Renal Cell CarcinomaPhase 1NCT05030506
A Study of Belzutifan (MK-6482) as Monotherapy and in Combination With Lenvatinib (E7080/MK-7902) With or Without Pembrolizumab (MK-3475) in China Participants With Advanced Renal Cell Carcinoma (MK-6482-010)
A Phase 1 study testing Belzutifan, Pembrolizumab and Lenvatinib in people with Renal Cell Carcinoma, run by Merck Sharp & Dohme LLC at 5 sites in China.
Trial summary
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic profiles, and preliminary efficacy of belzutifan as monotherapy followed by belzutifan+lenvatinib combination therapy, as well as belzutifan combined with lenvatinib and pembrolizumab in China participants with… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Renal Cell Carcinoma
- What is being tested?
- Belzutifan, Pembrolizumab and Lenvatinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 5 sitesChina
- Study dates
- 13 Oct 2021to 30 Jun 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Has a histologically confirmed diagnosis of unresectable, locally advanced or metastatic clear cell renal cell carcinoma (RCC).
- Has measurable disease per RECIST 1.1.
- Has adequate organ function.
- Has adequately controlled blood pressure (BP).
- If participants received major surgery or radiation therapy of >30 Gy, they must have recovered from the toxicity and/or complications from the intervention.
- Has resolution of the toxic effect(s) of the most recent prior therapy.
Show all 17Show fewer
- Participants receiving bone resorptive therapy must have therapy initiated at least 2 weeks prior to allocation.
- Is Chinese descent, defined as both biological parents and all biological grandparents are of Chinese descent.
- Male Participants:
- Must be willing to use an adequate method of contraception.
- Female Participants:
- Must be a woman of non-childbearing potential (WONCBP) or have a negative urine or serum pregnancy test and must be willing to use an adequate method of contraception.
- For Belzutifan + Lenvatinib treatment:
- Has progressed on or after having received systemic treatment for locally advanced or metastatic RCC.
- Has no more than 3 prior systemic regimens for locally advanced or metastatic RCC.
- For Belzutifan + Lenvatinib + Pembrolizumab treatment:
- Has received no prior systemic therapy for advanced RCC.
Who cannot join
- Is a woman of childbearing potential (WOCBP) who has a positive urine pregnancy test within 24 hours prior to first dose of study intervention.
- Has any of the following: A pulse oximeter reading <92%, or requires intermittent supplemental oxygen, or requires chronic supplemental oxygen.
- Has a 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 clinically significant cardiac disease.
- Has symptomatic pleural effusion.
Show all 33Show fewer
- Has a history of inflammatory bowel disease.
- Has preexisting ≥Grade 3 gastrointestinal or non-gastrointestinal fistula.
- Has clinically significant hematuria, hematemesis or hemoptysis of red blood, or other history of significant bleeding within 3 months before administration of the first dose of study intervention.
- Has other clinically significant disorders such as: A serious active non-healing wound/ulcer/bone fracture, requirement for hemodialysis or peritoneal dialysis or a history of allogenic tissue/solid organ transplantation.
- Received colony-stimulating factors, granulocyte macrophage colony-stimulating factor (GMCSF) or recombinant EPO within 28 days prior to the first dose of study intervention.
- Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study.
- Is unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption.
- Has received prior treatment with belzutifan.
- Has received prior treatment with lenvatinib.
- Has received any type of systemic anticancer antibody (including investigational antibody) ≤28 days prior to allocation.
- Has received / will be receiving any traditional Chinese medicines.
- Has received prior radiotherapy within 2 weeks prior to first dose of study intervention. Participants must have recovered from all radiation-related toxicities and not require corticosteroids.
- Is receiving concomitant treatment, in therapeutic doses, with anticoagulants.
- Is receiving chronic systemic steroids therapy (at doses >10 mg daily of prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention.
- Is currently participating in a study of an investigational agent or is currently using an investigational device.
- Has an active infection requiring systemic therapy.
- Has a known history of Human Immunodeficiency Virus (HIV) infection.
- Has a known history of Hepatitis B or known active Hepatitis C virus infection.
- Has a known history of active tuberculosis.
- Has radiographic evidence of intratumoral cavitation, encasement or invasion of a major blood vessel.
- Has known hypersensitivity or allergy to the active pharmaceutical ingredient or any component of the study intervention (belzutifan or lenvatinib) formulations.
- Has had major surgery within 4 weeks prior to first dose of study intervention.
- For Belzutifan + Lenvatinib + Pembrolizumab treatment:
- Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
- Has a history of hypersensitivity reaction to the active pharmaceutical ingredient or any component of pembrolizumab or monoclonal antibody (mAb).
