Carcinoma, Renal CellPhase 1NCT04846920
A Study of Belzutifan (MK-6482) in Participants With Advanced Clear Cell Renal Cell Carcinoma (MK-6482-018)
A Phase 1 study testing Belzutifan in people with Carcinoma, Renal Cell, run by Merck Sharp & Dohme LLC at 4 sites in United States.
Trial summary
The goal of this study is to evaluate the safety, tolerability and pharmacokinetics of escalating doses of belzutifan as second line positive (2L+) treatment in participants with advanced clear cell renal cell carcinoma (ccRCC). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Renal Cell
- What is being tested?
- Belzutifan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 4 sitesUnited States
- Study dates
- 14 Jun 2021to 11 Apr 2026
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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/metastatic RCC with clear cell component (with or without sarcomatoid features) (may include participants with a diagnosis of von Hippel-Lindau [VHL] associated ccRCC).
- Has experienced disease progression on or after having received at least one previous systemic treatment for advanced ccRCC.
- Shows adequate organ function.
- Male participants are eligible to participate if they are abstinent from heterosexual intercourse or agree to use contraception during the intervention period and for at least 7 days after the last dose of study intervention.
- A female participant is eligible to participate if she is not pregnant or breastfeeding, and is not a woman of childbearing potential (WOCBP) or is a WOCBP and using contraception or is abstinent from heterosexual intercourse during the intervention period and for at least 30 days after the last dose of study intervention.
Who cannot join
- Has hypoxia, 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. Note: The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, in situ cervical cancer, or other in situ cancers.
- Has any history of or current brain or meningeal metastasis.
- Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction, percutaneous transluminal coronary angioplasty (PTCA), or coronary artery bypass graft surgery (CABG) ≤6 months from Day 1 of study drug administration, or New York Heart Association Class III or IV congestive heart failure. Medically controlled arrhythmia stable on medication is permitted.
- Has moderate to severe hepatic impairment.
- Has an active infection requiring therapy (includes tuberculosis).
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- Has known human immunodeficiency virus (HIV) and/or hepatitis B or C infections or is known to be positive for hepatitis B surface antigen (HBsAg)/hepatitis B virus (HBV) deoxy ribonucleic acid (DNA) or hepatitis C antibody or ribonucleic acid (RNA).
- Has a history or current evidence of a gastrointestinal (GI) condition (eg, inflammatory bowel disease, Crohn's disease, ulcerative colitis) or impaired liver function.
- Has had major surgery ≤3 weeks prior to first dose of study intervention.
- Has received prior treatment with belzutifan.
- Has received any type of systemic anticancer antibody (including investigational antibody) ≤4 weeks prior to the first dose of study intervention.
- Has recovered from all AEs due to previous therapies to ≤ Grade 1 or baseline. Participants with a ≤ Grade 2 neuropathy may be eligible.
- Has received prior radiotherapy within 2 weeks prior to randomization.
- Has received colony-stimulating factors (CSFs) (e.g., granulocyte-CSF [G-CSF], granulocyte monocyte-CSF [GM-CSF] or recombinant erythropoietin [EPO]) ≤28 days prior to the first dose of study intervention.
- Has participated and received study intervention in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention. Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been at least 4 weeks since the last dose of the previous investigational agent.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
University of Michigan ( Site 1006)
Ann Arbor, Michigan, 48109
Beth Israel Deaconess Medical Center ( Site 1002)
Boston, Massachusetts, 02215
University of Texas MD Anderson Cancer Center-Genitourinary Medical Oncology ( Site 1007)
Houston, Texas, 77030
Vanderbilt University Medical Center-Vanderbilt-Ingram Cancer Center ( Site 1005)
Nashville, Tennessee, 37232
About this study
Official title: A Phase 1, Dose-escalation Study to Evaluate Safety and Tolerability of Belzutifan (MK-6482) in Participants With Advanced Clear Cell Renal Cell Carcinoma (ccRCC)
The goal of this study is to evaluate the safety, tolerability and pharmacokinetics of escalating doses of belzutifan as second line positive (2L+) treatment in participants with advanced clear cell renal cell carcinoma (ccRCC).
- Conditions
- Carcinoma, Renal Cell
- Being tested
- Belzutifan
- Keywords
- Hypoxia inducible factor (HIF), Hypoxia inducible factor 2 alpha (HIF-2α)
- Medical subject headings
- Carcinoma, Renal Cell
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, WELIREG™
40 mg tablet administered orally at a dose of 160 mg, 200 mg, or 120 mg.
| Study group | Role | What they receive |
|---|---|---|
| Belzutifan 160 mg BID | Experimental | Participants will receive belzutifan 160 mg orally twice daily (BID). Treatment will continue until progressive disease or discontinuation. Receives: Drug: Belzutifan |
| Belzutifan 160 mg TID | Experimental | Participants will receive belzutifan 160 mg orally three times daily (TID). Treatment will continue until progressive disease or discontinuation. Receives: Drug: Belzutifan |
| Belzutifan 200 mg TID | Experimental | Participants will receive belzutifan 200 mg orally TID. Treatment will continue until progressive disease or discontinuation. Receives: Drug: Belzutifan |
| Belzutifan 120 mg QD | Experimental | Participants will receive belzutifan 120 mg orally once daily (QD). Treatment will continue until progressive disease or discontinuation. Receives: Drug: Belzutifan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants Who Experience at Least One Adverse Event (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 percentage of participants who experience at least one AE will be reported.
