Substudy 03A: A Study of Immune and Targeted Combination Therapies in Participants With First Line (1L) Renal Cell Carcinoma (MK-3475-03A)
Carcinoma, Renal Cell
About this trial
This is an interventional treatment trial for Carcinoma, Renal Cell focused on measuring receptor tyrosine kinase inhibitor, programmed cell death 1 (PD-1, PD1), programmed cell death ligand 1 (PD-L1, PDL1)
Eligibility Criteria
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
Sites / Locations
- University of California at San Francisco ( Site 1008)Recruiting
- Yale-New Haven Hospital-Yale Cancer Center ( Site 1011)Recruiting
- University of Chicago ( Site 1013)Recruiting
- University of Iowa ( Site 1012)Recruiting
- Henry Ford Health System ( Site 1014)
- Laura and Isaac Perlmutter Cancer Center ( Site 1016)Recruiting
- Memorial Sloan Kettering Cancer Center ( Site 1002)Recruiting
- Duke Cancer Institute ( Site 1015)Recruiting
- UPMC Cancer Center/Hillman Cancer Center ( Site 1017)Recruiting
- UTSW Medical Center ( Site 1003)Recruiting
- Western Sydney Local Health District ( Site 1601)Recruiting
- St George Hospital ( Site 1602)Recruiting
- Royal Brisbane and Women s Hospital ( Site 1603)Recruiting
- Austin Health ( Site 1600)Recruiting
- Princess Margaret Cancer Centre ( Site 1101)Recruiting
- Jewish General Hospital ( Site 1100)Recruiting
- James Lind Centro de Investigación del Cáncer ( Site 2108)Recruiting
- CIDO SpA-Oncology ( Site 2106)Recruiting
- FALP-UIDO ( Site 2100)Recruiting
- Oncovida ( Site 2107)Recruiting
- Bradfordhill-Clinical Area ( Site 2101)Recruiting
- ONCOCENTRO APYS-ACEREY ( Site 2103)Recruiting
- Sociedad De Oncologia Y Hematologia Del Cesar-Oncology ( Site 1905)Recruiting
- Oncomédica S.A.S ( Site 1904)Recruiting
- Clinica Colsanitas S.A, Sede Clínica Universitaria Colombia-Center Investigator ( Site 1900)Recruiting
- Fundacion Valle del Lili- CIC ( Site 1901)Recruiting
- Institut De Cancerologie De Lorraine ( Site 1204)Recruiting
- Institut de cancérologie Strasbourg Europe (ICANS) ( Site 1203)Recruiting
- Institut Claudius Regaud ( Site 1200)Recruiting
- Gustave Roussy ( Site 1202)Recruiting
- Országos Onkológiai Intézet-Urogenitális Tumorok és Klinikai Farmakológiai Osztály ( Site 2301)Recruiting
- Rambam MC ( Site 1500)Recruiting
- Hadassah Medical Center-Oncology ( Site 1504)Recruiting
- Rabin Medical Center ( Site 1502)Recruiting
- Sheba Medical Center - Oncology Division ( Site 1501)Recruiting
- Sourasky Medical Center ( Site 1503)Recruiting
- Asan Medical Center ( Site 1800)Recruiting
- Severance Hospital ( Site 1802)Recruiting
- Samsung Medical Center ( Site 1801)Recruiting
- Nederlands Kanker Instituut - Antoni van Leeuwenhoek (NKI-AVL)-medical oncology ( Site 2402)Recruiting
- Erasmus Medisch Centrum ( Site 2401)Recruiting
- Auckland City Hospital ( Site 1700)Recruiting
- Centrum Onkologii im. Prof. Franciszka Lukaszczyka-Ambulatorium Chemioterapii ( Site 2201)Recruiting
- Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Oddzial Badan Wczesnych Faz ( Site 2200Recruiting
- Uniwersyteckie Centrum Kliniczne-Early Clinical Trials Unit ( Site 2202)Recruiting
- Hospital Universitari Vall d Hebron ( Site 1300)Recruiting
- Hospital Universitario Ramon y Cajal ( Site 1301)Recruiting
- Southampton General Hospital ( Site 1403)Recruiting
- The Beatson West of Scotland Cancer Centre ( Site 1405)Recruiting
- Royal Preston Hospital ( Site 1406)
- Leicester Royal Infirmary ( Site 1408)Recruiting
- Barts Health NHS Trust ( Site 1401)Recruiting
- Western General Hospital ( Site 1402)Recruiting
- Velindre Cancer Centre Hospital ( Site 1407)Recruiting
- The Christie NHS Foundation Trust ( Site 1400)Recruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Experimental
Experimental
Experimental
Experimental
Experimental
Coformulation Pembrolizumab/Quavonlimab + Lenvatinib
Coformulation Favezelimab/Pembrolizumab+ Lenvatinib
Pembrolizumab + Belzutifan + Lenvatinib
Pembrolizumab + Lenvatinib
Coformulation Vibostolimab/Pembrolizumab+Belzutifan
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.
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.
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.
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.
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.