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Substudy 03A: A Study of Immune and Targeted Combination Therapies in Participants With First Line (1L) Renal Cell Carcinoma (MK-3475-03A)

Primary Purpose

Carcinoma, Renal Cell

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Pembrolizumab
Favezelimab/Pembrolizumab
Belzutifan
Lenvatinib
Pembrolizumab/Quavonlimab
Vibostolimab/Pembrolizumab
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Carcinoma, Renal Cell focused on measuring receptor tyrosine kinase inhibitor, programmed cell death 1 (PD-1, PD1), programmed cell death ligand 1 (PD-L1, PDL1)

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Has a histologically confirmed diagnosis of locally advanced/metastatic ccRCC
  • Has received no prior systemic therapy for advanced RCC; prior neoadjuvant/adjuvant therapy for RCC is acceptable if completed ≥12 months before randomization/allocation.
  • Is able to swallow oral medication
  • Has adequate organ function
  • Participants receiving bone resorptive therapy must have therapy initiated at least 2 weeks before randomization/allocation
  • Has resolution of toxic effects of the most recent prior therapy to ≤Grade 1
  • Has adequately controlled blood pressure (BP ≤150/90 mm Hg) with no change in hypertensive medications within 1 week before randomization/allocation
  • Male participants are abstinent from heterosexual intercourse or agree to use contraception during treatment with and for at least 7 days after the last dose of lenvatinib and /or belzutifan; 7 days after lenvatinib and/or belzutifan is stopped, if the participant is only receiving pembrolizumab, pembrolizumab/quavonlimab, favezelimab/pembrolizumab or a combination of the aforementioned drugs, no contraception is needed
  • Female participants must not be pregnant and not be a woman of childbearing potential (WOCBP) or is a WOCBP abstinent from heterosexual intercourse or using contraception during the intervention period and for at least 120 days after the last dose of pembrolizumab, pembrolizumab/quavonlimab, favezelimab/pembrolizumab for 30 days after the last dose of lenvatinib or belzutifan, whichever occurs last and must abstain from breastfeeding during the study intervention period and for at least 120 days after study intervention

Exclusion Criteria:

  • Has urine protein ≥1 g/24 hours and has any of the following: (a) a pulse oximeter reading <92% at rest, or (b) requires intermittent supplemental oxygen, or (c) requires chronic supplemental oxygen (d) active hemoptysis within 3 weeks prior to the first dose of study intervention
  • Has clinically significant cardiovascular disease within 12 months from the first dose of study intervention administration
  • Has had major surgery within 3 weeks before first dose of study interventions
  • Has a history of lung disease
  • Has a history of inflammatory bowel disease
  • Has preexisting gastrointestinal (GI) or non-GI fistula
  • Has malabsorption due to prior GI surgery or disease
  • Has received prior radiotherapy within 2 weeks of start of study intervention
  • Has received a live or live attenuated vaccine within 30 days before the first dose of study drug; killed vaccines are allowed
  • Has received more than 4 previous systemic anticancer treatment regimens
  • Has a diagnosis of immunodeficiency or is receiving any form of immunosuppressive therapy within 7 days prior to the first dose of study intervention
  • Has known additional malignancy that is progressing or has required active treatment within the past 3 years
  • Has known central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Has an active autoimmune disease that has required systemic treatment in the past 2 years; replacement therapy is not considered a form of systemic treatment and is allowed
  • Has an active infection requiring systemic therapy
  • Has a known history of human immunodeficiency virus (HIV) infection
  • Has a known history of Hepatitis B
  • Has had an allogenic tissue/solid organ transplant

Sites / Locations

  • University of California at San Francisco ( Site 1008)Recruiting
  • Yale-New Haven Hospital-Yale Cancer Center ( Site 1011)Recruiting
  • University of Chicago ( Site 1013)Recruiting
  • University of Iowa ( Site 1012)Recruiting
  • Henry Ford Health System ( Site 1014)
  • Laura and Isaac Perlmutter Cancer Center ( Site 1016)Recruiting
  • Memorial Sloan Kettering Cancer Center ( Site 1002)Recruiting
  • Duke Cancer Institute ( Site 1015)Recruiting
  • UPMC Cancer Center/Hillman Cancer Center ( Site 1017)Recruiting
  • UTSW Medical Center ( Site 1003)Recruiting
  • Western Sydney Local Health District ( Site 1601)Recruiting
  • St George Hospital ( Site 1602)Recruiting
  • Royal Brisbane and Women s Hospital ( Site 1603)Recruiting
  • Austin Health ( Site 1600)Recruiting
  • Princess Margaret Cancer Centre ( Site 1101)Recruiting
  • Jewish General Hospital ( Site 1100)Recruiting
  • James Lind Centro de Investigación del Cáncer ( Site 2108)Recruiting
  • CIDO SpA-Oncology ( Site 2106)Recruiting
  • FALP-UIDO ( Site 2100)Recruiting
  • Oncovida ( Site 2107)Recruiting
  • Bradfordhill-Clinical Area ( Site 2101)Recruiting
  • ONCOCENTRO APYS-ACEREY ( Site 2103)Recruiting
  • Sociedad De Oncologia Y Hematologia Del Cesar-Oncology ( Site 1905)Recruiting
  • Oncomédica S.A.S ( Site 1904)Recruiting
  • Clinica Colsanitas S.A, Sede Clínica Universitaria Colombia-Center Investigator ( Site 1900)Recruiting
  • Fundacion Valle del Lili- CIC ( Site 1901)Recruiting
  • Institut De Cancerologie De Lorraine ( Site 1204)Recruiting
  • Institut de cancérologie Strasbourg Europe (ICANS) ( Site 1203)Recruiting
  • Institut Claudius Regaud ( Site 1200)Recruiting
  • Gustave Roussy ( Site 1202)Recruiting
  • Országos Onkológiai Intézet-Urogenitális Tumorok és Klinikai Farmakológiai Osztály ( Site 2301)Recruiting
  • Rambam MC ( Site 1500)Recruiting
  • Hadassah Medical Center-Oncology ( Site 1504)Recruiting
  • Rabin Medical Center ( Site 1502)Recruiting
  • Sheba Medical Center - Oncology Division ( Site 1501)Recruiting
  • Sourasky Medical Center ( Site 1503)Recruiting
  • Asan Medical Center ( Site 1800)Recruiting
  • Severance Hospital ( Site 1802)Recruiting
  • Samsung Medical Center ( Site 1801)Recruiting
  • Nederlands Kanker Instituut - Antoni van Leeuwenhoek (NKI-AVL)-medical oncology ( Site 2402)Recruiting
  • Erasmus Medisch Centrum ( Site 2401)Recruiting
  • Auckland City Hospital ( Site 1700)Recruiting
  • Centrum Onkologii im. Prof. Franciszka Lukaszczyka-Ambulatorium Chemioterapii ( Site 2201)Recruiting
  • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Oddzial Badan Wczesnych Faz ( Site 2200Recruiting
  • Uniwersyteckie Centrum Kliniczne-Early Clinical Trials Unit ( Site 2202)Recruiting
  • Hospital Universitari Vall d Hebron ( Site 1300)Recruiting
  • Hospital Universitario Ramon y Cajal ( Site 1301)Recruiting
  • Southampton General Hospital ( Site 1403)Recruiting
  • The Beatson West of Scotland Cancer Centre ( Site 1405)Recruiting
  • Royal Preston Hospital ( Site 1406)
  • Leicester Royal Infirmary ( Site 1408)Recruiting
  • Barts Health NHS Trust ( Site 1401)Recruiting
  • Western General Hospital ( Site 1402)Recruiting
  • Velindre Cancer Centre Hospital ( Site 1407)Recruiting
  • The Christie NHS Foundation Trust ( Site 1400)Recruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Coformulation Pembrolizumab/Quavonlimab + Lenvatinib

Coformulation Favezelimab/Pembrolizumab+ Lenvatinib

Pembrolizumab + Belzutifan + Lenvatinib

Pembrolizumab + Lenvatinib

Coformulation Vibostolimab/Pembrolizumab+Belzutifan

Arm Description

Participants will receive pembrolizumab/quavonlimab (coformulation of pembrolizumab 400 mg and quavonlimab 25 mg) PLUS lenvatinib 20 mg. Pembrolizumab/quavonlimab will be administered intravenously (IV) once every 6 weeks (Q6W) for up to 17 administrations (up to ~2 years). Lenvatinib will be administered orally once-daily (QD) until progressive disease or discontinuation.

Participants will receive favezelimab/pembrolizumab (coformulation of favezelimab 800 mg and pembrolizumab 200 mg) PLUS lenvatinib 20 mg. Favezelimab/Pembrolizumab will be administered IV once every 3 weeks (Q3W) for up to 35 administrations (up to ~2 years). Lenvatinib will be administered orally QD until progressive disease or discontinuation.

