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

Renal Cell Carcinoma Clinical Trial

— KEYNOTE-B61  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04704219
• Other study ID #: 3475-B61
• Secondary ID: MK-3475-B612020-
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: February 23, 2021
• Est. completion date: October 22, 2025

Study information

• Verified date: January 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 152
• Est. completion date: October 22, 2025
• Est. primary completion date: August 16, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

Inclusion Criteria:

1. Must have a histologically-confirmed diagnosis of non-clear cell RCC.

2. Has locally advanced/metastatic disease (ie, Stage IV per the American Joint Committee on Cancer).

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. Has Karnofsky Performance Status (KPS) =70% as assessed within 10 days prior to the start of study intervention.

9. Has adequately controlled blood pressure with or without antihypertensive medications

10. Have adequate organ function.

Exclusion Criteria:

1. Has collecting duct histology.

2. A WOCBP who has a positive urine pregnancy test within 24 hours before the first dose of study intervention.

3. Has a left ventricular ejection fraction below the institutional (or local laboratory) normal range.

4. Has radiographic encasement or invasion of a major blood vessel, or of intratumoral cavitation.

5. Has clinically significant cardiovascular disease within 12 months from first dose of study intervention.

6. Has gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib.

7. Has active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug.

8. Has had major surgery within 3 weeks prior to first dose of study intervention.

9. 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).

10. Has received prior systemic anticancer therapy including investigational agents within 4 weeks prior to allocation.

11. 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.

12. Has received a live or attenuated vaccine within 30 days before the first dose of study intervention.

13. 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.

14. 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.

15. 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.

16. Has known active CNS metastases and/or carcinomatous meningitis.

17. Has severe hypersensitivity (=Grade 3) to pembrolizumab, lenvatinib and/or any of their excipients.

18. Has an active autoimmune disease that has required systemic treatment in past 2 years

19. Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.

20. Has an active infection requiring systemic therapy.

21. Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority.

22. Has a known history of Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C virus.

23. Has a known history of active tuberculosis (TB; Bacillus tuberculosis).

24. Has had an allogenic tissue/solid organ transplant.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Renal Cell Carcinoma

