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

NCT06428396 | Recruiting Phase 2 FDA Drug

• 3 other identifiers: 6482-029MK-6482-029LITESPARK-029
• Study Type: interventional
• Target: 120
• Locations: 9 countries
• Sites: 41

Brief Summary

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.

Conditions

Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS)

  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 Outcomes (7)

• Progression-free Survival (PFS) at 6 months

  Up to approximately 29 months

• Progression-free Survival (PFS) at 12 months

  Up to approximately 29 months

• Overall Survival (OS)

  Up to approximately 29 months

• Objective Response Rate (ORR)

  Up to approximately 29 months

• Clinical Benefit Rate (CBR)

  Up to approximately 29 months

Study Arms (2)

Belzutifan + Fulvestrant

EXPERIMENTAL

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; Drug: Fulvestrant

Everolimus + ET (fulvestrant or exemestane)

ACTIVE COMPARATOR

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; Drug: Everolimus; Drug: Exemestane

Interventions

Belzutifan DRUG

Belzutifan 120 mg administered QD as an oral tablet.

Also known as: MK-6482

Belzutifan + Fulvestrant

Fulvestrant DRUG

Fulvestrant 500 mg administered as an IM injection.

Belzutifan + Fulvestrant; Everolimus + ET (fulvestrant or exemestane)

Everolimus DRUG

Administered at 10mg via oral tablets QD.

Everolimus + ET (fulvestrant or exemestane)

Exemestane DRUG

Administered at 25 mg via oral tablets QD.

Everolimus + ET (fulvestrant or exemestane)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (41)

City of Hope - Phoenix ( Site 0006)

Goodyear, Arizona, 85338, United States

RECRUITING

Cedars Sinai Medical Center ( Site 0012)

Beverly Hills, California, 90211, United States

RECRUITING

Moores Cancer Center at UC San Diego Health ( Site 0025)

La Jolla, California, 92093, United States

RECRUITING

USC/Norris Comprehensive Cancer Center ( Site 0013)

Los Angeles, California, 90033, United States

ACTIVE NOT RECRUITING

USC Norris Oncology Hematology Newport Beach ( Site 0029)

Newport Beach, California, 92663, United States

RECRUITING

Northwest Georgia Oncology Centers, a Service of Wellstar Cobb Hospital ( Site 0011)

Marietta, Georgia, 30060, United States

COMPLETED

Southeastern Regional Medical Center ( Site 0010)

Newnan, Georgia, 30265, United States

RECRUITING

CHRISTUS Highland ( Site 0005)

Shreveport, Louisiana, 71105, United States

COMPLETED

Renown Regional Medical Center ( Site 0018)

Reno, Nevada, 89502, United States

RECRUITING

MD Anderson Cancer Center at Cooper ( Site 0024)

Camden, New Jersey, 08103, United States

RECRUITING

MD Anderson ( Site 0015)

Houston, Texas, 77030, United States

RECRUITING

Mays Cancer Center ( Site 0022)

San Antonio, Texas, 78229, United States

RECRUITING

SSM Health Dean Medical Group - South Madison Campus Health Research/Circuit Clinical ( Site 0034)

Madison, Wisconsin, 53715, United States

RECRUITING

Medical College of Wisconsin - Froedtert Hospital ( Site 0014)

Milwaukee, Wisconsin, 53226, United States

RECRUITING

Centro de Investigaciones Metabólicas (CINME)-Oncology ( Site 0504)

CABA, Buenos Aires, C1056ABI, Argentina

RECRUITING

Hospital Británico de Buenos Aires-Oncology ( Site 0500)

Ciudad Autónoma de Buenos Aires, Buenos Aires, C1280AEB, Argentina

RECRUITING

Instituto de Investigaciones Clínicas Mar del Plata ( Site 0502)

Mar del Plata, Buenos Aires, B7600FZO, Argentina

RECRUITING

Instituto Alexander Fleming-Alexander Fleming ( Site 0505)

Buenos Aires, Buenos Aires F.D., C1426ANZ, Argentina

RECRUITING

Sanatorio Allende - Cerro-Oncology ( Site 0506)

Córdoba, Córdoba Province, 5000, Argentina

RECRUITING

Instituto de Oncología de Rosario ( Site 0501)

Rosario, Santa Fe Province, S2000KZE, Argentina

RECRUITING

Hospital Italiano de Córdoba ( Site 0508)

Córdoba, X5004BAL, Argentina

RECRUITING

Jewish General Hospital ( Site 0400)

Montreal, Quebec, H3T 1E2, Canada

RECRUITING

Centro de Investigación del Maule ( Site 4106)

Talca, Maule Region, 3460000, Chile

RECRUITING

FALP ( Site 4102)

Santiago, Region M. de Santiago, 7500921, Chile

RECRUITING

Pontificia Universidad Catolica de Chile ( Site 4108)

Santiago, Region M. de Santiago, 8330024, Chile

RECRUITING

Bradfordhill ( Site 4100)

Santiago, Region M. de Santiago, 8420383, Chile

RECRUITING

IMAT S.A.S ( Site 1205)

Montería, Departamento de Córdoba, 230002, Colombia

RECRUITING

Oncologos Del Occidente ( Site 1200)

Pereira, Risaralda Department, 660001, Colombia

RECRUITING

Fundacion Valle del Lili ( Site 1204)

Cali, Valle del Cauca Department, 760032, Colombia

RECRUITING

Seoul National University Hospital ( Site 3100)

Seoul, 03080, South Korea

RECRUITING

Samsung Medical Center ( Site 3101)

Seoul, 06351, South Korea

RECRUITING

National Cheng Kung University Hospital ( Site 3300)

Tainan, 704302, Taiwan

RECRUITING

National Taiwan University Hospital ( Site 3301)

Taipei, 10002, Taiwan

RECRUITING

National Taiwan University Cancer Center ( Site 3302)

Taipei, 106, Taiwan

RECRUITING

Faculty of Medicine Siriraj Hospital ( Site 3500)

Bangkoknoi, Bangkok, 10700, Thailand

RECRUITING

Faculty of Medicine - Khon Kaen University ( Site 3502)

Muang, Changwat Khon Kaen, 40002, Thailand

RECRUITING

Songklanagarind Hospital ( Site 3501)

Hat Yai, Changwat Songkhla, 90110, Thailand

RECRUITING

The Royal Cornwall Hospital ( Site 1904)

Truro, England, TR1 3LJ, United Kingdom

RECRUITING

St Bartholomews Hospital ( Site 1900)

London, London, City of, EC1A 7BE, United Kingdom

RECRUITING

The Christie Hospital NHS Foundation Trust ( Site 1902)

Withington, Manchester, M20 4BX, United Kingdom

RECRUITING

Ipswich Hospital ( Site 1911)

Ipswich, Suffolk, IP4 5PD, United Kingdom

RECRUITING

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

Breast Neoplasms

Interventions

belzutifan; Fulvestrant; Everolimus; exemestane

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Central Study Contacts

Toll Free Number

CONTACT

1-888-577-8839; Trialsites@msd.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 20, 2024
• First Posted: May 24, 2024
• Study Start: November 27, 2024
• Primary Completion (Estimated): May 5, 2027
• Study Completion (Estimated): October 7, 2028
• Last Updated: April 24, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

TH (3); CL (4); TW (3); GB (4); CO (3); AR (7); US (14); CA (1); KR (2)