Participants will receive pembrolizumab 400 mg PLUS belzutifan 120 mg PLUS lenvatinib 20 mg. Pembrolizumab will be administered IV Q6W for up to 17 administrations (up to ~2 years). Both belzutifan and lenvatinib will be administered orally QD until progressive disease or discontinuation.

Participants will receive pembrolizumab 400 mg PLUS lenvatinib 20 mg. Pembrolizumab will be administered IV Q6W for up to 17 administrations (up to ~ 2 years). Lenvatinib will be administered orally QD until progressive disease or discontinuation.

Participants will receive vibostolimab/pembrolizumab (coformulation of 200 mg vibostolimab and pembrolizumab 200 mg). Vibostolimab/pembrolizumab will be administered IV once every 3 weeks (Q3W) for up to 35 administrations (up to ~2 years). Belzutifan will be administered orally QD until progressive disease or discontinuation.

Outcomes

Primary Outcome Measures

Safety Lead-in Phase: Number of participants who experience one or more dose-limiting toxicities (DLTs)
DLTs are defined as one or more of the following toxicities: (1) grade (gr) 4 nonhematologic toxicity (2) gr 4 hematologic toxicity lasting >7 days OR gr 4 platelet count decreased of any duration OR gr 3 platelet count decreased if associated with bleeding (3) gr 3 nonhematologic toxicity except gr 3 fatigue (lasting ≤3 days), diarrhea, nausea, vomiting or rash without standard of care (4) gr 3 or 4 nonhematologic abnormality if medical intervention is required or if it leads to hospitalization or persists for >1 week (5) gr 3 or 4 febrile neutropenia (6) gr 3 or 4 alanine aminotransferase, aspartate aminotransferase and/or bilirubin laboratory value (7) treatment related adverse event (AE) causing study intervention discontinuation during the first 21 days (8) treatment related AE causing intervention administration delay for >14 days during the first 21 days (9) gr 5 toxicity. The number of participants who experience one or more DLTs in the safety lead-in phase will be presented.
Safety Lead-in Phase: Number of participants who experience one or more adverse events (AEs)
An AE is 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. The number of participants who experience one or more AEs in the safety lead-in phase will be presented.
Safety Lead-in Phase: Number of participants who discontinue study treatment due to an AE
An AE is 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. The number of participants who discontinue study treatment due to an AE in the safety lead-in phase will be presented.
Efficacy Phase: Number of participants who experience one or more DLTs
DLTs are defined as one or more of the following toxicities: (1) grade (gr) 4 nonhematologic toxicity (2) gr 4 hematologic toxicity lasting >7 days OR gr 4 platelet count decreased of any duration OR gr 3 platelet count decreased if associated with bleeding (3) gr 3 nonhematologic toxicity except gr 3 fatigue (lasting ≤3 days), diarrhea, nausea, vomiting or rash without standard of care (4) gr 3 or 4 nonhematologic abnormality if medical intervention is required or if it leads to hospitalization or persists for >1 week (5) gr 3 or 4 febrile neutropenia (6) gr 3 or 4 alanine aminotransferase, aspartate aminotransferase and/or bilirubin laboratory value (7) treatment related adverse event (AE) causing study intervention discontinuation during the first 21 days (8) treatment related AE causing intervention administration delay for >14 days during the first 21 days (9) gr 5 toxicity. The number of participants who experience one or more DLTs in the efficacy phase will be presented.
Efficacy Phase: Number of participants who experience one or more AEs
An AE is 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. The number of participants who experience one or more AEs in the efficacy phase will be presented.
Efficacy Phase: Number of participants who discontinue study treatment due to an AE
An AE is 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. The number of participants who discontinue study treatment due to an AE in the efficacy phase will be presented.
Efficacy Phase: Objective response rate (ORR)
ORR is defined as the percentage of participants in the analysis population 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, taking as reference the baseline sum of diameters). Responses are according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR).

