Belzutifan Plus Fulvestrant in ER-Positive, HER2-Negative Unresectable Locally Advanced or Metastatic Breast Cancer

What is the Purpose of this Study?

This study focuses on people who have been diagnosed with estrogen receptor-positive (ER+)/HER2-negative breast cancer that cannot be removed surgically, has come back, or has spread to other areas of the body, and/or has grown after receiving hormone-blocking treatments. The purpose of the study is to evaluate the safety and effectiveness of the combination of 2 drugs, belzutifan (an experimental oral medication also known as MK-6482) plus fulvestrant in these patients. Researchers will compare belzutifan plus fulvestrant to everolimus (oral medication approved by the U.S. Food and Drug Administration) plus an endocrine therapy, either exemestane or fulvestrant (selected by the study doctor). Procedures include physical exam, imaging scans, blood and urine sample collection, tumor biopsies and drug administration. Participants will be randomly assigned to 1 of 2 groups. Group 1 will receive belzutifan plus fulvestrant. Group 2 will receive everolimus plus an endocrine therapy (fulvestrant or exemestane).

Eligibility

* 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

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

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Where can I participate?

CS Cancer at Beverly Hills : Nikki Kem-Bernard
CS Cancer at Cedars-Sinai Medical Center : Nikki Kem-Bernard

More about this Clinical Trial

What is the full name of this clinical trial?

MK-6482-029: 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 Metastatic Breast Cancer After Progression on Previous Endocrine Therapy

Study Details

Disease Type/Condition

Breast

Principal Investigator

Bitar, Jin Sun

Co-Investigators

Alice Chung, Armando Giuliano, Catherine Dang, Farin Amersi, Maryliza El-Masry, Philomena McAndrew, Scott Karlan, Yuan Yuan

Age Group

Adult

Phase

IRB Number

STUDY00003784

ClinicalTrials.gov ID

NCT06428396

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

Name

Nikki Kem-Bernard

Nikki.Bernard@cshs.org