Intervention

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

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

Locations

Country	Name	City	State
Australia	Royal Brisbane and Women's Hospital-Medical Oncology Clinical Trials Unit, Cancer Care Services ( Si	Brisbane	Queensland
Australia	Monash Health ( Site 0400)	Clayton	Victoria
Australia	Ashford Cancer Centre Research ( Site 0404)	Kurralta Park	South Australia
Australia	Macquarie University-MQ Health Clinical Trials Unit ( Site 0405)	Macquarie Park	New South Wales
Australia	Fiona Stanley Hospital ( Site 0402)	Murdoch	Western Australia
Australia	Calvary Mater Newcastle ( Site 0403)	Waratah	New South Wales
Canada	CHU de Quebec - Université Laval - Hotel Dieu de Quebec ( Site 1502)	Québec	Quebec
Canada	Princess Margaret Cancer Centre ( Site 1504)	Toronto	Ontario
Canada	Sunnybrook Health Sciences Centre ( Site 1501)	Toronto	Ontario
Canada	BC Cancer Vancouver-Clinical Trials Unit ( Site 1500)	Vancouver	British Columbia
France	Centre François Baclesse ( Site 1000)	Caen	Calvados
France	Centre de Cancérologie du Grand Montpellier ( Site 1005)	Montpellier	Languedoc-Roussillon
France	centre hospitalier lyon sud ( Site 1003)	Pierre-Bénite	Rhone
France	Institut de cancérologie Strasbourg Europe (ICANS) ( Site 1007)	Strasbourg	Alsace
France	Gustave Roussy ( Site 1002)	Villejuif	Val-de-Marne
Hungary	Országos Onkológiai Intézet-Urogenital Tumors Department and Clinical Pharmacology ( Site 0304)	Budapest	Pest
Hungary	Debreceni Egyetem Klinikai Kozpont-Onkológiai Klinika ( Site 0300)	Debrecen
Hungary	Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Okta-Klinikai Onkológiai és Sugárterápiás C	Miskolc	Borsod-Abauj-Zemplen
Hungary	Jász-Nagykun-Szolnok Megyei Hetényi Géza Kórház-Onkologiai Kozpont ( Site 0303)	Szolnok	Jasz-Nagykun-Szolnok
Ireland	Tallaght University Hospital ( Site 1600)	Dublin
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 0903)	Milan	Lombardia
Italy	Fondazione Policlinico Universitario Agostino Gemelli-Medical Oncology ( Site 0901)	Roma	Lazio
Italy	Azienda Ospedaliera Santa Maria Terni-SC Oncologia ( Site 0900)	Terni
Italy	Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Borgo Roma-Oncology Unit ( Site 0902)	Verona	Veneto
Korea, Republic of	Asan Medical Center-Department of Oncology ( Site 1300)	Seoul
Korea, Republic of	Samsung Medical Center ( Site 1301)	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System-Medical oncology ( Site 1302)	Seoul
Poland	Szpital Kliniczny im. Przemienienia Panskiego Uniwersytetu M-chemotherapy department ( Site 0800)	Poznan	Wielkopolskie
Poland	Luxmed Onkologia sp. z o. o. ( Site 0802)	Warszawa	Mazowieckie
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie (	Warszawa	Mazowieckie
Russian Federation	Russian Scientific Center of Radiology-Russian Scientific Center of Radiology ( Site 0602)	Moscow	Moskva
Russian Federation	Nizhegorodsky Regional Oncology Dispensary, Branch #2-chemotherapy ( Site 0605)	Nizhniy Novgorod	Nizhegorodskaya Oblast
Russian Federation	Volga District Medical Center-Urology Department ( Site 0604)	Nizhny Novgorod	Nizhegorodskaya Oblast
Russian Federation	SHBI Leningrad Regional Clinical Oncology Dispensary-Clinical Trials Department ( Site 0607)	Sankt-Peterburg
Spain	Hospital Universitari Vall d'Hebron-Departamento de Oncologia- VHIO ( Site 0201)	Barcelona
Spain	Hospital Universitario Ramón y Cajal-Medical Oncology ( Site 0200)	Madrid	Madrid, Comunidad De
Spain	Fundación Instituto Valenciano de Oncología-Oncologico ( Site 0202)	Valencia	Valenciana, Comunitat
Turkey	Ankara University Hospital Cebeci ( Site 1105)	Ankara
Turkey	Hacettepe Universitesi-oncology hospital ( Site 1101)	Ankara
Turkey	Ege University Medicine of Faculty ( Site 1102)	Bornova	Izmir
Turkey	Göztepe Prof. Dr. Süleyman Yalçin Sehir Hastanesi-oncology ( Site 1103)	Istanbul
Turkey	Istanbul Universitesi Cerrahpasa ( Site 1104)	Istanbul- Fatih	Istanbul
Ukraine	Cherkasy Regional Oncology Dispensary ( Site 0504)	Cherkassy	Cherkaska Oblast
Ukraine	Chernihiv Medical Center of Modern Oncology ( Site 0509)	Chernihiv	Chernihivska Oblast
Ukraine	Dnepropetrovsk Regional Clinical Hospital Mechnikov-Department of urology ( Site 0508)	Dnipro	Dnipropetrovska Oblast
Ukraine	CNPE "Regional Center of Oncology"-oncourology department ( Site 0502)	Kharkiv	Kharkivska Oblast
United Kingdom	Cambridge University Hospital ( Site 1200)	Cambridge	England
United Kingdom	The Christie ( Site 1205)	Manchester
United States	St. Vincent Frontier Cancer Center ( Site 0004)	Billings	Montana
United States	Comprehensive Cancer Centers of Nevada ( Site 0010)	Las Vegas	Nevada
United States	MEDICAL COLLEGE OF WISCONSIN ( Site 0006)	Milwaukee	Wisconsin
United States	Vanderbilt University Medical Center ( Site 0008)	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center ( Site 0015)	New York	New York
United States	Fox Chase Cancer Center ( Site 0011)	Philadelphia	Pennsylvania
United States	Seattle Cancer Care Alliance ( Site 0014)	Seattle	Washington
United States	Georgetown University Medical Center ( Site 0001)	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC	Eisai Inc.

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Hungary,  Ireland,  Italy,  Korea, Republic of,  Poland,  Russian Federation,  Spain,  Turkey,  Ukraine,  United Kingdom, 

References & Publications (1)

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 advance — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR)	Objective Response Rate (ORR) is defined as the percentage of participants with a complete response (CR) or partial response (PR) per response evaluation criteria in solid tumors 1.1 (RECIST 1.1) by blinded independent central review (BICR).	Up to approximately 3 years
Secondary	Duration of Response (DOR)	Duration of Response (DOR) is defined for participants who demonstrate confirmed CR or PR as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first.	Up to approximately 4.5 years
Secondary	Progression-free Survival (PFS)	Progression-free Survival (PFS) is defined as the time from the date of first dose to the first documented progressive disease (PD) per RECIST 1.1 by BICR or death from any cause, whichever occurs first.	Up to approximately 4.5 years
Secondary	Overall Survival (OS)	Overall Survival (OS) is defined as the time from date of first dose until death from any cause.	Up to approximately 4.5 years
Secondary	Clinical Benefit Ratio (CBR)	Clinical Benefit Ratio (CBR) is defined as the percentage of participants who achieved CR, PR, or stable disease (SD) for at least 6 months per RECIST 1.1 by BICR.	Up to approximately 4.5 years
Secondary	Disease Control Rate (DCR)	Disease Control Rate (DCR) is defined as the percentage of participants who achieved CR, PR, or SD per RECIST 1.1 by BICR.	Up to approximately 4.5 years
Secondary	Number of Participants Who Experienced One or More Adverse Events (AEs)	An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.	Up to approximately 4.5 years
Secondary	Number of Participants Who Discontinued Study Medication Due to an AE	An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.	Up to approximately 4.5 years

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary