Podstudie 03A: Studie imunitních a cílených kombinovaných terapií u účastníků s první linií (1L) renálním karcinomem (MK-3475-03A)
Studie 1b/2 fáze imunitní a cílené kombinované terapie u účastníků s RCC (U03): Podstudie 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.
Přehled studie
Postavení
Postavení
Podmínky
Podmínky
Intervence / Léčba
Intervence / Léčba
Typ studie
Typ studie
Zápis (Aktuální)
Zápis
Fáze
Fáze
- Fáze 2
- Fáze 1
Kontakty a umístění
Studijní místa
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New South Wales
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Blacktown, New South Wales, Austrálie, 2148
- Blacktown Hospital ( Site 1601)
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Kogarah, New South Wales, Austrálie, 2217
- St George Hospital ( Site 1602)
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Queensland
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Herston, Queensland, Austrálie, 4029
- Royal Brisbane and Women's Hospital ( Site 1603)
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Victoria
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Heidelberg, Victoria, Austrálie, 3084
- Austin Health ( Site 1600)
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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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Ain
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Vandœuvre-lès-Nancy, Ain, Francie, 54519
- Institut De Cancerologie De Lorraine ( Site 1204)
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Bas-Rhin
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Strasbourg, Bas-Rhin, Francie, 67098
- C.H.U. de Strasbourg Hopital de Hautepierre ( Site 1203)
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Haute-Garonne
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Toulouse, Haute-Garonne, Francie, 31059
- Institut Claudius Regaud ( Site 1200)
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Île-de-France Region
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Villejuif, Île-de-France Region, Francie, 94800
- Gustave Roussy ( Site 1202)
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North Holland
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Amsterdam, North Holland, Holandsko, 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, Holandsko, 3015 GD
- Erasmus Medisch Centrum ( Site 2401)
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Haifa, Izrael, 3525408
- Rambam MC ( Site 1500)
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Jerusalem, Izrael, 9112001
- Hadassah Medical Center-Oncology ( Site 1504)
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Petah Tikva, Izrael, 4941492
- Rabin Medical Center ( Site 1502)
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Ramat Gan, Izrael, 52621
- Sheba Medical Center - Oncology Division ( Site 1501)
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Tel Aviv, Izrael, 6423906
- Sourasky Medical Center ( Site 1503)
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Seoul, Jižní Korea, 03722
- Severance Hospital ( Site 1802)
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Seoul, Jižní Korea, 06351
- Samsung Medical Center ( Site 1801)
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Seoul
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Songpagu, Seoul, Jižní Korea, 05505
- Asan Medical Center ( Site 1800)
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Ontario
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Toronto, Ontario, Kanada, M5G 1Z5
- Princess Margaret Cancer Centre ( Site 1101)
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Quebec
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Montreal, Quebec, Kanada, H3T 1E2
- Jewish General Hospital ( Site 1100)
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Bogota D.C.
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Bogotá, Bogota D.C., Kolumbie, 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, Kolumbie, 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, Kolumbie, 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, Kolumbie, 760032
- Fundación Valle del Lili ( Site 1901)
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Pest County
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Budapest, Pest County, Maďarsko, 1122
- Országos Onkológiai Intézet-Urogenitális Tumorok és Klinikai Farmakológiai Osztály ( Site 2301)
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Auckland, Nový Zéland, 1023
- Auckland City Hospital ( Site 1700)
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Kuyavian-Pomeranian Voivodeship
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Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Polsko, 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, Polsko, 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, Polsko, 80-952
- Uniwersyteckie Centrum Kliniczne-Early Clinical Trials Unit ( Site 2202)
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Manchester, Spojené království, M20 4BX
- The Christie NHS Foundation Trust ( Site 1400)
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England
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Southampton, England, Spojené království, SO16 6YD
- Southampton General Hospital ( Site 1403)
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Glasgow City
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Glasgow, Glasgow City, Spojené království, G12 0YN
- The Beatson West of Scotland Cancer Centre ( Site 1405)
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Lancashire
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Preston, Lancashire, Spojené království, PR2 9HT
- Royal Preston Hospital ( Site 1406)
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Leicestershire
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Leicester, Leicestershire, Spojené království, LE1 5WW
- Leicester Royal Infirmary ( Site 1408)
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London, City of
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London, London, City of, Spojené království, EC1A 7BE
- Barts Health NHS Trust ( Site 1401)
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Midlothian
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Edinburgh, Midlothian, Spojené království, EH4 2XU
- Western General Hospital ( Site 1402)
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Wales
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Cardiff, Wales, Spojené království, CF14 2TL
- Velindre Cancer Centre Hospital ( Site 1407)
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California
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San Francisco, California, Spojené státy, 94158
- University of California at San Francisco ( Site 1008)
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Connecticut