Measured: Up to ~49.5 months
Percentage 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 percentage of participants who discontinue study treatment due to an AE will be reported.
Measured: Up to ~48.5 months
Percentage of Participants Who Modify or Interrupt 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 percentage of participants who modify or interrupt study treatment due to an AE will be reported.
Measured: Up to ~48.5 months
Percentage of Participants Who Experience at Least One Dose-limiting Toxicity (DLT)
A DLT consists of one or more of the following toxicities: (1) Grade 3 or 4 hypoxia or dyspnea (2) Grade 3 or 4 nausea, vomiting, or diarrhea if persistent for >48 hours despite therapy (3) Grade 3 or 4 cardiovascular, vascular, or thrombotic events (4) Nonhematologic AE ≥Grade 3 in severity (5) Grade 4 nonhematologic toxicity (6) Grade 3 or 4 hematologic toxicities (7) Grade 3 or 4 febrile neutropenia (8) Grade 3 or 4 nonhematologic laboratory value (9) >2 weeks delay in dosing due to intervention-related toxicity (10) Intervention-related toxicity causing intervention discontinuation in the first 21 days of dosing (11) Missing >20% of belzutifan doses due to drug-related AEs in the first 21 days. (12) Grade 5 toxicity. The percentage of participants who experience at least one DLT will be reported.
Measured: Up to ~21 days
Secondary outcomes (3)
Area Under the Plasma Concentration Time Curve (AUC) of Belzutifan
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 belzutifan administration. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine AUC.
Measured: Day 1, Day 21: pre-dose, 0.5, 1, 1.5, 2, 4, and 6 hours post-dose; Day 2: pre-dose and 2 hours post-dose
Maximum Observed Plasma Concentration (Cmax) of Belzutifan
Cmax is the maximum concentration of belzutifan observed in plasma. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine Cmax.
Measured: Day 1, Day 21: pre-dose, 0.5, 1, 1.5, 2, 4, and 6 hours post-dose; Day 2: pre-dose and 2 hours post-dose
Minimum Observed Plasma Concentration (Cmin) of Belzutifan
Cmin is the minimum concentration of belzutifan observed in plasma after its administration and just prior to administration of a subsequent dose. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine Cmin.
Measured: Day 1, Day 21: pre-dose, 0.5, 1, 1.5, 2, 4, and 6 hours post-dose; Day 2: pre-dose and 2 hours post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2021
- Study start14 Jun 2021
- Primary completion11 Apr 2026
- Study completion11 Apr 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carcinoma, Renal CellStudies 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
- Sequential
- Model description
- The "Belzutifan 160 mg BID", "Belzutifan 160 mg TID" and "Belzutifan 200 mg TID" study arms will be enrolled sequentially; the "Belzutifan 120 mg QD" study arm will be enrolled in parallel to the "Belzutifan 160 mg BID", "Belzutifan 160 mg TID" and "Belzutifan 200 mg TID" arms.
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
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
- NCT04846920
- Sponsor's protocol ID
- 6482-018
- Other IDs
- MK-6482-018
- Status last verified
- May 2026
- First submitted
- 7 Apr 2021
- Last updated
- 22 May 2026
- 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 22 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Dose-escalation Study to Evaluate Safety and Tolerability of Belzutifan (MK-6482) in Participants With Advanced Clear Cell Renal Cell Carcinoma (ccRCC)
- ClinicalTrials.gov ID
- NCT04846920
- Acronym / sponsor ID
- 6482-018
- Conditions
- Carcinoma, Renal Cell
- Keywords
- Hypoxia inducible factor (HIF), Hypoxia inducible factor 2 alpha (HIF-2α)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 14 Jun 2021 (actual)
- Primary completion
- 11 Apr 2026 (actual)
- Study completion
- 11 Apr 2026 (actual)
- First posted
- 15 Apr 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 goal of this study is to evaluate the safety, tolerability and pharmacokinetics of escalating doses of belzutifan as second line positive (2L+) treatment in participants with advanced clear cell renal cell carcinoma (ccRCC).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- The "Belzutifan 160 mg BID", "Belzutifan 160 mg TID" and "Belzutifan 200 mg TID" study arms will be enrolled sequentially; the "Belzutifan 120 mg QD" study arm will be enrolled in parallel to the "Belzutifan 160 mg BID", "Belzutifan 160 mg TID" and "Belzutifan 200 mg TID" arms.
