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

Phase 2

Active, not recruiting

• Conditions: Renal Cell Carcinoma
• Interventions: Biological: Pembrolizumab; Drug: Lenvatinib

• Registration Number: NCT04704219
• Lead Sponsor: Merck Sharp & Dohme LLC

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-01-07
• Study First Submitted QC: 2021-01-07
• Study First Posted: 2021-01-11
• Study Start: 2021-02-23
• Primary Completion: 2025-01-27
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-14
• Last Update Posted: 2025-02-17
• Study Completion: 2025-10-25

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 160

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Pembrolizumab + Lenvatinib	Lenvatinib	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.
Pembrolizumab + Lenvatinib	Pembrolizumab	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.

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	Up to approximately 3 years	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).

Secondary Outcome Measures

Name	Time	Method
Duration of Response (DOR)	Up to approximately 4.5 years	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.
Overall Survival (OS)	Up to approximately 4.5 years	Overall Survival (OS) is defined as the time from date of first dose until death from any cause.
Number of Participants Who Discontinued Study Medication Due to an AE	Up to approximately 4.5 years	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.
Progression-free Survival (PFS)	Up to approximately 4.5 years	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.
Clinical Benefit Ratio (CBR)	Up to approximately 4.5 years	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.
Disease Control Rate (DCR)	Up to approximately 4.5 years	Disease Control Rate (DCR) is defined as the percentage of participants who achieved CR, PR, or SD per RECIST 1.1 by BICR.
Number of Participants Who Experienced One or More Adverse Events (AEs)	Up to approximately 4.5 years	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.

Trial Locations

Locations (56)

Comprehensive Cancer Centers of Nevada ( Site 0010); 🇺🇸 Las Vegas, Nevada, United States

Chernihiv Medical Center of Modern Oncology ( Site 0509); 🇺🇦 Chernihiv, Chernihivska Oblast, Ukraine

Russian Scientific Center of Radiology-Russian Scientific Center of Radiology ( Site 0602); 🇷🇺 Moscow, Moskva, Russian Federation

Cherkasy Regional Oncology Dispensary ( Site 0504); 🇺🇦 Cherkassy, Cherkaska Oblast, Ukraine

Szpital Kliniczny im. Przemienienia Panskiego Uniwersytetu M-chemotherapy department ( Site 0800); 🇵🇱 Poznań, Wielkopolskie, Poland

Volga District Medical Center-Urology Department ( Site 0604); 🇷🇺 Nizhny Novgorod, Nizhegorodskaya Oblast, Russian Federation

Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Okta-Klinikai Onkológiai és Sugárterápiás C; 🇭🇺 Miskolc, Borsod-Abauj-Zemplen, Hungary

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie (; 🇵🇱 Warszawa, Mazowieckie, Poland

Georgetown University Medical Center ( Site 0001); 🇺🇸 Washington, District of Columbia, United States

Istanbul Universitesi Cerrahpasa ( Site 1104); 🇹🇷 Istanbul- Fatih, Istanbul, Turkey

Institut de cancérologie Strasbourg Europe (ICANS) ( Site 1007); 🇫🇷 Strasbourg, Alsace, France

Jász-Nagykun-Szolnok Megyei Hetényi Géza Kórház-Onkologiai Kozpont ( Site 0303); 🇭🇺 Szolnok, Jasz-Nagykun-Szolnok, Hungary

St. Vincent Frontier Cancer Center ( Site 0004); 🇺🇸 Billings, Montana, United States

Dnepropetrovsk Regional Clinical Hospital Mechnikov-Department of urology ( Site 0508); 🇺🇦 Dnipro, Dnipropetrovska Oblast, Ukraine

Centre François Baclesse ( Site 1000); 🇫🇷 Caen, Calvados, France

Gustave Roussy ( Site 1002); 🇫🇷 Villejuif, Val-de-Marne, France

Tallaght University Hospital ( Site 1600); 🇮🇪 Dublin, Ireland

Fondazione Policlinico Universitario Agostino Gemelli-Medical Oncology ( Site 0901); 🇮🇹 Roma, Lazio, Italy

Luxmed Onkologia sp. z o. o. ( Site 0802); 🇵🇱 Warszawa, Mazowieckie, Poland

Nizhegorodsky Regional Oncology Dispensary, Branch #2-chemotherapy ( Site 0605); 🇷🇺 Nizhniy Novgorod, Nizhegorodskaya Oblast, Russian Federation