- Has an active autoimmune disease that has required systemic treatment in the past 2 years.
- Has received a live vaccine within 30 days prior to the first dose of study intervention.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
China5 sites
Beijing Cancer hospital-Digestive Oncology ( Site 0001)
Beijing, Beijing Municipality, 100142
SUN YAT-SEN UNIVERSITY CANCER CENTRE-Urology Surgery Department ( Site 0005)
Guangzhou, Guangdong, 510060
The Second Affiliated hospital of Zhejiang University school of medicine-Urology ( Site 0007)
Hangzhou, Zhejiang, 310052
Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School-Urology ( S
Nanjing, Jiangsu, 210000
Tianjin Medical University Cancer Institute and Hospital ( Site 0003)
Tianjin, Tianjin Municipality, 300060
About this study
Official title: An Open-Label, Phase 1 Study of MK-6482 as Monotherapy and in Combination With Lenvatinib (MK-7902) With or Without Pembrolizumab (MK-3475) in China Participants With Advanced Renal Cell Carcinoma
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic profiles, and preliminary efficacy of belzutifan as monotherapy followed by belzutifan+lenvatinib combination therapy, as well as belzutifan combined with lenvatinib and pembrolizumab in China participants with advanced renal cell carcinoma.
- Conditions
- Renal Cell Carcinoma
- Being tested
- Belzutifan, Pembrolizumab, Lenvatinib
- Keywords
- Belzutifan, Pembrolizumab, Programmed Cell Death-1 (PD1), Hypoxia inducible factor 2 alpha (HIF-2 alpha), Hypoxia inducible factor 2α (HIF-2α), Renal Cell Carcinoma (RCC), Kidney Cancer, MK-6482, MK6482, PT-2977, PT2977, MK-3475 KEYTRUDA®, MK-7902, E7080, LENVIMA®
- Medical subject headings
- Carcinoma, Renal Cell, Kidney Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BelzutifanDrug
Also called MK-6482, PT2977
40 mg tablet administered orally at a dose of 120 mg
PembrolizumabBiological
Also called MK-3475 KEYTRUDA®
25 mg/mL solution for Infusion in a single-dose vial administered intravenously at a dose of 400 mg
LenvatinibDrug
Also called MK-7902, E7080, LENVIMA®
10 mg capsule administered orally at a dose of 20 mg
| Study group | Role | What they receive |
|---|---|---|
| Belzutifan + Lenvatinib | Experimental | Participants will receive a daily oral dose of 120 mg of belzutifan monotherapy for 3 weeks, followed by a combination of a daily oral dose of 120 mg of belzutifan with a daily oral dose of 20 mg of lenvatinib until progressive disease or discontinuation. Receives: Drug: Belzutifan; Drug: Lenvatinib |
| Belzutifan + Lenvatinib + Pembrolizumab | Experimental | Participants will receive an intravenous dose of 400 mg of pembrolizumab once every six weeks for up to 18 infusions (up to 2 years) in combination with a daily oral dose of 120 mg of belzutifan and a daily oral dose of 20 mg of lenvatinib until progressive disease or discontinuation. Receives: Drug: Belzutifan; Biological: Pembrolizumab; Drug: Lenvatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants who experienced dose-limiting toxicities (DLTs)
A DLT is defined as an event with toxicity including the type, severity, time of onset, time of resolution, and the probable association with study treatment that are not due to pre-existing conditions as defined by the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE 5.0). Number of participants who experience a DLT per CTCAE 5.0 will be reported.
Measured: Up to approximately 21 days
Number of participants who experienced an adverse event (AE)
An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The number of participants who experience an AE in the study will be reported.
Measured: Up to approximately 68 months
Number of participants who discontinued study treatment due to an AE
An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The number of participants who discontinued from the study treatment due to an AE will be reported.
Measured: Up to approximately 68 months
Area under the concentration-time curve from 0-24 hours (AUC0-24) of belzutifan after single dose (Cohort 1)
AUC is a measure of plasma drug concentration and time and is estimated as the area under the plot of plasma concentration against time after drug administration. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine AUC0-24 of belzutifan.
Measured: Pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose
Maximum concentration (Cmax) of belzutifan after single dose (Cohort 1)
Cmax is the maximum concentration of the drug observed in plasma. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine Cmax of belzutifan.
Measured: Pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose
Time at maximum concentration (Tmax) of belzutifan after single dose (Cohort 1)
Tmax is the amount of time that a drug is present at the maximum concentration is observed in plasma. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine the Tmax of belzutifan.
