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Renal Cell CarcinomaPhase 2KEYNOTE-B61NCT04704219

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

A Phase 2 study testing Pembrolizumab and Lenvatinib in people with Renal Cell Carcinoma, run by Merck Sharp & Dohme LLC at 56 sites in 14 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 120 years
Conditions the study is for
Renal Cell Carcinoma
What is being tested?
Pembrolizumab and Lenvatinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
160 participants
Where
56 sitesin 14 countries
Study dates
23 Feb 2021to 21 Oct 2025
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 120 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 10Show fewer
  • 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.

Who cannot join

  • 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.
Show all 25Show fewer
  • 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.
  • Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
  • Has known active CNS metastases and/or carcinomatous meningitis.
  • Has severe hypersensitivity (≥Grade 3) to pembrolizumab, lenvatinib and/or any of their excipients.
  • Has an active autoimmune disease that has required systemic treatment in past 2 years
  • Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
  • Has an active infection requiring systemic therapy.
  • Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority.
  • Has a known history of Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C virus.
  • Has a known history of active tuberculosis (TB; Bacillus tuberculosis).
  • Has had an allogenic tissue/solid organ transplant.

Trial locations and contacts

56 sites in 14 countries.

56 sites in 14 countries

United States8 sites

  • St. Vincent Frontier Cancer Center ( Site 0004)

    Billings, Montana, 59102

  • Comprehensive Cancer Centers of Nevada ( Site 0010)

    Las Vegas, Nevada, 89169

  • MEDICAL COLLEGE OF WISCONSIN ( Site 0006)

    Milwaukee, Wisconsin, 53226

  • Vanderbilt University Medical Center ( Site 0008)

    Nashville, Tennessee, 37232

  • Memorial Sloan Kettering Cancer Center ( Site 0015)

    New York, New York, 10065

  • Fox Chase Cancer Center ( Site 0011)

    Philadelphia, Pennsylvania, 19111

  • Seattle Cancer Care Alliance ( Site 0014)

    Seattle, Washington, 98109

  • Georgetown University Medical Center ( Site 0001)

    Washington D.C., District of Columbia, 20007

Other trials in United States

Australia6 sites

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

    Brisbane, Queensland, 4029

  • Monash Health ( Site 0400)

    Clayton, Victoria, 3168

  • Ashford Cancer Centre Research ( Site 0404)

    Kurralta Park, South Australia, 5037

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

    Macquarie Park, New South Wales, 2109

  • Fiona Stanley Hospital ( Site 0402)

    Murdoch, Western Australia, 6150

  • Calvary Mater Newcastle ( Site 0403)

    Waratah, New South Wales, 2298

Other trials in Australia

France5 sites

  • Centre François Baclesse ( Site 1000)

    Caen, Calvados, 14076

  • Centre de Cancérologie du Grand Montpellier ( Site 1005)

    Montpellier, Languedoc-Roussillon, 34070

  • centre hospitalier lyon sud ( Site 1003)

    Pierre-Bénite, Rhone, 69310

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

    Strasbourg, Alsace, 67200

  • Gustave Roussy ( Site 1002)

    Villejuif, Val-de-Marne, 94800

Other trials in France

Turkey (Türkiye)5 sites

  • Ankara University Hospital Cebeci ( Site 1105)

    Ankara, 06100

  • Hacettepe Universitesi-oncology hospital ( Site 1101)

    Ankara, 06230

  • Ege University Medicine of Faculty ( Site 1102)

    Bornova, İzmir, 35100

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

    Istanbul, 34722

  • Istanbul Universitesi Cerrahpasa ( Site 1104)

    Istanbul- Fatih, Istanbul, 34098

Other trials in Turkey (Türkiye)

Canada4 sites

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

    Québec, Quebec, G1R 3S1

  • Sunnybrook Health Sciences Centre ( Site 1501)

    Toronto, Ontario, M4N 3M5

  • Princess Margaret Cancer Centre ( Site 1504)

    Toronto, Ontario, M5G 2M9

  • BC Cancer Vancouver-Clinical Trials Unit ( Site 1500)

    Vancouver, British Columbia, V5Z 4E6

Other trials in Canada

Hungary4 sites

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

    Budapest, Pest County, 1122

  • Debreceni Egyetem Klinikai Kozpont-Onkológiai Klinika ( Site 0300)

    Debrecen, 4032

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

    Miskolc, Borsod-Abauj Zemplen county, 3526

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

    Szolnok, Jász-Nagykun-Szolnok, 5000

Other trials in Hungary

Italy4 sites

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

    Milan, Lombardy, 20133

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

    Rome, Lazio, 00168

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

    Terni, 05100

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

    Verona, Veneto, 37134

Other trials in Italy

Russia4 sites

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

    Moscow, Moscow, 117485

  • Volga District Medical Center-Urology Department ( Site 0604)

    Nizhny Novgorod, Nizhny Novgorod Oblast, 603074

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

    Nizhny Novgorod, Nizhny Novgorod Oblast, 603081

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

    Saint Petersburg, 188663

Other trials in Russia

Ukraine4 sites

  • Cherkasy Regional Oncology Dispensary ( Site 0504)

