusion at a dose of 400 mg Q6W
Outros nomes:
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Experimental: Coformulation Vibostolimab/Pembrolizumab+Belzutifan
Participants will receive vibostolimab/pembrolizumab (coformulation of 200 mg vibostolimab and pembrolizumab 200 mg). Vibostolimab/pembrolizumab will be administered IV once every 3 weeks (Q3W) for up to 35 administrations (up to ~2 years). Belzutifan will be administered orally QD until progressive disease or discontinuation. |
Administered via oral tablet at a dose of 120 mg QD
Outros nomes:
Administered via IV infusion at a dose of 200 mg/200 mg Q6W
Outros nomes:
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Safety Lead-in Phase: Number of participants who experience one or more dose-limiting toxicities (DLTs)
Prazo: Up to ~21 days
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DLTs are defined as one or more of the following toxicities: (1) grade (gr) 4 nonhematologic toxicity (2) gr 4 hematologic toxicity lasting >7 days OR gr 4 platelet count decreased of any duration OR gr 3 platelet count decreased if associated with bleeding (3) gr 3 nonhematologic toxicity except gr 3 fatigue (lasting ≤3 days), diarrhea, nausea, vomiting or rash without standard of care (4) gr 3 or 4 nonhematologic abnormality if medical intervention is required or if it leads to hospitalization or persists for >1 week (5) gr 3 or 4 febrile neutropenia (6) gr 3 or 4 alanine aminotransferase, aspartate aminotransferase and/or bilirubin laboratory value (7) treatment related adverse event (AE) causing study intervention discontinuation during the first 21 days (8) treatment related AE causing intervention administration delay for >14 days during the first 21 days (9) gr 5 toxicity. The number of participants who experience one or more DLTs in the safety lead-in phase will be presented. |
Up to ~21 days
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Safety Lead-in Phase: Number of participants who experience one or more adverse events (AEs)
Prazo: Up to ~21 days
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An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience one or more AEs in the safety lead-in phase will be presented. |
Up to ~21 days
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Safety Lead-in Phase: Number of participants who discontinue study treatment due to an AE
Prazo: Up to ~21 days
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An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinue study treatment due to an AE in the safety lead-in phase will be presented. |
Up to ~21 days
|
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Efficacy Phase: Number of participants who experience one or more DLTs
Prazo: Up to ~21 days
|
DLTs are defined as one or more of the following toxicities: (1) grade (gr) 4 nonhematologic toxicity (2) gr 4 hematologic toxicity lasting >7 days OR gr 4 platelet count decreased of any duration OR gr 3 platelet count decreased if associated with bleeding (3) gr 3 nonhematologic toxicity except gr 3 fatigue (lasting ≤3 days), diarrhea, nausea, vomiting or rash without standard of care (4) gr 3 or 4 nonhematologic abnormality if medical intervention is required or if it leads to hospitalization or persists for >1 week (5) gr 3 or 4 febrile neutropenia (6) gr 3 or 4 alanine aminotransferase, aspartate aminotransferase and/or bilirubin laboratory value (7) treatment related adverse event (AE) causing study intervention discontinuation during the first 21 days (8) treatment related AE causing intervention administration delay for >14 days during the first 21 days (9) gr 5 toxicity. The number of participants who experience one or more DLTs in the efficacy phase will be presented. |
Up to ~21 days
|
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Efficacy Phase: Number of participants who experience one or more AEs
Prazo: Up to ~43 months
|
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience one or more AEs in the efficacy phase will be presented. |
Up to ~43 months
|
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Efficacy Phase: Number of participants who discontinue study treatment due to an AE
Prazo: Up to ~43 months
|
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinue study treatment due to an AE in the efficacy phase will be presented. |
Up to ~43 months
|
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Efficacy Phase: Objective response rate (ORR)
Prazo: Up to ~43 months
|
ORR is defined as the percentage of participants in the analysis population who have a complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters). Responses are according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR). |
Up to ~43 months
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Efficacy Phase: Duration of response (DOR)
Prazo: Up to ~43 months
|
For participants in the analysis population who demonstrate a confirmed CR (disappearance of all target lesions) or confirmed PR (at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters), DOR is defined as the time from first documented evidence of CR or PR until progressive disease or death due to any cause, whichever occurs first. Responses are according to RECIST 1.1 by BICR. |
Up to ~43 months
|
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Efficacy Phase: Progression-free survival (PFS)
Prazo: Up to ~43 months
|
PFS is defined as the time from randomization to the first documented progressive disease or death due to any cause, whichever occurs first. Responses are according to RECIST 1.1 by BICR. |
Up to ~43 months
|
|
Efficacy Phase: Overall survival (OS)
Prazo: Up to ~43 months
|
OS is defined as the time from randomization to death due to any cause. |
Up to ~43 months
|
|
Efficacy Phase: Clinical benefit rate (CBR)
Prazo: Up to ~43 months
|
CBR is defined as the percentage of participants who have achieved CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters) or stable disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease) of ≥6 months. Responses are according to RECIST 1.1 by BICR. |
Up to ~43 months
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Diretor de estudo: Medical Director, Merck Sharp & Dohme LLC
Publicações e links úteis
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Real)
Conclusão do estudo (Real)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Doenças urogenitais
- Neoplasias urogenitais
- Neoplasias por local
- Neoplasias
- Doenças Urogenitais Masculinas
- Doenças renais
- Doenças Urológicas
- Doenças Urogenitais Femininas
- Doenças urogenitais femininas e complicações na gravidez
- Neoplasias por Tipo Histológico
- Neoplasias Glandulares e Epiteliais
- Adenocarcinoma
- Neoplasias Urológicas
- Carcinoma
- Neoplasias Renais
- Carcinoma de Células Renais
- Doença de Parkinson 4, Corpo Autossômico Dominante de Lewy
- Pembrolizumab
- Belzutifan
- Lenvatinib
Outros números de identificação do estudo
- 3475-03A
- MK-3475-03A (Outro identificador: MSD)
- 2019-003609-84 (Número EudraCT)
- 2023-506838-68-00 (Identificador de registro: EU CT)
- U1111-1294-4527 (Identificador de registro: UTN)
- 2023 (Concessão/Contrato do NIH dos EUA)
- 2019 (Concessão/Contrato do NIH dos EUA)
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
Descrição do plano IPD
https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
Informações sobre medicamentos e dispositivos, documentos de estudo
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