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New Haven, Connecticut, Spojené státy, 06510
- Yale-New Haven Hospital-Yale Cancer Center ( Site 1011)
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Illinois
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Chicago, Illinois, Spojené státy, 60637
- University of Chicago ( Site 1013)
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Iowa
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Iowa City, Iowa, Spojené státy, 52242
- University of Iowa ( Site 1012)
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Michigan
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Detroit, Michigan, Spojené státy, 48202
- Henry Ford Health System ( Site 1014)
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New York
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New York, New York, Spojené státy, 10016
- Laura and Isaac Perlmutter Cancer Center ( Site 1016)
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New York, New York, Spojené státy, 10065
- Memorial Sloan Kettering Cancer Center ( Site 1002)
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North Carolina
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Durham, North Carolina, Spojené státy, 27710
- Duke Cancer Institute ( Site 1015)
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Pennsylvania
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Pittsburgh, Pennsylvania, Spojené státy, 15232
- UPMC Cancer Center/Hillman Cancer Center ( Site 1017)
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Texas
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Dallas, Texas, Spojené státy, 75390
- UTSW Medical Center ( Site 1003)
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Madrid, Španělsko, 28034
- Hospital Universitario Ramon y Cajal ( Site 1301)
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Catalonia
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Barcelona, Catalonia, Španělsko, 08035
- Hospital Universitari Vall d Hebron ( Site 1300)
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Kritéria účasti
Kritéria způsobilosti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
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
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Žádné (otevřený štítek)
Počet zbraní
Zbraně a zásahy
Skupina účastníků / ArmSkupina účastníků / Arm |
Intervence / LéčbaIntervence / Léčba |
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Experimentální: 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
Ostatní jména:
Administered via IV infusion at a dose of 400 mg/25 mg Q6W
Ostatní jména:
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Experimentální: 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
Ostatní jména:
Administered via IV infusion at a dose of 800 mg/200 mg Q3W
Ostatní jména:
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Experimentální: 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
Ostatní jména:
Administered via IV infusion at a dose of 400 mg Q6W
Ostatní jména:
Administered via oral tablet at a dose of 120 mg QD
Ostatní jména:
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Experimentální: 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
Ostatní jména:
Administered via IV infusion at a dose of 400 mg Q6W
Ostatní jména:
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Experimentální: 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
Ostatní jména:
Administered via IV infusion at a dose of 200 mg/200 mg Q6W
Ostatní jména:
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Co je měření studie?
Primární výstupní opatření
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Safety Lead-in Phase: Number of participants who experience one or more dose-limiting toxicities (DLTs)
Časové okno: 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 safety lead-in phase will be presented. |
Up to ~21 days
|
|
Safety Lead-in Phase: Number of participants who experience one or more adverse events (AEs)
Časové okno: Up to ~21 days
|
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
|
|
Safety Lead-in Phase: Number of participants who discontinue study treatment due to an AE
Časové okno: Up to ~21 days
|
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
|
|
Efficacy Phase: Number of participants who experience one or more DLTs
Časové okno: 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
|
|
Efficacy Phase: Number of participants who experience one or more AEs
Časové okno: 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
|
|
Efficacy Phase: Number of participants who discontinue study treatment due to an AE
Časové okno: 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)
Časové okno: 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
|
Sekundární výstupní opatření
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Efficacy Phase: Duration of response (DOR)
Časové okno: 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
|
|
Efficacy Phase: Progression-free survival (PFS)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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
|
Spolupracovníci a vyšetřovatelé
Sponzor
Sponzor
Vyšetřovatelé
Vyšetřovatelé
- Ředitel studie: Medical Director, Merck Sharp & Dohme LLC
Publikace a užitečné odkazy
Užitečné odkazy
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Začátek studia
Primární dokončení (Aktuální)
Primární dokončení
Dokončení studie (Aktuální)
Dokončení studie
Termíny zápisu do studia
První předloženo
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
První zveřejněno
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Poslední zveřejněná aktualizace
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
- Urogenitální onemocnění
- Urogenitální novotvary
- Novotvary podle místa
- Novotvary
- Mužská urogenitální onemocnění
- Onemocnění ledvin
- Urologická onemocnění
- Ženské urogenitální onemocnění
- Ženské urogenitální onemocnění a těhotenské komplikace
- Novotvary podle histologického typu
- Novotvary, žlázové a epiteliální
- Adenokarcinom
- Urologické novotvary
- Karcinom
- Novotvary ledvin
- Karcinom, renální buňka
- Parkinsonova choroba 4, autozomálně dominantní Lewy Body
- Pembrolizumab
- Belzutifan
- Lenvatinib
Další identifikační čísla studie
Další identifikační čísla studie
- 3475-03A
- MK-3475-03A (Jiný identifikátor: MSD)
- 2019-003609-84 (Číslo EudraCT)
- 2023-506838-68-00 (Identifikátor registru: EU CT)
- U1111-1294-4527 (Identifikátor registru: UTN)
- 2023 (Grant/smlouva NIH USA)
- 2019 (Grant/smlouva NIH USA)
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
Popis plánu IPD
https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Studuje produkt zařízení regulovaný americkým úřadem FDA
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