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Purpose

The purpose of this study is to assess the efficacy and safety of belzutifan (MK-6482) plus fulvestrant compared to everolimus plus endocrine therapy (ET) (investigator's choice of fulvestrant or exemestane) in adults with estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) unresectable metastatic breast cancer. There is no formal hypothesis testing in this study.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Has a diagnosis of estrogen receptor positive (ER+)/human epidermal growth factor receptor negative (HER2-) invasive breast carcinoma that is either locally advanced disease not amenable to resection or metastatic disease not treatable with curative intent - Has documented radiographic confirmation of disease progression during or after the last administered endocrine therapy (ET) - Provides additional tissue from the same sample used to determine ER and HER2 status locally - Has received ET in the noncurative setting and has 1) Radiographic disease progression on 12 months or more of ET in combination with CDK4/6 inhibitor in the noncurative setting or 2) Received at least 2 lines of ET in the noncurative setting including CDK4/6 inhibitor where the CDK 4/6 inhibitor was discontinued due to intolerance - Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed within 7 days of randomization - Participants who have AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline. Participants with endocrine-related AEs who are adequately treated with hormone replacement or participants who have ≤Grade 2 neuropathy are eligible - Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks prior to the first dose of study intervention and have undetectable HBV viral load prior to randomization

Exclusion Criteria

  • Has Breast cancer amenable to treatment with curative intent - Is unable to receive any of the endocrine therapies (ETs) (ie, fulvestrant or exemestane) - Has known difficulty in tolerating oral medications, unable to swallow orally administered medication, or conditions which would impair absorption of oral medications such as uncontrolled nausea or vomiting (ie, CTCAE =Grade 3 despite antiemetic therapy), ongoing gastrointestinal obstruction, motility disorder, malabsorption syndrome, or prior gastric bypass - Has advanced/metastatic, symptomatic visceral spread at risk of rapidly evolving into life-threatening complications - Has active, bleeding diathesis, or on oral anti-vitamin K medication - Has history of noninfectious pneumonitis/interstitial lung disease including radiation pneumonitis that required steroids or has current pneumonitis/interstitial lung disease - Has a known germline BRCA mutation (deleterious or suspected deleterious) and has received previous treatment with poly-ADP ribose polymerase (PARP) inhibition either in the adjuvant or metastatic setting - Has received prior fulvestrant in the adjuvant, unresectable locally advanced, or metastatic setting - Has received any line of cytotoxic chemotherapy or PARP inhibitor in the unresectable or noncurative advanced/metastatic setting - Has received prior radiotherapy for non-central nervous system (CNS) disease or required corticosteroids for radiation-related toxicities including radiation pneumonitis, within 14 days of the first dose of study intervention - Is currently receiving either a strong inhibitor or inducer of CYP3A4 that cannot be discontinued for the duration of the study - Has received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization - Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention - Has concurrent active Hepatitis B and Hepatitis C virus infection - Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months from Day 1 of study medication administration, or New York Heart Association Class III or Class IV congestive heart failure - Has not adequately recovered from major surgery or have ongoing surgical complications

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Belzutifan + Fulvestrant 		Participants will receive belzutifan 120 mg orally once daily (QD) PLUS fulvestrant 500 mg via intramuscular (IM) injection on Days 1 and 15 of Cycle 1, and Day 1 of each 28-day cycle thereafter until progressive disease or discontinuation.
  • Drug: Belzutifan
    Belzutifan 120 mg administered QD as an oral tablet.
    Other names:
    • MK-6482
  • Drug: Fulvestrant
    Fulvestrant 500 mg administered as an IM injection.
Active Comparator
Everolimus + ET (fulvestrant or exemestane) 		Participants will receive everolimus 10 mg orally QD PLUS investigator's choice of fulvestrant 500 mg via IM injection on Days 1 and 15 of Cycle 1, and Day 1 of each 28-day cycle thereafter OR exemestane 25 mg orally QD until progressive disease or discontinuation.
  • Drug: Fulvestrant
    Fulvestrant 500 mg administered as an IM injection.
  • Drug: Everolimus
    Administered at 10mg via oral tablets QD.
  • Drug: Exemestane
    Administered at 25 mg via oral tablets QD.

Recruiting Locations

Mays Cancer Center ( Site 0022)
San Antonio, Texas 78229
Contact:
Study Coordinator
210-450-1000

More Details

Status
Recruiting
Sponsor
Merck Sharp & Dohme LLC

Study Contact

Toll Free Number
1-888-577-8839
Trialsites@msd.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.