Study of Belzutifan (MK-6482) Plus Fulvestrant for ER+/HER2- Metastatic Breast Cancer (MK-6482-029/LITESPARK-029)

May 14, 2026 updated by: Merck Sharp & Dohme LLC

A Phase 2, Randomized, Active-controlled, Open-label, Multicenter Study of Belzutifan Plus Fulvestrant in Participants With Estrogen Receptor Positive, HER2 Negative Unresectable Locally Advanced or Metastic Breast Cancer After Progression on Previous Endocrine Therapy (LITESPARK-029)

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

120

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Argentina
      • Córdoba, Argentina, X5004BAL
        • Recruiting
        • Hospital Italiano de Córdoba ( Site 0508)
        • Contact:
          • Study Coordinator
          • Phone Number: +543514106500
    • Buenos Aires
      • CABA, Buenos Aires, Argentina, C1056ABI
        • Recruiting
        • Centro de Investigaciones Metabólicas (CINME)-Oncology ( Site 0504)
        • Contact:
          • Study Coordinator
          • Phone Number: +5408003450697
      • Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina, C1280AEB
        • Recruiting
        • Hospital Británico de Buenos Aires-Oncology ( Site 0500)
        • Contact:
          • Study Coordinator
          • Phone Number: 54911563819972
      • Mar del Plata, Buenos Aires, Argentina, B7600FZO
        • Recruiting
        • Instituto de Investigaciones Clínicas Mar del Plata ( Site 0502)
        • Contact:
          • Study Coordinator
          • Phone Number: +542234963224
    • Buenos Aires F.D.
      • Buenos Aires, Buenos Aires F.D., Argentina, C1426ANZ
        • Recruiting
        • Instituto Alexander Fleming-Alexander Fleming ( Site 0505)
        • Contact:
          • Study Coordinator
          • Phone Number: +5491138850425
    • Córdoba Province
      • Córdoba, Córdoba Province, Argentina, 5000
        • Recruiting
        • Sanatorio Allende - Cerro-Oncology ( Site 0506)
        • Contact:
          • Study Coordinator
          • Phone Number: +5403514269200E1661
    • Santa Fe Province
      • Rosario, Santa Fe Province, Argentina, S2000KZE
        • Recruiting
        • Instituto de Oncología de Rosario ( Site 0501)
        • Contact:
          • Study Coordinator
          • Phone Number: +54 341 4218909
  • Canada
    • Quebec
      • Montreal, Quebec, Canada, H3T 1E2
        • Recruiting
        • Jewish General Hospital ( Site 0400)
        • Contact:
          • Study Coordinator
          • Phone Number: 5143408222
  • Chile
    • Maule Region
      • Talca, Maule Region, Chile, 3460000
        • Recruiting
        • Centro de Investigación del Maule ( Site 4106)
        • Contact:
          • Study Coordinator
          • Phone Number: +56712981241
    • Region M. de Santiago
      • Santiago, Region M. de Santiago, Chile, 7500921
        • Recruiting
        • FALP ( Site 4102)
        • Contact:
          • Study Coordinator
          • Phone Number: +56224205098
      • Santiago, Region M. de Santiago, Chile, 8330024
        • Recruiting
        • Pontificia Universidad Catolica de Chile ( Site 4108)
        • Contact:
          • Study Coordinator
          • Phone Number: +56934331806
      • Santiago, Region M. de Santiago, Chile, 8420383
        • Recruiting
        • Bradfordhill ( Site 4100)
        • Contact:
          • Study Coordinator
          • Phone Number: +56229490970
  • Colombia
    • Departamento de Córdoba
      • Montería, Departamento de Córdoba, Colombia, 230002
        • Recruiting
        • IMAT S.A.S ( Site 1205)
        • Contact:
          • Study Coordinator
          • Phone Number: +57 3205669416
    • Risaralda Department
      • Pereira, Risaralda Department, Colombia, 660001
        • Recruiting
        • Oncologos Del Occidente ( Site 1200)
        • Contact:
          • Study Coordinator
          • Phone Number: +573187715522
    • Valle del Cauca Department
      • Cali, Valle del Cauca Department, Colombia, 760032
        • Recruiting
        • Fundacion Valle del Lili ( Site 1204)
        • Contact:
          • Study Coordinator
          • Phone Number: +57 3162801914
  • South Korea
      • Seoul, South Korea, 03080
        • Recruiting
        • Seoul National University Hospital ( Site 3100)
        • Contact:
          • Study Coordinator
          • Phone Number: +82220720850
      • Seoul, South Korea, 06351
        • Recruiting
        • Samsung Medical Center ( Site 3101)
        • Contact:
          • Study Coordinator
          • Phone Number: +82220720381
  • Taiwan
      • Tainan, Taiwan, 704302
        • Recruiting
        • National Cheng Kung University Hospital ( Site 3300)
        • Contact:
          • Study Coordinator
          • Phone Number: +88662353535x4273
      • Taipei, Taiwan, 106
        • Recruiting
