Pembrolizumab Plus Lenvatinib for First-line Advanced/Metastatic Non-clear Cell Renal Cell Carcinoma (1L nccRCC) (MK-3475-B61)

NCT04704219 | Completed Phase 2 Results FDA Drug

• 5 other identifiers: 3475-B61MK-3475-B612023-504944-32-00U1111-1290-45532020-004087-26
• Study Type: interventional
• Target: 160
• Locations: 14 countries
• Sites: 56

Brief Summary

This study is being performed as a single-arm open-label study in order to rapidly provide information on the potential benefits of the combination of pembrolizumab and lenvatinib in participants with previously untreated advanced/metastatic non-clear cell renal cell carcinoma.

Conditions

Renal Cell Carcinoma

Keywords

Programmed Cell Death-1 (PD1, PD-1); Programmed Death-Ligand 1 (PDL1, PD-L1); Pembrolizumab; Lenvatinib

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR was defined as the percentage of participants who had a best overall response of either 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 as assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experienced a CR or PR as assessed per RECIST 1.1 by blinded independent central review (BICR) is presented.

  Up to approximately 47 months

Secondary Outcomes (7)

• Duration of Response (DOR)

  Up to approximately 47 months

• Progression Free Survival (PFS)

  Up to approximately 47 months

• Overall Survival (OS)

  Up to approximately 47 months

• Clinical Benefit Rate (CBR)

  Up to approximately 47 months

• Disease Control Rate (DCR)

  Up to approximately 47 months

Study Arms (1)

Pembrolizumab + Lenvatinib

EXPERIMENTAL

Pembrolizumab 400 mg, every 6 weeks (Q6W) intravenous (IV) up to 18 infusions or up to progressive disease or discontinuation PLUS Lenvatinib 20 mg, daily (QD), oral, until progressive disease or discontinuation.

Biological: Pembrolizumab; Drug: Lenvatinib

Interventions

Pembrolizumab BIOLOGICAL

Pembrolizumab 400 mg, every 6 weeks (Q6W) intravenous (IV) up to 18 infusions or up to progressive disease or discontinuation.

Also known as: KEYTRUDA®, MK-3475

Pembrolizumab + Lenvatinib

Lenvatinib DRUG

Lenvatinib 20 mg, daily (QD), oral, until progressive disease or discontinuation.

Also known as: LENVIMA®, Kisplyx, MK-7902, E7080

Pembrolizumab + Lenvatinib

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must have a histologically confirmed diagnosis of nccRCC.
• Has locally advanced/metastatic disease (ie, Stage IV per the American Joint Committee on Cancer).
• Has received no prior systemic therapy for advanced nccRCC. Note: Prior neoadjuvant/adjuvant therapy for nccRCC is acceptable if completed \>12 months prior to allocation.
• Male participants agree to use approved contraception during the treatment period for at least 7 days after the last dose of study medication, or refrain from heterosexual intercourse during this period.
• Female participants are not pregnant or breastfeeding, and are not a woman of childbearing potential (WOCBP), OR are a WOCBP that agrees to use contraception during the treatment period and for at least 120 days post pembrolizumab, or 30 days post lenvatinib, whichever occurs last.
• Has measurable disease per RECIST 1.1 as assessed by BICR. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Has submitted an archival tumor tissue sample or newly obtained core or incisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.
• Has Karnofsky Performance Status (KPS) ≥70% as assessed within 10 days prior to the start of study intervention.
• Has adequately controlled blood pressure with or without antihypertensive medications
• Have adequate organ function.

You may not qualify if:

• Has collecting duct histology.
• A WOCBP who has a positive urine pregnancy test within 24 hours before the first dose of study intervention.
• Has a left ventricular ejection fraction below the institutional (or local laboratory) normal range.
• Has radiographic encasement or invasion of a major blood vessel, or of intratumoral cavitation.
• Has clinically significant cardiovascular disease within 12 months from first dose of study intervention.
• Has gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib.
• Has active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug.
• Has had major surgery within 3 weeks prior to first dose of study intervention.
• Has received prior therapy with an anti-programmed cell-death 1 (PD-1), anti-programmed cell-death ligand 1 (PD-L1), or anti-programmed cell-death ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137).
• Has received prior systemic anticancer therapy including investigational agents within 4 weeks prior to allocation.
• Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
• Has received a live or attenuated vaccine within 30 days before the first dose of study intervention.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention.
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead
• Eisai Inc.: collaborator

Study Sites (56)

Georgetown University Medical Center ( Site 0001)