Measured: Pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose
Steady state area under the concentration-time curve from 0-24 hours (AUC0-24,ss) of belzutifan after multiple doses (Cohort 1)
AUC0-24,ss is a measure of plasma drug concentration and time and is estimated as the area under the plot of plasma concentration against time after drug administration. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine AUC0-24,ss of belzutifan.
Measured: Pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose
Steady state maximum concentration (Cmax,ss) of belzutifan after multiple doses (Cohort 1)
Cmax,ss is the maximum concentration of the drug observed in plasma. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine Cmax,ss of belzutifan.
Measured: Pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose
Time at maximum concentration (Tmax) of belzutifan after multiple doses (Cohort 1)
Tmax is the amount of time that a drug is present at the maximum concentration is observed in plasma. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine the Tmax of belzutifan.
Measured: Pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose
Apparent t½ of belzutifan after multiple doses (Cohort 1)
T1/2 is a measure of how long it takes to clear 50% of the drug after reaching Cmax. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine t1/2 of belzutifan.
Measured: Pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose.
Steady state trough concentration (Ctrough,ss) of belzutifan after multiple doses (Cohort 1)
Ctrough,ss is the lowest concentration reached by a drug before the next dose is administered. Blood samples taken at predose and at specified times post dose will be used to determine Ctrough,ss of belzutifan.
Measured: Pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose
Accumulation ratio (RAC) of belzutifan after multiple doses (Cohort 1)
RAC is the ratio of accumulation of a drug under steady state conditions after repeated administration as compared to a single dose. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine RAC of belzutifan.
Measured: Pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose
Apparent oral clearance (CL/F) of belzutifan after multiple doses (Cohort 1)
CL/F is the apparent total clearance of the drug from plasma after oral administration. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine CL/F of belzutifan.
Measured: Pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose
Apparent oral volume (Vz/F) of belzutifan after multiple doses (Cohort 1)
Vz/F is the apparent volume of distribution of the drug during terminal phase after non-intravenous administration. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine Vz/F of belzutifan.
Measured: Pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose
Secondary outcomes (9)
Objective response rate (ORR)
ORR is defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors 1.1 (RECIST 1.1.) The percentage of participants who experience a CR or PR as assessed by blinded independent central review based on RECIST 1.1 will be presented.
Measured: Up to approximately 68 months
Duration of response (DOR)
For participants who demonstrate a confirmed Complete Response (CR: Disappearance of all target lesions) or confirmed Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD was 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 have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD. The DOR as assessed by blinded independent central review will be presented.
Measured: Up to approximately 68 months
Progression-free survival (PFS)
PFS is defined as the time from first dose of study treatment to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥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 ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by blinded independent central review will be presented.
Measured: Up to approximately 68 months
Overall survival (OS)
OS, defined as the time from first dose of study treatment to death due to any cause, will be presented.
Measured: Up to approximately 68 months
Steady state trough concentration (Ctrough,ss) of belzutifan (Cohort 2)
Cmin,ss is the minimum plasma drug concentration. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine Cmin,ss of belzutifan.
Measured: Pre-dose, and 1, 2 and 4 hours postdose
Percent change from baseline in erythropoietin (EPO) level
Percent change from baseline in EPO level will be measured and presented.
Measured: Baseline, up to approximately 6 weeks
Cmax,ss of belzutifan for UGT2B17 and CYP2C19 phenotypes
Cmax,ss is the maximum concentration of the drug observed in plasma. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine Cmax,ss of belzutifan for participants with UGT2B17 and CYP2C19 phenotypes.
Measured: Week 3 Day 7: pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose
AUCss of belzutifan for UGT2B17 and CYP2C19 phenotypes
AUC0-24,ss is a measure of plasma drug concentration vs time and is estimated as the area under the plot of plasma concentration against time after drug administration. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine AUC0-24,ss of belzutifan for participants with UGT2B17 and CYP2C19 phenotypes.
Measured: Week 3 Day 7: pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose
Ctrough,ss of belzutifan for UGT2B17 and CYP2C19 phenotypes
Ctrough,ss is the lowest concentration reached by a drug before the next dose is administered. Blood samples taken at predose and at specified times post dose will be used to determine Ctrough,ss of belzutifan for participants with UGT2B17 and CYP2C19 phenotypes.