    Cherkassy, Cherkasy Oblast, 18009

  • Chernihiv Medical Center of Modern Oncology ( Site 0509)

    Chernihiv, Chernihiv Oblast, 14029

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

    Dnipro, Dnipropetrovsk Oblast, 49005

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

    Kharkiv, Kharkiv Oblast, 61070

Other trials in Ukraine

Poland3 sites

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

    Poznan, Greater Poland Voivodeship, 60-569

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

    Warsaw, Masovian Voivodeship, 01-748

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

    Warsaw, Masovian Voivodeship, 02-781

Other trials in Poland

South Korea3 sites

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

    Seoul, 03722

  • Asan Medical Center-Department of Oncology ( Site 1300)

    Seoul, 05505

  • Samsung Medical Center ( Site 1301)

    Seoul, 06351

Other trials in South Korea

Spain3 sites

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

    Barcelona, 08035

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

    Madrid, Madrid, Comunidad de, 28034

  • Fundación Instituto Valenciano de Oncología-Oncologico ( Site 0202)

    Valencia, Valenciana, Comunitat, 46009

Other trials in Spain

United Kingdom2 sites

  • Cambridge University Hospital ( Site 1200)

    Cambridge, England, CB2 0QQ

  • The Christie ( Site 1205)

    Manchester, M20 4BX

Other trials in United Kingdom

Ireland1 site

  • Tallaght University Hospital ( Site 1600)

    Dublin, D24 NR0A

Other trials in Ireland

About this study

Official title: A Phase 2, Single-arm, Open-label Clinical Trial of Pembrolizumab Plus Lenvatinib in Participants With First-line Advanced/Metastatic Non-clear Cell Renal Cell Carcinoma (nccRCC) (KEYNOTE-B61)

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.

Keywords
Programmed Cell Death-1 (PD1, PD-1), Programmed Death-Ligand 1 (PDL1, PD-L1), Pembrolizumab, Lenvatinib
Medical subject headings
Carcinoma, Renal Cell, Parkinson Disease 4, Autosomal Dominant Lewy Body

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PembrolizumabBiological

    Also called KEYTRUDA®, MK-3475

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

  • LenvatinibDrug

    Also called LENVIMA®, Kisplyx, MK-7902, E7080

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

Study groups in NCT04704219
Study groupRoleWhat they receive
Pembrolizumab + LenvatinibExperimentalPembrolizumab 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.
Receives: Biological: Pembrolizumab; Drug: Lenvatinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to approximately 47 months

Secondary outcomes (7)

  1. Duration of Response (DOR)

    For participants who demonstrate a confirmed 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) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), DOR was defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. Duration of response per RECIST 1.1 by Blinded Independent Central Review (BICR) is presented.

    Measured: Up to approximately 47 months

  2. Progression Free Survival (PFS)

    PFS was defined as the time from date of study treatment to the first documented progressive disease (PD) based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The percentage of participants who experienced PFS per RECIST 1.1 by Blinded Independent Central Review (BICR) is presented.

    Measured: Up to approximately 47 months

  3. Overall Survival (OS)

    OS was defined as the time from the date of study treatment to the date of death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. The OS for all participants is presented.

    Measured: Up to approximately 47 months

  4. Clinical Benefit Rate (CBR)

    CBR is defined as the percentage of participants who have achieved 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 or Stable Disease (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm]) of ≥6 months per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR).

    Measured: Up to approximately 47 months

  5. Disease Control Rate (DCR)

    DCR was defined per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as the percentage of participants 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) or Stable Disease (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm]). The appearance of one or more new lesions is also considered PD]). Disease Control rate per RECIST 1.1 by Blinded Independent Central Review (BICR) is presented.

    Measured: Up to approximately 47 months

  6. Number of Participants With One or More Adverse Events (AEs)

    An AE was defined as 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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants with at least one or more AE is presented.

    Measured: Up to approximately 55 months

  7. Number of Participants Who Discontinued From Study Treatment Due to an AE

    An AE was defined as 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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants with at least one or more AE is presented.

    Measured: Up to approximately 55 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Jan 2021
  2. Study start23 Feb 2021
  3. Primary completion27 Jan 2025
  4. Study completion21 Oct 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
160 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04704219
Sponsor's protocol ID
3475-B61
Other IDs
MK-3475-B61, 2023-504944-32-00, U1111-1290-4553, 2020-004087-26, 2023
Acronym
KEYNOTE-B61
Status last verified
Oct 2026
First submitted
7 Jan 2021
Last updated
3 Nov 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Publications

  • 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.

    PubMed 37451291

  • 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.

    PubMed 40707309

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pembrolizumab and Lenvatinib in people with Renal Cell Carcinoma, run by Merck Sharp & Dohme LLC at 56 sites in 14 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 56 sites in United States, Australia, France, Turkey (Türkiye), Canada and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Dec 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (ORR) (time frame: Up to approximately 47 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04704219, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2026.

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