Washington D.C., District of Columbia, 20007, United States

Location

St. Vincent Frontier Cancer Center ( Site 0004)

Billings, Montana, 59102, United States

Location

Comprehensive Cancer Centers of Nevada ( Site 0010)

Las Vegas, Nevada, 89169, United States

Location

Memorial Sloan Kettering Cancer Center ( Site 0015)

New York, New York, 10065, United States

Location

Fox Chase Cancer Center ( Site 0011)

Philadelphia, Pennsylvania, 19111, United States

Location

Vanderbilt University Medical Center ( Site 0008)

Nashville, Tennessee, 37232, United States

Location

Seattle Cancer Care Alliance ( Site 0014)

Seattle, Washington, 98109, United States

Location

MEDICAL COLLEGE OF WISCONSIN ( Site 0006)

Milwaukee, Wisconsin, 53226, United States

Location

Macquarie University-MQ Health Clinical Trials Unit ( Site 0405)

Macquarie Park, New South Wales, 2109, Australia

Location

Calvary Mater Newcastle ( Site 0403)

Waratah, New South Wales, 2298, Australia

Location

Royal Brisbane and Women's Hospital-Medical Oncology Clinical Trials Unit, Cancer Care Services ( Si

Brisbane, Queensland, 4029, Australia

Location

Ashford Cancer Centre Research ( Site 0404)

Kurralta Park, South Australia, 5037, Australia

Location

Monash Health ( Site 0400)

Clayton, Victoria, 3168, Australia

Location

Fiona Stanley Hospital ( Site 0402)

Murdoch, Western Australia, 6150, Australia

Location

BC Cancer Vancouver-Clinical Trials Unit ( Site 1500)

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Sunnybrook Health Sciences Centre ( Site 1501)

Toronto, Ontario, M4N 3M5, Canada

Location

Princess Margaret Cancer Centre ( Site 1504)

Toronto, Ontario, M5G 2M9, Canada

Location

CHU de Quebec - Université Laval - Hotel Dieu de Quebec ( Site 1502)

Québec, Quebec, G1R 3S1, Canada

Location

Institut de cancérologie Strasbourg Europe (ICANS) ( Site 1007)

Strasbourg, Alsace, 67200, France

Location

Centre François Baclesse ( Site 1000)

Caen, Calvados, 14076, France

Location

Centre de Cancérologie du Grand Montpellier ( Site 1005)

Montpellier, Languedoc-Roussillon, 34070, France

Location

centre hospitalier lyon sud ( Site 1003)

Pierre-Bénite, Rhone, 69310, France

Location

Gustave Roussy ( Site 1002)

Villejuif, Val-de-Marne, 94800, France

Location

Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Okta-Klinikai Onkológiai és Sugárterápiás C

Miskolc, Borsod-Abauj Zemplen county, 3526, Hungary

Location

Jász-Nagykun-Szolnok Megyei Hetényi Géza Kórház-Onkologiai Kozpont ( Site 0303)

Szolnok, Jász-Nagykun-Szolnok, 5000, Hungary

Location

Országos Onkológiai Intézet-Urogenital Tumors Department and Clinical Pharmacology ( Site 0304)

Budapest, Pest County, 1122, Hungary

Location

Debreceni Egyetem Klinikai Kozpont-Onkológiai Klinika ( Site 0300)

Debrecen, 4032, Hungary

Location

Tallaght University Hospital ( Site 1600)

Dublin, D24 NR0A, Ireland

Location

Fondazione Policlinico Universitario Agostino Gemelli-Medical Oncology ( Site 0901)

Rome, Lazio, 00168, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 0903)

Milan, Lombardy, 20133, Italy

Location

Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Borgo Roma-Oncology Unit ( Site 0902)

Verona, Veneto, 37134, Italy

Location

Azienda Ospedaliera Santa Maria Terni-SC Oncologia ( Site 0900)

Terni, 05100, Italy

Location

Szpital Kliniczny im. Przemienienia Panskiego Uniwersytetu M-chemotherapy department ( Site 0800)

Poznan, Greater Poland Voivodeship, 60-569, Poland

Location

Luxmed Onkologia sp. z o. o. ( Site 0802)

Warsaw, Masovian Voivodeship, 01-748, Poland

Location

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie (

Warsaw, Masovian Voivodeship, 02-781, Poland

Location

Russian Scientific Center of Radiology-Russian Scientific Center of Radiology ( Site 0602)

Moscow, Moscow, 117485, Russia

Location

Volga District Medical Center-Urology Department ( Site 0604)

Nizhny Novgorod, Nizhny Novgorod Oblast, 603074, Russia

Location

Nizhegorodsky Regional Oncology Dispensary, Branch #2-chemotherapy ( Site 0605)