Secondary Outcome Measures

Efficacy Phase: Duration of response (DOR)
For participants in the analysis population who demonstrate a confirmed CR (disappearance of all target lesions) or confirmed PR (at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters), DOR is defined as the time from first documented evidence of CR or PR until progressive disease or death due to any cause, whichever occurs first. Responses are according to RECIST 1.1 by BICR.
Efficacy Phase: Progression-free survival (PFS)
PFS is defined as the time from randomization to the first documented progressive disease or death due to any cause, whichever occurs first. Responses are according to RECIST 1.1 by BICR.
Efficacy Phase: Overall survival (OS)
OS is defined as the time from randomization to death due to any cause.
Efficacy Phase: Clinical benefit rate (CBR)
CBR is defined as the percentage of participants who have achieved CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters) or stable disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease) of ≥6 months. Responses are according to RECIST 1.1 by BICR.

Full Information

First Posted
November 10, 2020
Last Updated
October 18, 2023
Sponsor
Merck Sharp & Dohme LLC
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1. Study Identification

Unique Protocol Identification Number
NCT04626479
Brief Title
Substudy 03A: A Study of Immune and Targeted Combination Therapies in Participants With First Line (1L) Renal Cell Carcinoma (MK-3475-03A)
Official Title
A Phase 1b/2 Study of Immune and Targeted Combination Therapies in Participants With RCC (U03): Substudy 03A
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 16, 2020 (Actual)
Primary Completion Date
May 31, 2026 (Anticipated)
Study Completion Date
May 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Substudy 03A is part of a larger research study that is testing experimental treatments for renal cell carcinoma (RCC). The larger study is the umbrella study (U03). The goal of substudy 03A is to evaluate the safety and efficacy of experimental combinations of investigational agents in participants with advanced first line (1L) clear cell renal cell carcinoma (ccRCC). This substudy will have two phases: a safety lead-in phase and an efficacy phase. The safety lead-in phase will be used to demonstrate a tolerable safety profile for the combination of investigational agents. There will be no hypothesis testing in this study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Renal Cell
Keywords
receptor tyrosine kinase inhibitor, programmed cell death 1 (PD-1, PD1), programmed cell death ligand 1 (PD-L1, PDL1)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
400 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Coformulation Pembrolizumab/Quavonlimab + Lenvatinib
Arm Type
Experimental
Arm Description
Participants will receive pembrolizumab/quavonlimab (coformulation of pembrolizumab 400 mg and quavonlimab 25 mg) PLUS lenvatinib 20 mg. Pembrolizumab/quavonlimab will be administered intravenously (IV) once every 6 weeks (Q6W) for up to 17 administrations (up to ~2 years). Lenvatinib will be administered orally once-daily (QD) until progressive disease or discontinuation.
Arm Title
Coformulation Favezelimab/Pembrolizumab+ Lenvatinib
Arm Type
Experimental
Arm Description
Participants will receive favezelimab/pembrolizumab (coformulation of favezelimab 800 mg and pembrolizumab 200 mg) PLUS lenvatinib 20 mg. Favezelimab/Pembrolizumab will be administered IV once every 3 weeks (Q3W) for up to 35 administrations (up to ~2 years). Lenvatinib will be administered orally QD until progressive disease or discontinuation.
Arm Title
Pembrolizumab + Belzutifan + Lenvatinib
Arm Type
Experimental
Arm Description
Participants will receive pembrolizumab 400 mg PLUS belzutifan 120 mg PLUS lenvatinib 20 mg. Pembrolizumab will be administered IV Q6W for up to 17 administrations (up to ~2 years). Both belzutifan and lenvatinib will be administered orally QD until progressive disease or discontinuation.
Arm Title
Pembrolizumab + Lenvatinib
Arm Type
Experimental
Arm Description
Participants will receive pembrolizumab 400 mg PLUS lenvatinib 20 mg. Pembrolizumab will be administered IV Q6W for up to 17 administrations (up to ~ 2 years). Lenvatinib will be administered orally QD until progressive disease or discontinuation.
Arm Title
Coformulation Vibostolimab/Pembrolizumab+Belzutifan
Arm Type
Experimental
Arm Description
Participants will receive vibostolimab/pembrolizumab (coformulation of 200 mg vibostolimab and pembrolizumab 200 mg). Vibostolimab/pembrolizumab will be administered IV once every 3 weeks (Q3W) for up to 35 administrations (up to ~2 years). Belzutifan will be administered orally QD until progressive disease or discontinuation.
Intervention Type
Biological
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
MK-3475, KEYTRUDA®
Intervention Description
Administered via IV infusion at a dose of 400 mg Q6W