        • National Taiwan University Cancer Center ( Site 3302)
        • Contact:
          • Study Coordinator
          • Phone Number: +886-2-2322-0322
      • Taipei, Taiwan, 10002
        • Recruiting
        • National Taiwan University Hospital ( Site 3301)
        • Contact:
          • Study Coordinator
          • Phone Number: +886-2-2312-3456
  • Thailand
    • Bangkok
      • Bangkoknoi, Bangkok, Thailand, 10700
        • Recruiting
        • Faculty of Medicine Siriraj Hospital ( Site 3500)
        • Contact:
          • Study Coordinator
          • Phone Number: +6624194489
    • Changwat Khon Kaen
      • Muang, Changwat Khon Kaen, Thailand, 40002
        • Recruiting
        • Faculty of Medicine - Khon Kaen University ( Site 3502)
        • Contact:
          • Study Coordinator
          • Phone Number: +6643363746
    • Changwat Songkhla
      • Hat Yai, Changwat Songkhla, Thailand, 90110
        • Recruiting
        • Songklanagarind Hospital ( Site 3501)
        • Contact:
          • Study Coordinator
          • Phone Number: +6674451469
  • United Kingdom
    • England
      • Truro, England, United Kingdom, TR1 3LJ
        • Recruiting
        • The Royal Cornwall Hospital ( Site 1904)
        • Contact:
          • Study Coordinator
          • Phone Number: 441872258307
    • London, City of
      • London, London, City of, United Kingdom, EC1A 7BE
        • Recruiting
        • St Bartholomews Hospital ( Site 1900)
        • Contact:
          • Study Coordinator
          • Phone Number: 0203 765 8609
    • Manchester
      • Withington, Manchester, United Kingdom, M20 4BX
        • Recruiting
        • The Christie Hospital NHS Foundation Trust ( Site 1902)
        • Contact:
          • Study Coordinator
          • Phone Number: +441614463000
    • Suffolk
      • Ipswich, Suffolk, United Kingdom, IP4 5PD
        • Recruiting
        • Ipswich Hospital ( Site 1911)
        • Contact:
          • Study Coordinator
          • Phone Number: +4401473704389
  • United States
    • Arizona
      • Goodyear, Arizona, United States, 85338
        • Recruiting
        • City of Hope - Phoenix ( Site 0006)
        • Contact:
          • Study Coordinator
          • Phone Number: 623-207-3000
    • California
      • Beverly Hills, California, United States, 90211
        • Recruiting
        • Cedars Sinai Medical Center ( Site 0012)
        • Contact:
          • Study Coordinator
          • Phone Number: 310-423-3277
      • La Jolla, California, United States, 92093
        • Recruiting
        • Moores Cancer Center at UC San Diego Health ( Site 0025)
        • Contact:
          • Study Coordinator
          • Phone Number: 858-822-5366
      • Los Angeles, California, United States, 90033
        • Active, not recruiting
        • USC/Norris Comprehensive Cancer Center ( Site 0013)
      • Newport Beach, California, United States, 92663
        • Recruiting
        • USC Norris Oncology Hematology Newport Beach ( Site 0029)
        • Contact:
          • Study Coordinator
          • Phone Number: 323-865-3000
    • Georgia
      • Marietta, Georgia, United States, 30060
        • Completed
        • Northwest Georgia Oncology Centers, a Service of Wellstar Cobb Hospital ( Site 0011)
      • Newnan, Georgia, United States, 30265
        • Completed
        • Southeastern Regional Medical Center ( Site 0010)
    • Louisiana
      • Shreveport, Louisiana, United States, 71105
        • Completed
        • CHRISTUS Highland ( Site 0005)
    • Nevada
      • Reno, Nevada, United States, 89502
        • Recruiting
        • Renown Regional Medical Center ( Site 0018)
        • Contact:
          • Study Coordinator
          • Phone Number: 775-982-3890
    • New Jersey
      • Camden, New Jersey, United States, 08103
        • Recruiting
        • MD Anderson Cancer Center at Cooper ( Site 0024)
        • Contact:
          • Study Coordinator
          • Phone Number: 856-342-2000
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • MD Anderson ( Site 0015)
        • Contact:
          • Study Coordinator
          • Phone Number: 713-792-2848
      • San Antonio, Texas, United States, 78229
        • Recruiting
        • Mays Cancer Center ( Site 0022)
        • Contact:
          • Study Coordinator
          • Phone Number: 210-450-1000
    • Wisconsin
      • Madison, Wisconsin, United States, 53715
        • Recruiting
        • SSM Health Dean Medical Group - South Madison Campus Health Research/Circuit Clinical ( Site 0034)
        • Contact:
          • Study Coordinator
          • Phone Number: 608-410-2767
      • Milwaukee, Wisconsin, United States, 53226
        • Recruiting
        • Medical College of Wisconsin - Froedtert Hospital ( Site 0014)
        • Contact:
          • Study Coordinator
          • Phone Number: 414-805-0791

