Clinical trial NCT04704219: Pembrolizumab Plus Lenvatinib for First-line Advanced/Metastatic Non-clear Cell Renal Cell Carcinoma (1L nccRCC) (MK-3475-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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Renal Cell Carcinoma
Keywords: Programmed Cell Death-1 (PD1, PD-1)
Programmed Death-Ligand 1 (PDL1, PD-L1)
Pembrolizumab
Lenvatinib
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
Collaborators: name: Eisai Inc.
First posted: 2021-01-11
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Must have a histologically confirmed diagnosis of nccRCC.
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.

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 3 years
Secondary outcomes:
measure: Duration of Response (DOR)
timeFrame: Up to approximately 4.5 years
measure: Progression-free Survival (PFS)
timeFrame: Up to approximately 4.5 years
measure: Overall Survival (OS)
timeFrame: Up to approximately 4.5 years
measure: Clinical Benefit Ratio (CBR)
timeFrame: Up to approximately 4.5 years
measure: Disease Control Rate (DCR)
timeFrame: Up to approximately 4.5 years
measure: Number of Participants Who Experienced One or More Adverse Events (AEs)
timeFrame: Up to approximately 4.5 years
measure: Number of Participants Who Discontinued Study Medication Due to an AE
timeFrame: Up to approximately 4.5 years
Other outcomes:
Locations:
city: Washington
country: United States
facility: Georgetown University Medical Center ( Site 0001)
state: District of Columbia
city: Billings
country: United States
facility: St. Vincent Frontier Cancer Center ( Site 0004)
state: Montana
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada ( Site 0010)
state: Nevada
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center ( Site 0015)
state: New York
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center ( Site 0011)
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center ( Site 0008)
state: Tennessee
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance ( Site 0014)
state: Washington
city: Milwaukee
country: United States
facility: MEDICAL COLLEGE OF WISCONSIN ( Site 0006)
state: Wisconsin
city: Macquarie Park
country: Australia
facility: Macquarie University-MQ Health Clinical Trials Unit ( Site 0405)
state: New South Wales
city: Waratah
country: Australia
facility: Calvary Mater Newcastle ( Site 0403)
state: New South Wales
city: Brisbane
country: Australia
facility: Royal Brisbane and Women's Hospital-Medical Oncology Clinical Trials Unit, Cancer Care Services ( Si
state: Queensland
city: Kurralta Park
country: Australia
facility: Ashford Cancer Centre Research ( Site 0404)
state: South Australia
city: Clayton
country: Australia
facility: Monash Health ( Site 0400)
state: Victoria
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital ( Site 0402)
state: Western Australia
city: Vancouver
country: Canada
facility: BC Cancer Vancouver-Clinical Trials Unit ( Site 1500)
state: British Columbia
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre ( Site 1501)
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre ( Site 1504)
state: Ontario
city: Québec
country: Canada
facility: CHU de Quebec - Université Laval - Hotel Dieu de Quebec ( Site 1502)
state: Quebec
city: Strasbourg
country: France
facility: Institut de cancérologie Strasbourg Europe (ICANS) ( Site 1007)
state: Alsace
city: Caen
country: France
facility: Centre François Baclesse ( Site 1000)
state: Calvados
city: Montpellier
country: France
facility: Centre de Cancérologie du Grand Montpellier ( Site 1005)
state: Languedoc-Roussillon
city: Pierre-Bénite
country: France
facility: centre hospitalier lyon sud ( Site 1003)
state: Rhone
city: Villejuif
country: France
facility: Gustave Roussy ( Site 1002)
state: Val-de-Marne
city: Miskolc
country: Hungary
facility: Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Okta-Klinikai Onkológiai és Sugárterápiás C
state: Borsod-Abauj-Zemplen
city: Szolnok
country: Hungary
facility: Jász-Nagykun-Szolnok Megyei Hetényi Géza Kórház-Onkologiai Kozpont ( Site 0303)
state: Jasz-Nagykun-Szolnok
city: Budapest
country: Hungary
facility: Országos Onkológiai Intézet-Urogenital Tumors Department and Clinical Pharmacology ( Site 0304)
state: Pest
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont-Onkológiai Klinika ( Site 0300)
city: Dublin
country: Ireland
facility: Tallaght University Hospital ( Site 1600)
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli-Medical Oncology ( Site 0901)
state: Lazio
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 0903)
state: Lombardia
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Borgo Roma-Oncology Unit ( Site 0902)
state: Veneto
city: Terni
country: Italy
facility: Azienda Ospedaliera Santa Maria Terni-SC Oncologia ( Site 0900)
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System-Medical oncology ( Site 1302)
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center-Department of Oncology ( Site 1300)
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center ( Site 1301)
city: Warszawa
country: Poland
facility: Luxmed Onkologia sp. z o. o. ( Site 0802)
state: Mazowieckie
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie (
state: Mazowieckie
city: Poznań
country: Poland
facility: Szpital Kliniczny im. Przemienienia Panskiego Uniwersytetu M-chemotherapy department ( Site 0800)
state: Wielkopolskie
city: Moscow
country: Russian Federation
facility: Russian Scientific Center of Radiology-Russian Scientific Center of Radiology ( Site 0602)
state: Moskva
city: Nizhniy Novgorod
country: Russian Federation
facility: Nizhegorodsky Regional Oncology Dispensary, Branch #2-chemotherapy ( Site 0605)
state: Nizhegorodskaya Oblast
city: Nizhny Novgorod
country: Russian Federation
facility: Volga District Medical Center-Urology Department ( Site 0604)
state: Nizhegorodskaya Oblast
city: Sankt-Peterburg
country: Russian Federation
facility: SHBI Leningrad Regional Clinical Oncology Dispensary-Clinical Trials Department ( Site 0607)
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal-Medical Oncology ( Site 0200)
state: Madrid, Comunidad De
city: Valencia
country: Spain
facility: Fundación Instituto Valenciano de Oncología-Oncologico ( Site 0202)
state: Valenciana, Comunitat
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron-Departamento de Oncologia- VHIO ( Site 0201)
city: Istanbul- Fatih
country: Turkey
facility: Istanbul Universitesi Cerrahpasa ( Site 1104)
state: Istanbul
city: Bornova
country: Turkey
facility: Ege University Medicine of Faculty ( Site 1102)
state: Izmir
city: Ankara
country: Turkey
facility: Ankara University Hospital Cebeci ( Site 1105)
city: Ankara
country: Turkey
facility: Hacettepe Universitesi-oncology hospital ( Site 1101)
city: Istanbul
country: Turkey
facility: Göztepe Prof. Dr. Süleyman Yalçın Şehir Hastanesi-oncology ( Site 1103)
city: Cherkassy
country: Ukraine
facility: Cherkasy Regional Oncology Dispensary ( Site 0504)
state: Cherkaska Oblast
city: Chernihiv
country: Ukraine
facility: Chernihiv Medical Center of Modern Oncology ( Site 0509)
state: Chernihivska Oblast
city: Dnipro
country: Ukraine
facility: Dnepropetrovsk Regional Clinical Hospital Mechnikov-Department of urology ( Site 0508)
state: Dnipropetrovska Oblast
city: Kharkiv
country: Ukraine
facility: CNPE "Regional Center of Oncology"-oncourology department ( Site 0502)
state: Kharkivska Oblast
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospital ( Site 1200)
state: England
city: Manchester
country: United Kingdom
facility: The Christie ( Site 1205)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.