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

• ClinicalTrials.gov Identifier: NCT04704219
• Recruitment Status: Active, not recruiting
• First Posted: January 11, 2021
• Last Update Posted: January 16, 2024
• Sponsor: Merck Sharp & Dohme LLC
• Collaborator: Eisai Inc.
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

Tracking Information

• First Submitted Date: January 7, 2021
• First Posted Date: January 11, 2021
• Last Update Posted Date: January 16, 2024
• Actual Study Start Date: February 23, 2021
• Estimated Primary Completion Date: August 16, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 19, 2021)

Objective Response Rate (ORR) [ Time Frame: 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).

Original Primary Outcome Measures (submitted: January 7, 2021)

Objective Response Rate (ORR) [ Time Frame: Up to approximately 2 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).

Current Secondary Outcome Measures (submitted: September 19, 2021)

• Duration of Response (DOR) [ Time Frame: 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.
• Progression-free Survival (PFS) [ Time Frame: 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.
• Overall Survival (OS) [ Time Frame: Up to approximately 4.5 years ]
  Overall Survival (OS) is defined as the time from date of first dose until death from any cause.
• Clinical Benefit Ratio (CBR) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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.
• Number of Participants Who Discontinued Study Medication Due to an AE [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: January 7, 2021)

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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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)
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: 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.
  Other Names:

  • KEYTRUDA®
  • MK-3475
• Drug: Lenvatinib
  Lenvatinib 20 mg, daily (QD), oral, until progressive disease or discontinuation.
  Other Names:

  • LENVIMA®
  • Kisplyx
  • MK-7902
  • E7080

Study Arms

Experimental: Pembrolizumab + 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.

Interventions:

• Biological: Pembrolizumab
• Drug: Lenvatinib

• Publications *: 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: January 7, 2021): 152
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 22, 2025
• Estimated Primary Completion Date: August 16, 2024 (Final data collection date for primary outcome measure)

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 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 120 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, France, Hungary, Ireland, Italy, Korea, Republic of, Poland, Russian Federation, Spain, Turkey, Ukraine, United Kingdom, United States

Administrative Information

• NCT Number: NCT04704219
• Other Study ID Numbers: 3475-B61; MK-3475-B61 ( Other Identifier: Merck ); 2020-004087-26 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

• Current Responsible Party: Merck Sharp & Dohme LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Merck Sharp & Dohme LLC
• Original Study Sponsor: Same as current
• Collaborators: Eisai Inc.

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme LLC

• PRS Account: Merck Sharp & Dohme LLC
• Verification Date: January 2024