A Study of Belzutifan (MK-6482) in Combination With Lenvatinib Versus Cabozantinib for Treatment of Renal Cell Carcinoma (MK-6482-011)

• ClinicalTrials.gov Identifier: NCT04586231
• Recruitment Status: Recruiting
• First Posted: October 14, 2020
• Last Update Posted: August 12, 2022
• Sponsor: Merck Sharp & Dohme LLC
• Collaborator: Eisai Inc.
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

Tracking Information

• First Submitted Date: October 9, 2020
• First Posted Date: October 14, 2020
• Last Update Posted Date: August 12, 2022
• Actual Study Start Date: February 25, 2021
• Estimated Primary Completion Date: December 23, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 9, 2020)

• 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) [ Time Frame: Up to approximately 34 months ]
  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.
• Overall Survival (OS) [ Time Frame: Up to approximately 44 months ]
  OS is defined as time from randomization to death due to any cause.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 9, 2020)

• 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) [ Time Frame: Up to approximately 24 months ]
  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.
• Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) [ Time Frame: Up to approximately 44 months ]
  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.
• Number of Participants Who Experienced One or More Adverse Events (AEs) [ Time Frame: Up to approximately 44 months ]
  An adverse event (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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
• Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) [ Time Frame: Up to approximately 44 months ]
  An adverse event (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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Belzutifan (MK-6482) in Combination With Lenvatinib Versus Cabozantinib for Treatment of Renal Cell Carcinoma (MK-6482-011)
• Official Title: An Open-label, Randomized, Phase 3 Study of MK-6482 in Combination With Lenvatinib (MK-7902) vs Cabozantinib in Participants With Advanced Renal Cell Carcinoma Who Have Progressed After Prior Anti-PD-1/L1 Therapy

Brief Summary

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

The primary hypothesis is that belzutifan + lenvatinib is superior to cabozantinib in terms of progression-free survival or overall survival.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Carcinoma, Renal Cell

Intervention

• Drug: Belzutifan
  Immediate-release 40 mg tablet
  Other Names:

  • PT2977
  • MK-6482
  • WELIREG™
• Drug: Lenvatinib
  Capsule available in 4 mg and 10 mg dosages
  Other Names:

  • Lenvima
  • E7080
  • MK-7902
• Drug: Cabozantinib
  Tablet available in 20 mg, 40 mg and 60 mg dosages
  Other Names:

  • Cabometyx
  • Cometriq
  • XL184
  • BMS-907351

Study Arms

• Experimental: Belzutifan + Lenvatinib
  Belzutifan 120 mg and lenvatinib 20 mg orally once a day
  Interventions:

  • Drug: Belzutifan
  • Drug: Lenvatinib
• Active Comparator: Cabozantinib
  Cabozantinib 60 mg orally once a day
  Intervention: Drug: Cabozantinib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 9, 2020): 708
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 23, 2024
• Estimated Primary Completion Date: December 23, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Unresectable, locally advanced or metastatic clear cell renal cell carcinoma (RCC).
• Disease progression on or after an anti-programmed cell death-1/ligand 1 (PD-1/L1) therapy as either first or second-line treatment for locally advanced/metastatic RCC or as adjuvant treatment with progression on or within 6 months of last dose.
• Measurable disease per RECIST 1.1 criteria as assessed by local study investigator.
• Karnofsky performance status (KPS) score of at least 70% assessed within 10 days before randomization.
• Received no more than 2 prior systemic regimens.
• Received only 1 prior antiPD-1/L1 therapy for adjuvant or locally advanced/metastatic RCC.
• A male participant is eligible to participate if he is abstinent from heterosexual intercourse or agrees to use contraception during the intervention period and for at least 7 days after the last dose of belzutifan or lenvatinib in the belzutifan+lenvatinib arm, whichever occurs last, and 23 days after the last dose of cabozantinib.
• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies: Not a woman of childbearing potential (WOCBP) or a WOCBP who agrees to follow the contraceptive guidance during the intervention period and for at least 30 days after the last dose of study intervention in the belzutifan+ lenvatinib arm, or 120 days after the last dose of study intervention in the cabozantinib arm.
• Adequately controlled blood pressure.
• Adequate organ function.

Exclusion Criteria:

• A pulse oximeter reading <92% at rest, requires intermittent supplemental oxygen, or requires chronic supplemental oxygen.
• Known additional malignancy that is progressing or has required active treatment within the past 3 years except for basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy.
• Known central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Clinically significant cardiac disease within 6 months of first dose of study intervention.
• Prolongation of QTc interval to >480 ms.
• Symptomatic pleural effusion (e.g.,cough, dyspnea, pleuritic chest pain) that is not clinically stable.
• Pre-existing ≥Grade 3 gastrointestinal or nongastrointestinal fistula.
• Moderate to severe hepatic impairment.
• History of significant bleeding within 3 months before randomization.
• History of solid organ transplantation.
• Known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study.
• Unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (e.g., gastrectomy, partial bowel obstruction, malabsorption).
• Known hypersensitivity or allergy to the active pharmaceutical ingredients or any component of the study intervention formulations.
• Received colony-stimulating factors [eg, granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GMCSF) or recombinant erythropoietin (EPO)] within 28 days before randomization.
• Prior treatment with belzutifan or another hypoxia-inducible factor (HIF)-2α inhibitor.
• Prior treatment with lenvatinib.
• Prior treatment with cabozantinib.
• Currently participating in a study of an investigational agent or using an investigational device.
• Active infection requiring systemic therapy.
• History of human immunodeficiency virus (HIV) infection.
• History of hepatitis B or known active hepatitis C infection.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Toll Free Number; 1-888-577-8839; Trialsites@merck.com

• Listed Location Countries: Australia, Austria, Belgium, Brazil, Canada, Chile, Colombia, Finland, France, Germany, Ireland, Italy, Japan, Korea, Republic of, Netherlands, Poland, Russian Federation, Spain, Switzerland, United Kingdom, United States

Administrative Information

• NCT Number: NCT04586231
• Other Study ID Numbers: 6482-011; MK-6482-011 ( Other Identifier: Merck ); jRCT2031210311 ( Other Identifier: jRCT(Japan Registry of Clinical Trials) ); 2020-002075-35 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

• Current Responsible Party: Merck Sharp & Dohme LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Merck Sharp & Dohme LLC
• Original Study Sponsor: Same as current
• Collaborators: Eisai Inc.

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme LLC

• PRS Account: Merck Sharp & Dohme LLC
• Verification Date: August 2022