サブスタディ 03A: 第一選択 (1L) 腎細胞癌 (MK-3475-03A) の参加者における免疫および標的併用療法の研究
RCCの参加者における免疫および標的併用療法の第1b / 2相研究（U03）：サブスタディ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.
調査の概要
状態
条件
研究の種類
入学 (実際)
段階
- フェーズ2
- フェーズ 1
連絡先と場所
研究場所
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California
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San Francisco、California、アメリカ、94158
- University of California at San Francisco ( Site 1008)
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Connecticut
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New Haven、Connecticut、アメリカ、06510
- Yale-New Haven Hospital-Yale Cancer Center ( Site 1011)
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Illinois
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Chicago、Illinois、アメリカ、60637
- University of Chicago ( Site 1013)
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Iowa
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Iowa City、Iowa、アメリカ、52242
- University of Iowa ( Site 1012)
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Michigan
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Detroit、Michigan、アメリカ、48202
- Henry Ford Health System ( Site 1014)
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New York
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New York、New York、アメリカ、10016
- Laura and Isaac Perlmutter Cancer Center ( Site 1016)
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New York、New York、アメリカ、10065
- Memorial Sloan Kettering Cancer Center ( Site 1002)
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North Carolina
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Durham、North Carolina、アメリカ、27710
- Duke Cancer Institute ( Site 1015)
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Pennsylvania
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Pittsburgh、Pennsylvania、アメリカ、15232
- UPMC Cancer Center/Hillman Cancer Center ( Site 1017)
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Texas
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Dallas、Texas、アメリカ、75390
- UTSW Medical Center ( Site 1003)
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Manchester、イギリス、M20 4BX
- The Christie NHS Foundation Trust ( Site 1400)
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England
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Southampton、England、イギリス、SO16 6YD
- Southampton General Hospital ( Site 1403)
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Glasgow City
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Glasgow、Glasgow City、イギリス、G12 0YN
- The Beatson West of Scotland Cancer Centre ( Site 1405)
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Lancashire
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Preston、Lancashire、イギリス、PR2 9HT
- Royal Preston Hospital ( Site 1406)
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Leicestershire
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Leicester、Leicestershire、イギリス、LE1 5WW
- Leicester Royal Infirmary ( Site 1408)
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London, City of
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London、London, City of、イギリス、EC1A 7BE
- Barts Health NHS Trust ( Site 1401)
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Midlothian
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Edinburgh、Midlothian、イギリス、EH4 2XU
- Western General Hospital ( Site 1402)
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Wales
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Cardiff、Wales、イギリス、CF14 2TL
- Velindre Cancer Centre Hospital ( Site 1407)
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Haifa、イスラエル、3525408
- Rambam MC ( Site 1500)
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Jerusalem、イスラエル、9112001
- Hadassah Medical Center-Oncology ( Site 1504)
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Petah Tikva、イスラエル、4941492
- Rabin Medical Center ( Site 1502)
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Ramat Gan、イスラエル、52621
- Sheba Medical Center - Oncology Division ( Site 1501)
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Tel Aviv、イスラエル、6423906
- Sourasky Medical Center ( Site 1503)
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North Holland
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Amsterdam、North Holland、オランダ、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、オランダ、3015 GD
- Erasmus Medisch Centrum ( Site 2401)
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New South Wales
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Blacktown、New South Wales、オーストラリア、2148
- Blacktown Hospital ( Site 1601)
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Kogarah、New South Wales、オーストラリア、2217
- St George Hospital ( Site 1602)
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Queensland
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Herston、Queensland、オーストラリア、4029
- Royal Brisbane and Women's Hospital ( Site 1603)
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Victoria
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Heidelberg、Victoria、オーストラリア、3084
- Austin Health ( Site 1600)
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Ontario
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Toronto、Ontario、カナダ、M5G 1Z5
- Princess Margaret Cancer Centre ( Site 1101)
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Quebec
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Montreal、Quebec、カナダ、H3T 1E2
- Jewish General Hospital ( Site 1100)
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Bogota D.C.