Measured: Week 3 Day 7: pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Sep 2021
- Study start13 Oct 2021
- Primary completion30 Jun 2027 (estimated)
- Study completion30 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Renal Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05030506
- Sponsor's protocol ID
- 6482-010
- Other IDs
- MK-6482-010
- Status last verified
- Dec 2025
- First submitted
- 30 Aug 2021
- Last updated
- 18 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Phase 1 Study of MK-6482 as Monotherapy and in Combination With Lenvatinib (MK-7902) With or Without Pembrolizumab (MK-3475) in China Participants With Advanced Renal Cell Carcinoma
- ClinicalTrials.gov ID
- NCT05030506
- Acronym / sponsor ID
- 6482-010
- Conditions
- Renal Cell Carcinoma
- Keywords
- Belzutifan, Pembrolizumab, Programmed Cell Death-1 (PD1), Hypoxia inducible factor 2 alpha (HIF-2 alpha), Hypoxia inducible factor 2α (HIF-2α), Renal Cell Carcinoma (RCC), Kidney Cancer, MK-6482
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 13 Oct 2021 (actual)
- Primary completion
- 30 Jun 2027 (estimated)
- Study completion
- 30 Jun 2027 (estimated)
- First posted
- 1 Sep 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic profiles, and preliminary efficacy of belzutifan as monotherapy followed by belzutifan+lenvatinib combination therapy, as well as belzutifan combined with lenvatinib and pembrolizumab in China participants with advanced renal cell carcinoma.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Belzutifan + Lenvatinib | Experimental | Drug: Belzutifan, Drug: LenvatinibParticipants will receive a daily oral dose of 120 mg of belzutifan monotherapy for 3 weeks, followed by a combination of a daily oral dose of 120 mg of belzutifan with a daily oral dose of 20 mg of lenvatinib until progressive disease or discontinuation. |
| Belzutifan + Lenvatinib + Pembrolizumab | Experimental | Drug: Belzutifan, Biological: Pembrolizumab, Drug: LenvatinibParticipants will receive an intravenous dose of 400 mg of pembrolizumab once every six weeks for up to 18 infusions (up to 2 years) in combination with a daily oral dose of 120 mg of belzutifan and a daily oral dose of 20 mg of lenvatinib until progressive disease or discontinuation. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Has a histologically confirmed diagnosis of unresectable, locally advanced or metastatic clear cell renal cell carcinoma (RCC).
- Has measurable disease per RECIST 1.1.
- Has adequate organ function.
- Has adequately controlled blood pressure (BP).
- If participants received major surgery or radiation therapy of >30 Gy, they must have recovered from the toxicity and/or complications from the intervention.
Key exclusion criteria (33 listed)
- Is a woman of childbearing potential (WOCBP) who has a positive urine pregnancy test within 24 hours prior to first dose of study intervention.
- Has any of the following: A pulse oximeter reading <92%, or requires intermittent supplemental oxygen, or requires chronic supplemental oxygen.
- Has a 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 clinically significant cardiac disease.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BelzutifanAlso: MK-6482, PT297740 mg tablet administered orally at a dose of 120 mg | Drug | Belzutifan + Lenvatinib, Belzutifan + Lenvatinib + Pembrolizumab |
| PembrolizumabAlso: MK-3475 KEYTRUDA®25 mg/mL solution for Infusion in a single-dose vial administered intravenously at a dose of 400 mg | Biological | Belzutifan + Lenvatinib + Pembrolizumab |
| LenvatinibAlso: MK-7902, E7080, LENVIMA®10 mg capsule administered orally at a dose of 20 mg | Drug | Belzutifan + Lenvatinib, Belzutifan + Lenvatinib + Pembrolizumab |
Primary outcome
Number of participants who experienced dose-limiting toxicities (DLTs)
Time frame: Up to approximately 21 days
A DLT is defined as an event with toxicity including the type, severity, time of onset, time of resolution, and the probable association with study treatment that are not due to pre-existing conditions as defined by the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE 5.0). Number of participants who experience a DLT per CTCAE 5.0 will be reported.
Number of participants who experienced an adverse event (AE)
Time frame: Up to approximately 68 months
An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The number of participants who experience an AE in the study will be reported.
Number of participants who discontinued study treatment due to an AE
Time frame: Up to approximately 68 months
An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The number of participants who discontinued from the study treatment due to an AE will be reported.
Area under the concentration-time curve from 0-24 hours (AUC0-24) of belzutifan after single dose (Cohort 1)
Time frame: Pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose
AUC is a measure of plasma drug concentration and time and is estimated as the area under the plot of plasma concentration against time after drug administration. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine AUC0-24 of belzutifan.
Maximum concentration (Cmax) of belzutifan after single dose (Cohort 1)
Time frame: Pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose
Cmax is the maximum concentration of the drug observed in plasma. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine Cmax of belzutifan.