Intervention Type
Biological
Intervention Name(s)
Favezelimab/Pembrolizumab
Other Intervention Name(s)
MK-4280A
Intervention Description
Administered via IV infusion at a dose of 800 mg/200 mg Q3W
Intervention Type
Drug
Intervention Name(s)
Belzutifan
Other Intervention Name(s)
MK-6482, WELIREG™
Intervention Description
Administered via oral tablet at a dose of 120 mg QD
Intervention Type
Drug
Intervention Name(s)
Lenvatinib
Other Intervention Name(s)
MK-7902, E7080, LENVIMA®
Intervention Description
Administered via oral capsule at a dose of 20 mg QD
Intervention Type
Biological
Intervention Name(s)
Pembrolizumab/Quavonlimab
Other Intervention Name(s)
MK-1308A
Intervention Description
Administered via IV infusion at a dose of 400 mg/25 mg Q6W
Intervention Type
Drug
Intervention Name(s)
Vibostolimab/Pembrolizumab
Other Intervention Name(s)
MK-7684A
Intervention Description
Administered via IV infusion at a dose of 200 mg/200 mg Q6W
Primary Outcome Measure Information:
Title
Safety Lead-in Phase: Number of participants who experience one or more dose-limiting toxicities (DLTs)
Description
DLTs are defined as one or more of the following toxicities: (1) grade (gr) 4 nonhematologic toxicity (2) gr 4 hematologic toxicity lasting >7 days OR gr 4 platelet count decreased of any duration OR gr 3 platelet count decreased if associated with bleeding (3) gr 3 nonhematologic toxicity except gr 3 fatigue (lasting ≤3 days), diarrhea, nausea, vomiting or rash without standard of care (4) gr 3 or 4 nonhematologic abnormality if medical intervention is required or if it leads to hospitalization or persists for >1 week (5) gr 3 or 4 febrile neutropenia (6) gr 3 or 4 alanine aminotransferase, aspartate aminotransferase and/or bilirubin laboratory value (7) treatment related adverse event (AE) causing study intervention discontinuation during the first 21 days (8) treatment related AE causing intervention administration delay for >14 days during the first 21 days (9) gr 5 toxicity. The number of participants who experience one or more DLTs in the safety lead-in phase will be presented.
Time Frame
Up to ~21 days
Title
Safety Lead-in Phase: Number of participants who experience one or more adverse events (AEs)
Description
An AE is 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. The number of participants who experience one or more AEs in the safety lead-in phase will be presented.
Time Frame
Up to ~21 days
Title
Safety Lead-in Phase: Number of participants who discontinue study treatment due to an AE
Description
An AE is 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. The number of participants who discontinue study treatment due to an AE in the safety lead-in phase will be presented.
Time Frame
Up to ~21 days
Title
Efficacy Phase: Number of participants who experience one or more DLTs
Description
DLTs are defined as one or more of the following toxicities: (1) grade (gr) 4 nonhematologic toxicity (2) gr 4 hematologic toxicity lasting >7 days OR gr 4 platelet count decreased of any duration OR gr 3 platelet count decreased if associated with bleeding (3) gr 3 nonhematologic toxicity except gr 3 fatigue (lasting ≤3 days), diarrhea, nausea, vomiting or rash without standard of care (4) gr 3 or 4 nonhematologic abnormality if medical intervention is required or if it leads to hospitalization or persists for >1 week (5) gr 3 or 4 febrile neutropenia (6) gr 3 or 4 alanine aminotransferase, aspartate aminotransferase and/or bilirubin laboratory value (7) treatment related adverse event (AE) causing study intervention discontinuation during the first 21 days (8) treatment related AE causing intervention administration delay for >14 days during the first 21 days (9) gr 5 toxicity. The number of participants who experience one or more DLTs in the efficacy phase will be presented.
Time Frame
Up to ~21 days
Title
Efficacy Phase: Number of participants who experience one or more AEs
Description
An AE is 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. The number of participants who experience one or more AEs in the efficacy phase will be presented.
Time Frame
Up to ~43 months
Title
Efficacy Phase: Number of participants who discontinue study treatment due to an AE
Description
An AE is 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. The number of participants who discontinue study treatment due to an AE in the efficacy phase will be presented.
Time Frame
Up to ~43 months
Title
Efficacy Phase: Objective response rate (ORR)
Description
ORR is defined as the percentage of participants in the analysis population 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, taking as reference the baseline sum of diameters). Responses are according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR).
Time Frame
Up to ~43 months
Secondary Outcome Measure Information:
Title
Efficacy Phase: Duration of response (DOR)
Description
