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

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

NCT ID: NCT06428396

Condition: Metastatic Breast Cancer

Conditions: Official terms:
Breast Neoplasms
Everolimus
Fulvestrant
Exemestane
Belzutifan

Study type: Interventional

Study phase: Phase 2

Overall status: Recruiting

Study design:

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Belzutifan
Description: Belzutifan 120 mg administered QD as an oral tablet.
Arm group label: Belzutifan + Fulvestrant

Other name: MK-6482

Intervention type: Drug
Intervention name: Fulvestrant
Description: Fulvestrant 500 mg administered as an IM injection.
Arm group label: Belzutifan + Fulvestrant
Arm group label: Everolimus + ET (fulvestrant or exemestane)

Intervention type: Drug
Intervention name: Everolimus
Description: Administered at 10mg via oral tablets QD.
Arm group label: Everolimus + ET (fulvestrant or exemestane)

Intervention type: Drug
Intervention name: Exemestane
Description: Administered at 25 mg via oral tablets QD.
Arm group label: Everolimus + ET (fulvestrant or exemestane)

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.

Criteria for eligibility:
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

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

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

Address:
City: Marietta
Zip: 30060
Country: United States

Status: Recruiting

Contact:
Last name: Study Coordinator

Phone: 770-281-5100

Facility:
Name: Renown Regional Medical Center ( Site 0018)

Address:
City: Reno
Zip: 89502
Country: United States

Status: Recruiting

Contact:
Last name: Study Coordinator

Phone: 775-982-3890

Facility:
Name: Seoul National University Hospital ( Site 3100)

Address:
City: Seoul
Zip: 03080
Country: Korea, Republic of

Status: Recruiting

Contact:
Last name: Study Coordinator

Phone: 02-2072-0850

Start date: October 30, 2024

Completion date: October 7, 2028

Lead sponsor:
Agency: Merck Sharp & Dohme LLC
Agency class: Industry

Source: Merck Sharp & Dohme LLC

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06428396
https://www.merckclinicaltrials.com/