Time at maximum concentration (Tmax) of belzutifan after single dose (Cohort 1)
Time frame: Pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose
Tmax is the amount of time that a drug is present at the maximum concentration is observed in plasma. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine the Tmax of belzutifan.
Steady state area under the concentration-time curve from 0-24 hours (AUC0-24,ss) of belzutifan after multiple doses (Cohort 1)
Time frame: Pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose
AUC0-24,ss is a measure of plasma drug concentration and time and is estimated as the area under the plot of plasma concentration against time after drug administration. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine AUC0-24,ss of belzutifan.
Steady state maximum concentration (Cmax,ss) of belzutifan after multiple doses (Cohort 1)
Time frame: Pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose
Cmax,ss is the maximum concentration of the drug observed in plasma. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine Cmax,ss of belzutifan.
Time at maximum concentration (Tmax) of belzutifan after multiple doses (Cohort 1)
Time frame: Pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose
Tmax is the amount of time that a drug is present at the maximum concentration is observed in plasma. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine the Tmax of belzutifan.
Apparent t½ of belzutifan after multiple doses (Cohort 1)
Time frame: Pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose.
T1/2 is a measure of how long it takes to clear 50% of the drug after reaching Cmax. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine t1/2 of belzutifan.
Steady state trough concentration (Ctrough,ss) of belzutifan after multiple doses (Cohort 1)
Time frame: Pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose
Ctrough,ss is the lowest concentration reached by a drug before the next dose is administered. Blood samples taken at predose and at specified times post dose will be used to determine Ctrough,ss of belzutifan.
Accumulation ratio (RAC) of belzutifan after multiple doses (Cohort 1)
Time frame: Pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose
RAC is the ratio of accumulation of a drug under steady state conditions after repeated administration as compared to a single dose. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine RAC of belzutifan.
Apparent oral clearance (CL/F) of belzutifan after multiple doses (Cohort 1)
Time frame: Pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose
CL/F is the apparent total clearance of the drug from plasma after oral administration. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine CL/F of belzutifan.
Apparent oral volume (Vz/F) of belzutifan after multiple doses (Cohort 1)
Time frame: Pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose
Vz/F is the apparent volume of distribution of the drug during terminal phase after non-intravenous administration. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine Vz/F of belzutifan.
9 secondary outcomes
Objective response rate (ORR)
Time frame: Up to approximately 68 months
Duration of response (DOR)
Time frame: Up to approximately 68 months
Progression-free survival (PFS)
Time frame: Up to approximately 68 months
Overall survival (OS)
Time frame: Up to approximately 68 months
Steady state trough concentration (Ctrough,ss) of belzutifan (Cohort 2)
Time frame: Pre-dose, and 1, 2 and 4 hours postdose
Percent change from baseline in erythropoietin (EPO) level
Time frame: Baseline, up to approximately 6 weeks
Cmax,ss of belzutifan for UGT2B17 and CYP2C19 phenotypes
Time frame: Week 3 Day 7: pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose
AUCss of belzutifan for UGT2B17 and CYP2C19 phenotypes
Time frame: Week 3 Day 7: pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose
Ctrough,ss of belzutifan for UGT2B17 and CYP2C19 phenotypes
Time frame: Week 3 Day 7: pre-dose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2025.
- Merck Clinical Trials InformationLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
Related trials for Renal Cell Carcinoma
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 3
A Study of Belzutifan (MK-6482) in Combination With Lenvatinib Versus Cabozantinib for Treatment of Renal Cell Carcinoma (MK-6482-011)
Carcinoma, Renal Cell
RecruitingPhase 2/3
Testing the Role of DNA Released From Tumor Cells Into the Blood in Guiding the Use of Immunotherapy After Surgical Removal of the Bladder, Kidney, Ureter, and Urethra for Urothelial Cancer Treatment, MODERN Study
Muscle Invasive Bladder Urothelial Carcinoma, Muscle Invasive Renal Pelvis Urothelial Carcinoma
Not yet recruitingPhase 2
Toripalimab and Lenvatinib With or Without SBRT Before Surgery for Non-Clear Cell Kidney Cancer
Nonmetastatic Locally Advanced Non-Clear Cell Renal Cell Carcinoma
Not yet recruitingPhase 2
Pucotenlimab, Lenvatinib, and SBRT Before Surgery for Localized Clear Cell Renal Cell Carcinoma
Localized Clear Cell Renal Cell Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Belzutifan, Pembrolizumab and Lenvatinib in people with Renal Cell Carcinoma, run by Merck Sharp & Dohme LLC at 5 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 18 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants who experienced dose-limiting toxicities (DLTs) (time frame: Up to approximately 21 days). The study lists 14 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2025.