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Bogotá、Bogota D.C.、コロンビア、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、コロンビア、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、コロンビア、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、コロンビア、760032
- Fundación Valle del Lili ( Site 1901)
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Madrid、スペイン、28034
- Hospital Universitario Ramon y Cajal ( Site 1301)
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Catalonia
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Barcelona、Catalonia、スペイン、08035
- Hospital Universitari Vall d Hebron ( Site 1300)
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Araucania
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Temuco、Araucania、チリ、4800827
- James Lind Centro de Investigacion del Cancer ( Site 2108)
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Temuco、Araucania、チリ、4810148
- CIDO SpA-Oncology ( Site 2106)
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Region M. de Santiago
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Santiago、Region M. de Santiago、チリ、7500921
- FALP-UIDO ( Site 2100)
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Santiago、Region M. de Santiago、チリ、8420383
- Bradfordhill-Clinical Area ( Site 2101)
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Santiago、Region M. de Santiago、チリ、7500994
- Oncovida ( Site 2107)
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Valparaiso
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Viña del Mar、Valparaiso、チリ、2520598
- ONCOCENTRO APYS-ACEREY ( Site 2103)
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Auckland、ニュージーランド、1023
- Auckland City Hospital ( Site 1700)
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Pest County
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Budapest、Pest County、ハンガリー、1122
- Országos Onkológiai Intézet-Urogenitális Tumorok és Klinikai Farmakológiai Osztály ( Site 2301)
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Ain
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Vandœuvre-lès-Nancy、Ain、フランス、54519
- Institut De Cancerologie De Lorraine ( Site 1204)
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Bas-Rhin
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Strasbourg、Bas-Rhin、フランス、67098
- C.H.U. de Strasbourg Hopital de Hautepierre ( Site 1203)
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Haute-Garonne
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Toulouse、Haute-Garonne、フランス、31059
- Institut Claudius Regaud ( Site 1200)
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Île-de-France Region
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Villejuif、Île-de-France Region、フランス、94800
- Gustave Roussy ( Site 1202)
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Kuyavian-Pomeranian Voivodeship
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Bydgoszcz、Kuyavian-Pomeranian Voivodeship、ポーランド、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、ポーランド、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、ポーランド、80-952
- Uniwersyteckie Centrum Kliniczne-Early Clinical Trials Unit ( Site 2202)
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Seoul、韓国、03722
- Severance Hospital ( Site 1802)
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Seoul、韓国、06351
- Samsung Medical Center ( Site 1801)
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Seoul
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Songpagu、Seoul、韓国、05505
- Asan Medical Center ( Site 1800)
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：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
他の名前：
Administered via IV infusion at a dose of 400 mg/25 mg Q6W
他の名前：
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実験的：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
他の名前：
Administered via IV infusion at a dose of 800 mg/200 mg Q3W
他の名前：
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実験的：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
他の名前：
Administered via IV infusion at a dose of 400 mg Q6W
他の名前：
Administered via oral tablet at a dose of 120 mg QD
他の名前：
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実験的：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
他の名前：
Administered via IV infusion at a dose of 400 mg Q6W
他の名前：
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実験的：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
他の名前：
Administered via IV infusion at a dose of 200 mg/200 mg Q6W
他の名前：
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Safety Lead-in Phase: Number of participants who experience one or more dose-limiting toxicities (DLTs)
時間枠：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)
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
|
|
Efficacy Phase: Objective response rate (ORR)
時間枠：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
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Efficacy Phase: Duration of response (DOR)
時間枠：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)
時間枠：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)
時間枠：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)
時間枠：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
|
協力者と研究者
スポンサー
捜査官
- スタディディレクター：Medical Director、Merck Sharp & Dohme LLC
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- 3475-03A
- MK-3475-03A (その他の識別子：MSD)
- 2019-003609-84 (EudraCT番号)
- 2023-506838-68-00 (レジストリ識別子：EU CT)
- U1111-1294-4527 (レジストリ識別子：UTN)
- 2023 (米国 NIH グラント/契約)
- 2019 (米国 NIH グラント/契約)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。