Nizhny Novgorod, Nizhny Novgorod Oblast, 603081, Russia

Location

SHBI Leningrad Regional Clinical Oncology Dispensary-Clinical Trials Department ( Site 0607)

Saint Petersburg, 188663, Russia

Location

Severance Hospital, Yonsei University Health System-Medical oncology ( Site 1302)

Seoul, 03722, South Korea

Location

Asan Medical Center-Department of Oncology ( Site 1300)

Seoul, 05505, South Korea

Location

Samsung Medical Center ( Site 1301)

Seoul, 06351, South Korea

Location

Hospital Universitario Ramón y Cajal-Medical Oncology ( Site 0200)

Madrid, Madrid, Comunidad de, 28034, Spain

Location

Fundación Instituto Valenciano de Oncología-Oncologico ( Site 0202)

Valencia, Valenciana, Comunitat, 46009, Spain

Location

Hospital Universitari Vall d'Hebron-Departamento de Oncologia- VHIO ( Site 0201)

Barcelona, 08035, Spain

Location

Istanbul Universitesi Cerrahpasa ( Site 1104)

Istanbul- Fatih, Istanbul, 34098, Turkey (Türkiye)

Location

Ege University Medicine of Faculty ( Site 1102)

Bornova, İzmir, 35100, Turkey (Türkiye)

Location

Ankara University Hospital Cebeci ( Site 1105)

Ankara, 06100, Turkey (Türkiye)

Location

Hacettepe Universitesi-oncology hospital ( Site 1101)

Ankara, 06230, Turkey (Türkiye)

Location

Göztepe Prof. Dr. Süleyman Yalçın Şehir Hastanesi-oncology ( Site 1103)

Istanbul, 34722, Turkey (Türkiye)

Location

Cherkasy Regional Oncology Dispensary ( Site 0504)

Cherkassy, Cherkasy Oblast, 18009, Ukraine

Location

Chernihiv Medical Center of Modern Oncology ( Site 0509)

Chernihiv, Chernihiv Oblast, 14029, Ukraine

Location

Dnepropetrovsk Regional Clinical Hospital Mechnikov-Department of urology ( Site 0508)

Dnipro, Dnipropetrovsk Oblast, 49005, Ukraine

Location

CNPE "Regional Center of Oncology"-oncourology department ( Site 0502)

Kharkiv, Kharkivs’ka Oblast’, 61070, Ukraine

Location

Cambridge University Hospital ( Site 1200)

Cambridge, England, CB2 0QQ, United Kingdom

Location

The Christie ( Site 1205)

Manchester, M20 4BX, United Kingdom

Location

Related Publications (2)

• Albiges L, Gurney H, Atduev V, Suarez C, Climent MA, Pook D, Tomczak P, Barthelemy P, Lee JL, Stus V, Ferguson T, Wiechno P, Gokmen E, Lacombe L, Gedye C, Perini RF, Sharma M, Peng X, Lee CH. Pembrolizumab plus lenvatinib as first-line therapy for advanced non-clear-cell renal cell carcinoma (KEYNOTE-B61): a single-arm, multicentre, phase 2 trial. Lancet Oncol. 2023 Aug;24(8):881-891. doi: 10.1016/S1470-2045(23)00276-0. Epub 2023 Jul 11.

  PMID: 37451291 RESULT

• Voss MH, Gurney H, Atduev V, Suarez C, Climent MA, Pook D, Tomczak P, Barthelemy P, Lee JL, Nalbandian T, Stus V, Ferguson T, Wiechno P, Gokmen E, Lacombe L, Gedye C, Cornell J, Sharma M, Burgents JE, Albiges L. First-line Pembrolizumab Plus Lenvatinib for Advanced Non-clear-cell Renal Cell Carcinoma: Updated Results from the Phase 2 KEYNOTE-B61 Trial. Eur Urol. 2025 Dec;88(6):614-624. doi: 10.1016/j.eururo.2025.05.019. Epub 2025 Jul 24.

  PMID: 40707309 RESULT

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Carcinoma, Renal Cell; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab; lenvatinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@msd.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2021
• First Posted: January 11, 2021
• Study Start: February 23, 2021
• Primary Completion: January 27, 2025
• Study Completion: October 21, 2025
• Last Updated: December 3, 2025
• Results First Posted: December 3, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share

Locations

TU (5); UA (4); FR (5); RU (4); AU (6); GB (2); US (8); CA (4); HU (4); IE (1); ES (3); IT (4); PL (3); KR (3)