For participants in the analysis population who demonstrate a confirmed CR (disappearance of all target lesions) or confirmed PR (at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters), DOR is defined as the time from first documented evidence of CR or PR until progressive disease or death due to any cause, whichever occurs first. Responses are according to RECIST 1.1 by BICR.
Time Frame
Up to ~43 months
Title
Efficacy Phase: Progression-free survival (PFS)
Description
PFS is defined as the time from randomization to the first documented progressive disease or death due to any cause, whichever occurs first. Responses are according to RECIST 1.1 by BICR.
Time Frame
Up to ~43 months
Title
Efficacy Phase: Overall survival (OS)
Description
OS is defined as the time from randomization to death due to any cause.
Time Frame
Up to ~43 months
Title
Efficacy Phase: Clinical benefit rate (CBR)
Description
CBR is defined as the percentage of participants who have achieved CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters) or stable disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease) of ≥6 months. Responses are according to RECIST 1.1 by BICR.
Time Frame
Up to ~43 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Has a histologically confirmed diagnosis of locally advanced/metastatic ccRCC Has received no prior systemic therapy for advanced RCC; prior neoadjuvant/adjuvant therapy for RCC is acceptable if completed ≥12 months before randomization/allocation. Is able to swallow oral medication Has adequate organ function Participants receiving bone resorptive therapy must have therapy initiated at least 2 weeks before randomization/allocation Has resolution of toxic effects of the most recent prior therapy to ≤Grade 1 Has adequately controlled blood pressure (BP ≤150/90 mm Hg) with no change in hypertensive medications within 1 week before randomization/allocation Male participants are abstinent from heterosexual intercourse or agree to use contraception during treatment with and for at least 7 days after the last dose of lenvatinib and /or belzutifan; 7 days after lenvatinib and/or belzutifan is stopped, if the participant is only receiving pembrolizumab, pembrolizumab/quavonlimab, favezelimab/pembrolizumab or a combination of the aforementioned drugs, no contraception is needed Female participants must not be pregnant and not be a woman of childbearing potential (WOCBP) or is a WOCBP abstinent from heterosexual intercourse or using contraception during the intervention period and for at least 120 days after the last dose of pembrolizumab, pembrolizumab/quavonlimab, favezelimab/pembrolizumab for 30 days after the last dose of lenvatinib or belzutifan, whichever occurs last and must abstain from breastfeeding during the study intervention period and for at least 120 days after study intervention Exclusion Criteria: Has urine protein ≥1 g/24 hours and has any of the following: (a) a pulse oximeter reading <92% at rest, or (b) requires intermittent supplemental oxygen, or (c) requires chronic supplemental oxygen (d) active hemoptysis within 3 weeks prior to the first dose of study intervention Has clinically significant cardiovascular disease within 12 months from the first dose of study intervention administration Has had major surgery within 3 weeks before first dose of study interventions Has a history of lung disease Has a history of inflammatory bowel disease Has preexisting gastrointestinal (GI) or non-GI fistula Has malabsorption due to prior GI surgery or disease Has received prior radiotherapy within 2 weeks of start of study intervention Has received a live or live attenuated vaccine within 30 days before the first dose of study drug; killed vaccines are allowed Has received more than 4 previous systemic anticancer treatment regimens Has a diagnosis of immunodeficiency or is receiving any form of immunosuppressive therapy within 7 days prior to the first dose of study intervention Has known additional malignancy that is progressing or has required active treatment within the past 3 years Has known central nervous system (CNS) metastases and/or carcinomatous meningitis Has an active autoimmune disease that has required systemic treatment in the past 2 years; replacement therapy is not considered a form of systemic treatment and is allowed Has an active infection requiring systemic therapy Has a known history of human immunodeficiency virus (HIV) infection Has a known history of Hepatitis B Has had an allogenic tissue/solid organ transplant
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Toll Free Number
Phone
1-888-577-8839
Email
Trialsites@merck.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
Facility Information:
Facility Name
University of California at San Francisco ( Site 1008)
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
415-514-3878
Facility Name
Yale-New Haven Hospital-Yale Cancer Center ( Site 1011)
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
203-500-0834
Facility Name
University of Chicago ( Site 1013)
