TriangleNCT04704219 · CITED IN SOURCE DOCUMENTS
Pembrolizumab Plus Lenvatinib for First-line Advanced/Metastatic Non-clear Cell Renal Cell Carcinoma (1L nccRCC) (MK-3475-B61)
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE2
- Status at capture
- COMPLETED
- Registry last update
- 2025-12-03
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.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Objective Response Rate (ORR)
Duration of Response (DOR)
Progression Free Survival (PFS)
Overall Survival (OS)
Clinical Benefit Rate (CBR)
Disease Control Rate (DCR)
Number of Participants With One or More Adverse Events (AEs)
Number of Participants Who Discontinued From Study Treatment Due to an AE
Adverse events
Limitations, agreements, and source contact
Who could take part
- 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.
- healthy Volunteers
- false
- maximum Age
- 120 Years
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- 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.
- intervention Names
- Biological: Pembrolizumab
- Drug: Lenvatinib
- label
- Pembrolizumab + Lenvatinib
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- Pembrolizumab + Lenvatinib
- description
- Pembrolizumab 400 mg, every 6 weeks (Q6W) intravenous (IV) up to 18 infusions or up to progressive disease or discontinuation.
- name
- Pembrolizumab
- other Names
- KEYTRUDA®
- MK-3475
- type
- BIOLOGICAL
- arm Group Labels
- Pembrolizumab + Lenvatinib
- description
- Lenvatinib 20 mg, daily (QD), oral, until progressive disease or discontinuation.
- name
- Lenvatinib
- other Names
- LENVIMA®
- Kisplyx
- MK-7902
- E7080
- type
- DRUG
Study design
- allocation
- NA
- intervention Model
- SINGLE_GROUP
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 160
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- 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.
- measure
- Objective Response Rate (ORR)
- time Frame
- Up to approximately 47 months
- secondary Outcomes
- description
- 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.
- measure
- Duration of Response (DOR)
- time Frame
- Up to approximately 47 months
- description
- 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.
- measure
- Progression Free Survival (PFS)
- time Frame
- Up to approximately 47 months
- description
- 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.
- measure
- Overall Survival (OS)
- time Frame
- Up to approximately 47 months
- description
- 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).
- measure
- Clinical Benefit Rate (CBR)
- time Frame
- Up to approximately 47 months
- description
- 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.
- measure
- Disease Control Rate (DCR)
- time Frame
- Up to approximately 47 months
- description
- 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.
- measure
- Number of Participants With One or More Adverse Events (AEs)
- time Frame
- Up to approximately 56 months
- description
- 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.
- measure
- Number of Participants Who Discontinued From Study Treatment Due to an AE
- time Frame
- Up to approximately 56 months
Full study description
- 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.
Source references
- 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.
- pmid
- 37451291
- type
- RESULT
- citation
- 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
- type
- RESULT
- see Also Links
- label
- Merck Clinical Trials Information
Source notices and limitations
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Preserved source evidence · Not medical advice