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival (PFS)
Time Frame: Up to approximately 29 months
PFS is defined as the time from randomization to the first documented disease progression per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) based on blinded independent central review (BICR) or death due to any cause, whichever occurs first.
Up to approximately 29 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival (PFS) at 6 months
Time Frame: Up to approximately 29 months
PFS data will be cumulated to a certain cut-off date and the analysis will be performed via Kaplan-Meier approach to estimate the PFS rate at 6 months using the entire PFS data up to the cut-off date. The cut-off date is event-driven and estimated to be approximately 28 months.
Up to approximately 29 months
Progression-free Survival (PFS) at 12 months
Time Frame: Up to approximately 29 months
PFS data will be cumulated to a certain cut-off date and the analysis will be performed via Kaplan-Meier approach to estimate the PFS rate at 12 months using the entire PFS data up to the cut-off date. The cut-off date is event-driven and estimated to be approximately 28 months.
Up to approximately 29 months
Overall Survival (OS)
Time Frame: Up to approximately 29 months
OS is defined as the time from randomization to death due to any cause.
Up to approximately 29 months
Objective Response Rate (ORR)
Time Frame: Up to approximately 29 months
ORR is defined as the percentage of participants who have achieved confirmed 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 as assessed by BICR.
Up to approximately 29 months
Clinical Benefit Rate (CBR)
Time Frame: Up to approximately 29 months
CBR is defined as the percentage of participants who have CR: Disappearance of all target lesions, 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) for ≥24 weeks per RECIST 1.1 as assessed by BICR.
Up to approximately 29 months
Number of Participants Who Experience an Adverse Event (AE)
Time Frame: Up to approximately 46 months
An AE was 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 could therefore have been 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.
Up to approximately 46 months
Number of Participants Who Discontinue Study Treatment Due To an AE
Time Frame: Up to approximately 46 months
An AE was 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 could therefore have been 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.
Up to approximately 46 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck Sharp & Dohme LLC

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 27, 2024

Primary Completion (Estimated)

May 5, 2027

Study Completion (Estimated)

December 25, 2028

Study Registration Dates

First Submitted

May 20, 2024

First Submitted That Met QC Criteria

May 20, 2024

First Posted (Actual)

May 24, 2024

Study Record Updates

Last Update Posted (Actual)

May 18, 2026

Last Update Submitted That Met QC Criteria

May 14, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 6482-029
  • MK-6482-029 (Other Identifier: MSD)
  • LITESPARK-029 (Other Identifier: MSD)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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