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
855-702-8222
Facility Name
University of Iowa ( Site 1012)
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
319-384-8076
Facility Name
Henry Ford Health System ( Site 1014)
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Individual Site Status
Completed
Facility Name
Laura and Isaac Perlmutter Cancer Center ( Site 1016)
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
347-880-5351
Facility Name
Memorial Sloan Kettering Cancer Center ( Site 1002)
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
646-497-9068
Facility Name
Duke Cancer Institute ( Site 1015)
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
919-681-1030
Facility Name
UPMC Cancer Center/Hillman Cancer Center ( Site 1017)
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
412-623-4891
Facility Name
UTSW Medical Center ( Site 1003)
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390-7208
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
214-648-7097
Facility Name
Western Sydney Local Health District ( Site 1601)
City
Blacktown
State/Province
New South Wales
ZIP/Postal Code
2148
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+61286708421
Facility Name
St George Hospital ( Site 1602)
City
Kogarah
State/Province
New South Wales
ZIP/Postal Code
2217
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+61291132977
Facility Name
Royal Brisbane and Women s Hospital ( Site 1603)
City
Herston
State/Province
Queensland
ZIP/Postal Code
4029
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
61736467983
Facility Name
Austin Health ( Site 1600)
City
Heidelberg
State/Province
Victoria
ZIP/Postal Code
3084
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+61394963577
Facility Name
Princess Margaret Cancer Centre ( Site 1101)
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1Z5
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
4169464501x5606
Facility Name
Jewish General Hospital ( Site 1100)
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1E2
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
5143408222x24572
Facility Name
James Lind Centro de Investigación del Cáncer ( Site 2108)
City
Temuco
State/Province
Araucania
ZIP/Postal Code
4800827
Country
Chile
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+56994443272
Facility Name
CIDO SpA-Oncology ( Site 2106)
City
Temuco
State/Province
Araucania
ZIP/Postal Code
4810148
Country
Chile
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
569 5 798 31 73
Facility Name
FALP-UIDO ( Site 2100)
City
Santiago
State/Province
Region M. De Santiago
ZIP/Postal Code
7500921
Country
Chile
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
56224457254
Facility Name
Oncovida ( Site 2107)
City
Santiago
State/Province
Region M. De Santiago
ZIP/Postal Code
7510032
Country
Chile
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
5624205100
Facility Name
Bradfordhill-Clinical Area ( Site 2101)
City
Santiago
State/Province
Region M. De Santiago
ZIP/Postal Code
8420383
Country
Chile
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+56998744662
Facility Name
ONCOCENTRO APYS-ACEREY ( Site 2103)
City
Viña del Mar
State/Province
Valparaiso
ZIP/Postal Code
2520598
Country
Chile
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+56992369820
Facility Name
Sociedad De Oncologia Y Hematologia Del Cesar-Oncology ( Site 1905)
City
Valledupar
State/Province
Cesar
ZIP/Postal Code
200001
Country
Colombia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
00573128385292
Facility Name
Oncomédica S.A.S ( Site 1904)
City
Montería
State/Province
Cordoba
ZIP/Postal Code
230002
Country
Colombia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
3105394868
Facility Name
Clinica Colsanitas S.A, Sede Clínica Universitaria Colombia-Center Investigator ( Site 1900)
City
Bogota
State/Province
Distrito Capital De Bogota
ZIP/Postal Code
111321
Country
Colombia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
573103469453
Facility Name
Fundacion Valle del Lili- CIC ( Site 1901)
City
Cali
State/Province
Valle Del Cauca
ZIP/Postal Code
760032
Country
Colombia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
573012895296
Facility Name
Institut De Cancerologie De Lorraine ( Site 1204)
City
Vandoeuvre les Nancy
State/Province
Ain
ZIP/Postal Code
54519
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+33383598574
Facility Name
Institut de cancérologie Strasbourg Europe (ICANS) ( Site 1203)
City
Strasbourg
State/Province
Alsace
ZIP/Postal Code
67033
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+33368767360
Facility Name
Institut Claudius Regaud ( Site 1200)
City
Toulouse Cedex 9
State/Province
Haute-Garonne
ZIP/Postal Code
31059
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
0033531155101
Facility Name
Gustave Roussy ( Site 1202)
City
Villejuif
State/Province
Val-de-Marne
ZIP/Postal Code
94800
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
33142114211
Facility Name