SHBI Leningrad Regional Clinical Oncology Dispensary-Clinical Trials Department ( Site 0607); 🇷🇺 Sankt-Peterburg, Russian Federation

Seattle Cancer Care Alliance ( Site 0014); 🇺🇸 Seattle, Washington, United States

BC Cancer Vancouver-Clinical Trials Unit ( Site 1500); 🇨🇦 Vancouver, British Columbia, Canada

Asan Medical Center-Department of Oncology ( Site 1300); 🇰🇷 Seoul, Korea, Republic of

Hospital Universitario Ramón y Cajal-Medical Oncology ( Site 0200); 🇪🇸 Madrid, Madrid, Comunidad De, Spain

Debreceni Egyetem Klinikai Kozpont-Onkológiai Klinika ( Site 0300); 🇭🇺 Debrecen, Hungary

Azienda Ospedaliera Santa Maria Terni-SC Oncologia ( Site 0900); 🇮🇹 Terni, Italy

Severance Hospital, Yonsei University Health System-Medical oncology ( Site 1302); 🇰🇷 Seoul, Korea, Republic of

Országos Onkológiai Intézet-Urogenital Tumors Department and Clinical Pharmacology ( Site 0304); 🇭🇺 Budapest, Pest, Hungary

centre hospitalier lyon sud ( Site 1003); 🇫🇷 Pierre-Bénite, Rhone, France

Calvary Mater Newcastle ( Site 0403); 🇦🇺 Waratah, New South Wales, Australia

Ashford Cancer Centre Research ( Site 0404); 🇦🇺 Kurralta Park, South Australia, Australia

Monash Health ( Site 0400); 🇦🇺 Clayton, Victoria, Australia

CHU de Quebec - Université Laval - Hotel Dieu de Quebec ( Site 1502); 🇨🇦 Québec, Quebec, Canada

Fox Chase Cancer Center ( Site 0011); 🇺🇸 Philadelphia, Pennsylvania, United States

Fiona Stanley Hospital ( Site 0402); 🇦🇺 Murdoch, Western Australia, Australia

Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 0903); 🇮🇹 Milan, Lombardia, Italy

Hacettepe Universitesi-oncology hospital ( Site 1101); 🇹🇷 Ankara, Turkey

Samsung Medical Center ( Site 1301); 🇰🇷 Seoul, Korea, Republic of

Hospital Universitari Vall d'Hebron-Departamento de Oncologia- VHIO ( Site 0201); 🇪🇸 Barcelona, Spain

Fundación Instituto Valenciano de Oncología-Oncologico ( Site 0202); 🇪🇸 Valencia, Valenciana, Comunitat, Spain

Ege University Medicine of Faculty ( Site 1102); 🇹🇷 Bornova, Izmir, Turkey

Ankara University Hospital Cebeci ( Site 1105); 🇹🇷 Ankara, Turkey

Göztepe Prof. Dr. Süleyman Yalçın Şehir Hastanesi-oncology ( Site 1103); 🇹🇷 Istanbul, Turkey

Centre de Cancérologie du Grand Montpellier ( Site 1005); 🇫🇷 Montpellier, Languedoc-Roussillon, France

The Christie ( Site 1205); 🇬🇧 Manchester, United Kingdom

Vanderbilt University Medical Center ( Site 0008); 🇺🇸 Nashville, Tennessee, United States

MEDICAL COLLEGE OF WISCONSIN ( Site 0006); 🇺🇸 Milwaukee, Wisconsin, United States

Sunnybrook Health Sciences Centre ( Site 1501); 🇨🇦 Toronto, Ontario, Canada

Princess Margaret Cancer Centre ( Site 1504); 🇨🇦 Toronto, Ontario, Canada

Memorial Sloan Kettering Cancer Center ( Site 0015); 🇺🇸 New York, New York, United States

Macquarie University-MQ Health Clinical Trials Unit ( Site 0405); 🇦🇺 Macquarie Park, New South Wales, Australia

Royal Brisbane and Women's Hospital-Medical Oncology Clinical Trials Unit, Cancer Care Services ( Si; 🇦🇺 Brisbane, Queensland, Australia

Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Borgo Roma-Oncology Unit ( Site 0902); 🇮🇹 Verona, Veneto, Italy

CNPE "Regional Center of Oncology"-oncourology department ( Site 0502); 🇺🇦 Kharkiv, Kharkivska Oblast, Ukraine

Cambridge University Hospital ( Site 1200); 🇬🇧 Cambridge, England, United Kingdom