| Arm | Type | Receives |
|---|---|---|
| Belzutifan 160 mg BID | Experimental | Drug: BelzutifanParticipants will receive belzutifan 160 mg orally twice daily (BID). Treatment will continue until progressive disease or discontinuation. |
| Belzutifan 160 mg TID | Experimental | Drug: BelzutifanParticipants will receive belzutifan 160 mg orally three times daily (TID). Treatment will continue until progressive disease or discontinuation. |
| Belzutifan 200 mg TID | Experimental | Drug: BelzutifanParticipants will receive belzutifan 200 mg orally TID. Treatment will continue until progressive disease or discontinuation. |
| Belzutifan 120 mg QD | Experimental | Drug: BelzutifanParticipants will receive belzutifan 120 mg orally once daily (QD). Treatment will continue 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 (5 listed)
- Has a histologically-confirmed diagnosis of unresectable, locally advanced/metastatic RCC with clear cell component (with or without sarcomatoid features) (may include participants with a diagnosis of von Hippel-Lindau [VHL] associated ccRCC).
- Has experienced disease progression on or after having received at least one previous systemic treatment for advanced ccRCC.
- Shows adequate organ function.
- Male participants are eligible to participate if they are abstinent from heterosexual intercourse or agree to use contraception during the intervention period and for at least 7 days after the last dose of study intervention.
- A female participant is eligible to participate if she is not pregnant or breastfeeding, and is not a woman of childbearing potential (WOCBP) or is a WOCBP and using contraception or is abstinent from heterosexual intercourse during the intervention period and for at least 30 days after the last dose of study intervention.
Key exclusion criteria (15 listed)
- Has hypoxia, 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. Note: The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, in situ cervical cancer, or other in situ cancers.
- Has any history of or current brain or meningeal metastasis.
- Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction, percutaneous transluminal coronary angioplasty (PTCA), or coronary artery bypass graft surgery (CABG) ≤6 months from Day 1 of study drug administration, or New York Heart Association Class III or IV congestive heart failure. Medically controlled arrhythmia stable on medication is permitted.
- Has moderate to severe hepatic impairment.
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, PT2977, WELIREG™40 mg tablet administered orally at a dose of 160 mg, 200 mg, or 120 mg. | Drug | Belzutifan 120 mg QD, Belzutifan 160 mg BID, Belzutifan 160 mg TID, Belzutifan 200 mg TID |
Primary outcome
Percentage of Participants Who Experience at Least One Adverse Event (AE)
Time frame: Up to ~49.5 months
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 percentage of participants who experience at least one AE will be reported.
Percentage of Participants Who Discontinue Study Treatment Due to an AE
Time frame: Up to ~48.5 months
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 percentage of participants who discontinue study treatment due to an AE will be reported.
Percentage of Participants Who Modify or Interrupt Study Treatment Due to an AE
Time frame: Up to ~48.5 months
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 percentage of participants who modify or interrupt study treatment due to an AE will be reported.
Percentage of Participants Who Experience at Least One Dose-limiting Toxicity (DLT)
Time frame: Up to ~21 days
A DLT consists of one or more of the following toxicities: (1) Grade 3 or 4 hypoxia or dyspnea (2) Grade 3 or 4 nausea, vomiting, or diarrhea if persistent for >48 hours despite therapy (3) Grade 3 or 4 cardiovascular, vascular, or thrombotic events (4) Nonhematologic AE ≥Grade 3 in severity (5) Grade 4 nonhematologic toxicity (6) Grade 3 or 4 hematologic toxicities (7) Grade 3 or 4 febrile neutropenia (8) Grade 3 or 4 nonhematologic laboratory value (9) >2 weeks delay in dosing due to intervention-related toxicity (10) Intervention-related toxicity causing intervention discontinuation in the first 21 days of dosing (11) Missing >20% of belzutifan doses due to drug-related AEs in the first 21 days. (12) Grade 5 toxicity. The percentage of participants who experience at least one DLT will be reported.
3 secondary outcomes
Area Under the Plasma Concentration Time Curve (AUC) of Belzutifan
Time frame: Day 1, Day 21: pre-dose, 0.5, 1, 1.5, 2, 4, and 6 hours post-dose; Day 2: pre-dose and 2 hours post-dose
Maximum Observed Plasma Concentration (Cmax) of Belzutifan
Time frame: Day 1, Day 21: pre-dose, 0.5, 1, 1.5, 2, 4, and 6 hours post-dose; Day 2: pre-dose and 2 hours post-dose
Minimum Observed Plasma Concentration (Cmin) of Belzutifan
Time frame: Day 1, Day 21: pre-dose, 0.5, 1, 1.5, 2, 4, and 6 hours post-dose; Day 2: pre-dose and 2 hours post-dose
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2026.
- Merck Clinical Trials InformationLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
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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
4 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 in people with Carcinoma, Renal Cell, run by Merck Sharp & Dohme LLC at 4 sites in United States.
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 5 inclusion and 15 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: finished, as of the sponsor's last update on 22 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Percentage of Participants Who Experience at Least One Adverse Event (AE) (time frame: Up to ~49.5 months). The study lists 4 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 22 May 2026.