Substudy 03B: A Study of Immune and Targeted Combination Therapies in Participants With Second Line Plus (2L+) Renal Cell Carcinoma (MK-3475-03B)
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 experienced disease progression on or after having received systemic. treatment for locally advanced or metastatic RCC with a PD-(L)1 checkpoint inhibitor (in sequence or in combination with a vascular endothelial growth factor. - tyrosine kinase inhibitor [VEGF-TKI]) where PD-(L)1 checkpoint inhibitor treatment progression is defined by meeting ALL of the following criteria: (a) has received ≥2 doses of an anti-PD-(L)1 monoclonal antibody (mAb) (b) has shown radiographic disease progression during or after an anti-PD-(L)1 mAb as defined by RECIST 1.1 by investigator (c) disease progression has been documented within 12 weeks from the last dose of an anti-PD-(L)1 mAb
- Has experienced disease progression on or after having received systemic treatment for locally advanced or metastatic RCC with a VEGF-TKI (in sequence or in combination with a PD-[L]1 checkpoint inhibitor) where VEGF-TKI treatment progression is defined by meeting the following criterion: has shown radiographic disease progression during or after a treatment with a VEGF-TKI as defined by RECIST 1.1 by investigator.
- 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 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, MK-4830 or a combination of the aforementioned drugs, no contraception is needed
- Female participant is not pregnant or breastfeeding and is not 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, MK-4830 or 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 previously received treatment with a combination of pembrolizumab plus lenvatinib
- Has received prior treatment with belzutifan
- 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 intervention; 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 3008)Recruiting
- Yale-New Haven Hospital-Yale Cancer Center ( Site 3011)Recruiting
- University of Chicago ( Site 3013)Recruiting
- University of Iowa ( Site 3012)Recruiting
- Henry Ford Health System ( Site 3014)
- Laura and Isaac Perlmutter Cancer Center ( Site 3016)Recruiting
- Memorial Sloan Kettering Cancer Center ( Site 3002)Recruiting
- Duke Cancer Institute ( Site 3015)Recruiting
- UPMC Cancer Center/Hillman Cancer Center ( Site 3017)Recruiting
- Vanderbilt University Medical Center ( Site 3004)Recruiting
- UTSW Medical Center ( Site 3003)Recruiting
- Western Sydney Local Health District ( Site 3601)Recruiting
- St George Hospital ( Site 3602)Recruiting
- Royal Brisbane and Women s Hospital ( Site 3603)Recruiting
- Austin Health ( Site 3600)Recruiting
- Princess Margaret Cancer Centre ( Site 3101)Recruiting
- Jewish General Hospital ( Site 3100)Recruiting
- James Lind Centro de Investigación del Cáncer ( Site 4108)Recruiting
- CIDO SpA-Oncology ( Site 4106)Recruiting
- FALP-UIDO ( Site 4100)Recruiting
- Bradfordhill-Clinical Area ( Site 4101)Recruiting
- ONCOCENTRO APYS-ACEREY ( Site 4103)Recruiting
- Institut De Cancerologie De Lorraine ( Site 3204)Recruiting
- Institut de cancérologie Strasbourg Europe (ICANS) ( Site 3203)Recruiting
- Institut Claudius Regaud ( Site 3200)Recruiting
- Gustave Roussy ( Site 3202)Recruiting
- Országos Onkológiai Intézet-Urogenitális Tumorok és Klinikai Farmakológiai Osztály ( Site 4301)Recruiting
- Rambam Health Care Campus-Oncology Division ( Site 3500)Recruiting
- Hadassah Medical Center-Oncology ( Site 3504)Recruiting
- Rabin Medical Center ( Site 3502)Recruiting
- Sheba Medical Center - Oncology Division ( Site 3501)Recruiting
- Sourasky Medical Center ( Site 3503)Recruiting
- Asan Medical Center ( Site 3800)Recruiting
- Severance Hospital ( Site 3802)
- Samsung Medical Center ( Site 3801)
- Nederlands Kanker Instituut - Antoni van Leeuwenhoek (NKI-AVL)-medical oncology ( Site 4402)Recruiting
- Erasmus Medisch Centrum ( Site 4401)Recruiting
- Auckland City Hospital ( Site 3700)Recruiting
- Centrum Onkologii im. Prof. Franciszka Lukaszczyka-Ambulatorium Chemioterapii ( Site 4201)Recruiting
- Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Oddzial Badan Wczesnych Faz ( Site 4200Recruiting
- Uniwersyteckie Centrum Kliniczne-Early Clinical Trials Unit ( Site 4202)Recruiting
- Hospital Universitari Vall d Hebron ( Site 3300)Recruiting
- Hospital Universitario Ramon y Cajal ( Site 3301)Recruiting
- Southampton General Hospital ( Site 3403)
- The Beatson West of Scotland Cancer Centre ( Site 3405)Recruiting
- Royal Preston Hospital ( Site 3406)
- Leicester Royal Infirmary ( Site 3408)Recruiting
- Barts Health NHS Trust ( Site 3401)
- Western General Hospital ( Site 3402)Recruiting
- Velindre Cancer Centre Hospital ( Site 3407)Recruiting
- The Christie NHS Foundation Trust ( Site 3400)Recruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Coformulation Pembrolizumab/Quavonlimab
Coformulation Favezelimab/Pembrolizumab
Pembrolizumab + MK-4830
Pembrolizumab + Belzutifan
Belzutifan + Lenvatinib
Pembrolizumab + Lenvatinib
Participants will receive pembrolizumab/quavonlimab (coformulation of pembrolizumab 400 mg and quavonlimab 25 mg). Pembrolizumab/quavonlimab will be administered intravenously (IV) once every 6 weeks (Q6W) for up to 17 administrations (up to ~2 years).
Participants will receive favezelimab/pembrolizumab (coformulation of favezelimab 800 mg and pembrolizumab 200 mg). Favezelimab/Pembrolizumab will be administered IV once every 3 weeks (Q3W) for up to 35 administrations (up to ~2 years).
Participants will receive pembrolizumab 200 mg PLUS MK-4830 800 mg. Both pembrolizumab and MK-4830 will be administered IV Q3W for up to 35 administrations (up to ~2 years).
Participants will receive pembrolizumab 400 mg PLUS belzutifan 120 mg. Pembrolizumab will be administered IV Q6W for up to 17 administrations (up to ~ 2 years). Belzutifan will be administered orally once-daily (QD) until progressive disease or discontinuation.
Participants will receive Belzutifan 120 mg PLUS lenvatinib 20 mg. 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.