Országos Onkológiai Intézet-Urogenitális Tumorok és Klinikai Farmakológiai Osztály ( Site 2301)
City
Budapest
State/Province
Pest
ZIP/Postal Code
1122
Country
Hungary
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
3612248600
Facility Name
Rambam MC ( Site 1500)
City
Haifa
ZIP/Postal Code
3525408
Country
Israel
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
97247776750
Facility Name
Hadassah Medical Center-Oncology ( Site 1504)
City
Jerusalem
ZIP/Postal Code
9112001
Country
Israel
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
97226777825
Facility Name
Rabin Medical Center ( Site 1502)
City
Petah Tiqwa
ZIP/Postal Code
4941492
Country
Israel
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
97239378003
Facility Name
Sheba Medical Center - Oncology Division ( Site 1501)
City
Ramat Gan
ZIP/Postal Code
52621
Country
Israel
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+97235302191
Facility Name
Sourasky Medical Center ( Site 1503)
City
Tel Aviv
ZIP/Postal Code
6423906
Country
Israel
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
97236947284
Facility Name
Asan Medical Center ( Site 1800)
City
Songpagu
State/Province
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+82230106981
Facility Name
Severance Hospital ( Site 1802)
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+82222281004
Facility Name
Samsung Medical Center ( Site 1801)
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+82234103000
Facility Name
Nederlands Kanker Instituut - Antoni van Leeuwenhoek (NKI-AVL)-medical oncology ( Site 2402)
City
Amsterdam
State/Province
Noord-Holland
ZIP/Postal Code
1066 CX
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+31622899604
Facility Name
Erasmus Medisch Centrum ( Site 2401)
City
Rotterdam
State/Province
Zuid-Holland
ZIP/Postal Code
3015 GD
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+31107041754
Facility Name
Auckland City Hospital ( Site 1700)
City
Auckland
ZIP/Postal Code
1023
Country
New Zealand
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+6493074949
Facility Name
Centrum Onkologii im. Prof. Franciszka Lukaszczyka-Ambulatorium Chemioterapii ( Site 2201)
City
Bydgoszcz
State/Province
Kujawsko-pomorskie
ZIP/Postal Code
85-796
Country
Poland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
48501446778
Facility Name
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Oddzial Badan Wczesnych Faz ( Site 2200
City
Warszawa
State/Province
Mazowieckie
ZIP/Postal Code
02-781
Country
Poland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
48504340022
Facility Name
Uniwersyteckie Centrum Kliniczne-Early Clinical Trials Unit ( Site 2202)
City
Gdańsk
State/Province
Pomorskie
ZIP/Postal Code
80-952
Country
Poland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+48585844466
Facility Name
Hospital Universitari Vall d Hebron ( Site 1300)
City
Barcelona
State/Province
Cataluna
ZIP/Postal Code
08035
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+34934894350
Facility Name
Hospital Universitario Ramon y Cajal ( Site 1301)
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+34913368263
Facility Name
Southampton General Hospital ( Site 1403)
City
Southampton
State/Province
England
ZIP/Postal Code
SO16 6YD
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+44 023 8077 7222
Facility Name
The Beatson West of Scotland Cancer Centre ( Site 1405)
City
Glasgow
State/Province
Glasgow City
ZIP/Postal Code
G12 0YN
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+441413017064
Facility Name
Royal Preston Hospital ( Site 1406)
City
Preston
State/Province
Lancashire
ZIP/Postal Code
PR2 9HT
Country
United Kingdom
Individual Site Status
Active, not recruiting
Facility Name
Leicester Royal Infirmary ( Site 1408)
City
Leicester
State/Province
Leicestershire
ZIP/Postal Code
LE1 5WW
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+44 116 258 5642
Facility Name
Barts Health NHS Trust ( Site 1401)
City
London
State/Province
London, City Of
ZIP/Postal Code
EC1A 7BE
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
02073777000
Facility Name
Western General Hospital ( Site 1402)
City
Edinburgh
State/Province
Midlothian
ZIP/Postal Code
EH42XU
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+441315373607
Facility Name
Velindre Cancer Centre Hospital ( Site 1407)
City
Cardiff
State/Province
Wales
ZIP/Postal Code
CF14 2TL
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
02920615888
Facility Name
The Christie NHS Foundation Trust ( Site 1400)
City
Manchester
ZIP/Postal Code
M20 4BX
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
441614463000

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Links:
URL
http://merckoncologyclinicaltrials.com
Description
Merck Oncology Clinical Trials Information

Learn more about this trial

Substudy 03A: A Study of Immune and Targeted Combination Therapies in Participants With First Line (1L) Renal Cell Carcinoma (MK-3475-03A)

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