Neoplasms

All Conditions

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Hypoxia

Carcinoma, Renal Cell

Kidney Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Everolimus

Belzutifan

Sirolimus

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immunosuppressive Agents

Immunologic Factors

Participants receive 120 mg of belzutifan orally once daily (QD)

Participants receive 10 mg of Everolimus orally once daily (QD)

Medical Director

The primary objective of this study is to compare belzutifan to everolimus with respect to progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR) and to compare everolimus with respect to overall survival (OS). The hypothesis is that belzutifan is superior to everolimus with respect to PFS and OS.

A Study of Belzutifan (MK-6482) Versus Everolimus in Participants With Advanced Renal Cell Carcinoma (MK-6482-005)

An Open-label, Randomized Phase 3 Study of MK-6482 Versus Everolimus in Participants With Advanced Renal Cell Carcinoma That Has Progressed After Prior PD-1/L1 and VEGF-Targeted Therapies

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

PFS is defined as the time from randomization 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

Time from randomization to death due to any cause

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 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.

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 disease progression or death. The DOR as assessed by blinded independent central review will be presented.

An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. The number of participants who discontinue study treatment due to an AE will be presented.

TTD is defined as the time from baseline to the first onset of a ≥10-point negative change (decrease) from baseline in global health status (Item 29) \& quality of life (Item 30) combined score. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point negative change (decrease) from baseline in global health status and quality of life combined score, will be presented. A longer TTD indicates a better outcome.

TTD is defined as the time from Baseline to the first onset of a ≥10-point negative change (decrease) from Baseline in physical functioning (EORTC QLQ-C30 Items 1-5) score. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point negative change (decrease) from Baseline in physical functioning score, will be presented.

The FKSI-DRS index consists of a 9-item questionnaire that assesses the extent of participant symptoms from kidney cancer over the previous 7 days. Responses are scored on a 5-point scale (0=Not at all to 4=Very much) and summed to generate an index symptom score. These scores can range from 0 to 36, with a higher score indicating more favorable kidney cancer symptom status.

The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses for global health status (Item 29) \& quality of life (Item 30) are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. The change from baseline in EORTC QLQ-C30 Items 29 and 30 scores will be presented.

The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better quality of life. The change from baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) score will be presented.

The EQ-5D-5L questionnaire assesses 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/ depression. Each dimension has 5 response options (no problems, slight problems, moderate problems, severe problems and extreme problems) that reflect increasing levels of difficulty, which are coded on a scale from 1 (no problems) to 5 (extreme problems). The participant is also asked to indicate his/her current health state by selecting the most appropriate level on a visual analog scale from 0 to 100, with 0 being the worst imaginable health state.

Merck Sharp & Dohme LLC

Participants will receive belzutifan 160 mg orally twice daily (BID). Treatment will continue until progressive disease or discontinuation.

Participants will receive belzutifan 160 mg orally three times daily (TID). Treatment will continue until progressive disease or discontinuation.

Participants will receive belzutifan 200 mg orally TID. Treatment will continue until progressive disease or discontinuation.

Participants will receive belzutifan 120 mg orally once daily (QD). Treatment will continue until progressive disease or discontinuation.

40 mg tablet administered orally at a dose of 160 mg, 200 mg, or 120 mg.

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).

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.

A Study of Belzutifan (MK-6482) in Participants With Advanced Clear Cell Renal Cell Carcinoma (MK-6482-018)

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)

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.

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.

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.

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.

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.

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.

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.

Participants receive 200 mg of belzutifan by oral administration, once a day (QD), until disease progression or discontinuation.

Participants receive 120 mg of belzutifan by oral administration, QD, until disease progression or discontinuation.

This study will compare the efficacy and safety of two doses of belzutifan in participants with advanced renal cell carcinoma (RCC) with clear cell component after prior therapy.

The primary hypothesis is that the higher dose of belzutifan is superior to the standard dose in terms of objective response rate (ORR).

