Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04704219




Registration number
NCT04704219
Ethics application status
Date submitted
7/01/2021
Date registered
11/01/2021
Date last updated
16/01/2024

Titles & IDs
Public title
Pembrolizumab Plus Lenvatinib for First-line Advanced/Metastatic Non-clear Cell Renal Cell Carcinoma (1L nccRCC) (MK-3475-B61)
Scientific 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)
Secondary ID [1] 0 0
MK-3475-B61
Secondary ID [2] 0 0
3475-B61
Universal Trial Number (UTN)
Trial acronym
KEYNOTE-B61
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Renal Cell Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Pembrolizumab
Treatment: Drugs - Lenvatinib

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.


Other interventions: Pembrolizumab
Pembrolizumab 400 mg, every 6 weeks (Q6W) intravenous (IV) up to 18 infusions or up to progressive disease or discontinuation.

Treatment: Drugs: Lenvatinib
Lenvatinib 20 mg, daily (QD), oral, until progressive disease or discontinuation.
Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective Response Rate (ORR)
Timepoint [1] 0 0
Up to approximately 3 years
Secondary outcome [1] 0 0
Duration of Response (DOR)
Timepoint [1] 0 0
Up to approximately 4.5 years
Secondary outcome [2] 0 0
Progression-free Survival (PFS)
Timepoint [2] 0 0
Up to approximately 4.5 years
Secondary outcome [3] 0 0
Overall Survival (OS)
Timepoint [3] 0 0
Up to approximately 4.5 years
Secondary outcome [4] 0 0
Clinical Benefit Ratio (CBR)
Timepoint [4] 0 0
Up to approximately 4.5 years
Secondary outcome [5] 0 0
Disease Control Rate (DCR)
Timepoint [5] 0 0
Up to approximately 4.5 years
Secondary outcome [6] 0 0
Number of Participants Who Experienced One or More Adverse Events (AEs)
Timepoint [6] 0 0
Up to approximately 4.5 years
Secondary outcome [7] 0 0
Number of Participants Who Discontinued Study Medication Due to an AE
Timepoint [7] 0 0
Up to approximately 4.5 years

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
120 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
23/02/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
22/10/2025
Actual
Sample size
Target
152
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Macquarie University-MQ Health Clinical Trials Unit ( Site 0405) - Macquarie Park
Recruitment hospital [2] 0 0
Calvary Mater Newcastle ( Site 0403) - Waratah
Recruitment hospital [3] 0 0
Royal Brisbane and Women's Hospital-Medical Oncology Clinical Trials Unit, Cancer Care Services ( Si - Brisbane
Recruitment hospital [4] 0 0
Ashford Cancer Centre Research ( Site 0404) - Kurralta Park
Recruitment hospital [5] 0 0
Monash Health ( Site 0400) - Clayton
Recruitment hospital [6] 0 0
Fiona Stanley Hospital ( Site 0402) - Murdoch
Recruitment postcode(s) [1] 0 0
2109 - Macquarie Park
Recruitment postcode(s) [2] 0 0
2298 - Waratah
Recruitment postcode(s) [3] 0 0
4029 - Brisbane
Recruitment postcode(s) [4] 0 0
5037 - Kurralta Park
Recruitment postcode(s) [5] 0 0
3168 - Clayton
Recruitment postcode(s) [6] 0 0
6150 - Murdoch
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
District of Columbia
Country [2] 0 0
United States of America
State/province [2] 0 0
Montana
Country [3] 0 0
United States of America
State/province [3] 0 0
Nevada
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
Pennsylvania
Country [6] 0 0
United States of America
State/province [6] 0 0
Tennessee
Country [7] 0 0
United States of America
State/province [7] 0 0
Washington
Country [8] 0 0
United States of America
State/province [8] 0 0
Wisconsin
Country [9] 0 0
Canada
State/province [9] 0 0
British Columbia
Country [10] 0 0
Canada
State/province [10] 0 0
Ontario
Country [11] 0 0
Canada
State/province [11] 0 0
Quebec
Country [12] 0 0
France
State/province [12] 0 0
Alsace
Country [13] 0 0
France
State/province [13] 0 0
Calvados
Country [14] 0 0
France
State/province [14] 0 0
Languedoc-Roussillon
Country [15] 0 0
France
State/province [15] 0 0
Rhone
Country [16] 0 0
France
State/province [16] 0 0
Val-de-Marne
Country [17] 0 0
Hungary
State/province [17] 0 0
Borsod-Abauj-Zemplen
Country [18] 0 0
Hungary
State/province [18] 0 0
Jasz-Nagykun-Szolnok
Country [19] 0 0
Hungary
State/province [19] 0 0
Pest
Country [20] 0 0
Hungary
State/province [20] 0 0
Debrecen
Country [21] 0 0
Ireland
State/province [21] 0 0
Dublin
Country [22] 0 0
Italy
State/province [22] 0 0
Lazio
Country [23] 0 0
Italy
State/province [23] 0 0
Lombardia
Country [24] 0 0
Italy
State/province [24] 0 0
Veneto
Country [25] 0 0
Italy
State/province [25] 0 0
Terni
Country [26] 0 0
Korea, Republic of
State/province [26] 0 0
Seoul
Country [27] 0 0
Poland
State/province [27] 0 0
Mazowieckie
Country [28] 0 0
Poland
State/province [28] 0 0
Wielkopolskie
Country [29] 0 0
Russian Federation
State/province [29] 0 0
Moskva
Country [30] 0 0
Russian Federation
State/province [30] 0 0
Nizhegorodskaya Oblast
Country [31] 0 0
Russian Federation
State/province [31] 0 0
Sankt-Peterburg
Country [32] 0 0
Spain
State/province [32] 0 0
Madrid, Comunidad De
Country [33] 0 0
Spain
State/province [33] 0 0
Valenciana, Comunitat
Country [34] 0 0
Spain
State/province [34] 0 0
Barcelona
Country [35] 0 0
Turkey
State/province [35] 0 0
Istanbul
Country [36] 0 0
Turkey
State/province [36] 0 0
Izmir
Country [37] 0 0
Turkey
State/province [37] 0 0
Ankara
Country [38] 0 0
Ukraine
State/province [38] 0 0
Cherkaska Oblast
Country [39] 0 0
Ukraine
State/province [39] 0 0
Chernihivska Oblast
Country [40] 0 0
Ukraine
State/province [40] 0 0
Dnipropetrovska Oblast
Country [41] 0 0
Ukraine
State/province [41] 0 0
Kharkivska Oblast
Country [42] 0 0
United Kingdom
State/province [42] 0 0
England
Country [43] 0 0
United Kingdom
State/province [43] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Merck Sharp & Dohme LLC
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Eisai Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04704219
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04704219