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Combining belzutifan and fulvestrant for advanced breast cancer treatment

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)

Phase 2 Interventional Merck Sharp & Dohme LLC · NCT06428396

This study is testing if combining belzutifan with fulvestrant can help adults with advanced breast cancer who haven't had success with other treatments.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment120 (estimated)
Ages18 Years and up
SexAll
SponsorMerck Sharp & Dohme LLC Industry-sponsored
Drugs / interventionschemotherapy, radiation
Locations41 sites (Goodyear, Arizona and 40 other locations)
Trial IDNCT06428396 on ClinicalTrials.gov

What this trial studies

This study evaluates the effectiveness and safety of belzutifan (MK-6482) in combination with fulvestrant compared to everolimus plus endocrine therapy in adults with estrogen receptor-positive, HER2-negative metastatic breast cancer. Participants must have documented disease progression after previous endocrine therapy and meet specific eligibility criteria. The study aims to provide insights into alternative treatment options for patients with advanced breast cancer who have limited treatment options.

Who should consider this trial

Good fit: Ideal candidates are adults with ER+/HER2- metastatic breast cancer who have experienced disease progression after prior endocrine therapy.

Not a fit: Patients with HER2-positive breast cancer or those who have not received prior endocrine therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment combination could offer a new therapeutic option for patients with advanced breast cancer.

How similar studies have performed: Other studies have explored similar combinations in breast cancer treatment, showing promising results, but this specific combination is being evaluated for the first time.

Eligibility criteria

Show full inclusion / exclusion criteria 
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

Where this trial is running

Goodyear, Arizona and 40 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Metastatic Breast Cancer
Last reviewed 2026-06-14 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.