A Study of Belzutifan (MK-6482) in Participants With Advanced Renal Cell Carcinoma (MK-6482-013)

Phase 2 Study of MK-6482 in Participants With Advanced Renal Cell Carcinoma

ORR was defined as the percentage of participants who had 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 RECIST 1.1. The percentage of participants who experienced a CR or PR as assessed by blinded independent central review based on RECIST 1.1 was presented.

PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was 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 was also considered PD. PFS as assessed by blinded independent central review was presented.

For participants who demonstrated 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 was defined as the time from first documented evidence of CR or PR until disease progression or death. The DOR as assessed by blinded independent central review was presented.

CBR 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) or stable disease (SD: Neither sufficient decrease to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.) ≥6 months per RECIST 1.1. The percentage of participants with CBR will be presented.

OS was defined as the time from randomization to death due to any cause.

An AE was defined as 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 experienced one or more AEs was presented.

An AE was defined as 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 discontinued study treatment due to an AE was presented.

Blood samples were obtained at designated time points for the determination of the Cmax of belzutifan.

Blood samples were obtained at designated time points for the determination of the Ctrough of belzutifan.

Serious and Other adverse events (AEs) includes all participants who received ≥1 dose of study drug. All-Cause Mortality includes all randomized participants. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study treatment. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" \& "Disease progression" not related to study treatment are excluded as AEs. Data are reported by treatment received.

Participants received 200 mg of belzutifan by oral administration, QD, until disease progression or discontinuation.

Belzutifan 200 mg

Participants received 120 mg of belzutifan by oral administration, QD, until disease progression or discontinuation.

Belzutifan 120 mg

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Participants were stratified by their IMDC Risk Factor (favorable vs. intermediate or poor).

International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) Risk Factor

Senior Vice President, Global Clinical Development

The analysis population consisted of all randomized participants based on the treatment group to which they were randomized.

Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)

Progression-Free Survival (PFS) According to RECIST 1.1 as Assessed by BICR

The analysis population consisted of all randomized participants based on the treatment group to which they were randomized who experienced a confirmed CR or PR.

Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR

Clinical Benefit Rate (CBR) Per RECIST 1.1 as Assessed by BICR

Overall Survival (OS)

All randomized participants who received at least one dose of study treatment.

Number of Participants Who Experience One or More Adverse Events (AEs)

Number of Participants Who Discontinue Study Treatment Due to an AE

The analysis population consisted of all randomized participants based on the treatment group to which they were randomized who had at least 1 measurable belzutifan concentration observation.

Maximum Plasma Concentration (Cmax) of Belzutifan

Trough Plasma Concentration (Ctrough) of Belzutifan

Participants received 200 mg of belzutifan by oral administration, once a day (QD), until disease progression or discontinuation.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Belzutifan (MK-6482) Versus Everolimus in Participants With Advanced Renal Cell Carcinoma (MK-6482-005)	NCT04195750	Carcinoma, Rena...	Belzutifan Everolimus	18 Years -	Merck Sharp & Dohme LLC
A Study of Belzutifan (MK-6482) Versus Everolimus in Participants With Advanced Renal Cell Carcinoma (MK-6482-005)	NCT04195750	Carcinoma, Rena...	Belzutifan Everolimus	18 Years -	Merck Sharp & Dohme LLC
A Study of Belzutifan (MK-6482) in Participants With Advanced Clear Cell Renal Cell Carcinoma (MK-6482-018)	NCT04846920	Carcinoma, Rena...	Belzutifan	18 Years -	Merck Sharp & Dohme LLC
A Study of Belzutifan (MK-6482) in Participants With Advanced Renal Cell Carcinoma (MK-6482-013)	NCT04489771	Carcinoma, Rena...	Belzutifan	18 Years -	Merck Sharp & Dohme LLC

Spots Global Cancer Trial Database for hypoxia inducible factor (hif)