Clinical Trials /

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

NCT04704219

Description:

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.

Related Conditions:
  • Non-Clear Cell Renal Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: 3475-B61
  • SECONDARY ID: MK-3475-B61
  • SECONDARY ID: 2020-004087-26
  • NCT ID: NCT04704219

Conditions

  • Renal Cell Carcinoma

Interventions

DrugSynonymsArms
PembrolizumabKEYTRUDA®, MK-3475Pembrolizumab + Lenvatinib
LenvatinibLENVIMA®, Kisplyx, MK-7902, E7080Pembrolizumab + Lenvatinib

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
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.
  • Pembrolizumab
  • Lenvatinib

Eligibility Criteria

        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 5 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 (non-infectious) pneumonitis that required steroids or has current
             pneumonitis.

         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.
      
Maximum Eligible Age:120 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:Up to approximately 2 years
Safety Issue:
Description: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

Measure:Duration of Response (DOR)
Time Frame:Up to approximately 2 years
Safety Issue:
Description: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.
Measure:Progression-free Survival (PFS)
Time Frame:Up to approximately 2 years
Safety Issue:
Description: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.
Measure:Overall Survival (OS)
Time Frame:Up to approximately 2 years
Safety Issue:
Description:Overall Survival (OS) is defined as the time from date of first dose until death from any cause.
Measure:Clinical Benefit Ratio (CBR)
Time Frame:Up to approximately 2 years
Safety Issue:
Description: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.
Measure:Disease Control Rate (DCR)
Time Frame:Up to approximately 2 years
Safety Issue:
Description:Disease Control Rate (DCR) is defined as the percentage of participants who achieved CR, PR, or SD per RECIST 1.1 by BICR.
Measure:Number of Participants Who Experienced One or More Adverse Events (AEs)
Time Frame:Up to approximately 2 years
Safety Issue:
Description: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.
Measure:Number of Participants Who Discontinued Study Medication Due to an AE
Time Frame:Up to approximately 2 years
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Merck Sharp & Dohme Corp.

Trial Keywords

  • Programmed Cell Death-1 (PD1, PD-1)
  • Programmed Death-Ligand 1 (PDL1, PD-L1)
  • Pembrolizumab
  • Lenvatinib

Last Updated

July 16, 2021