Clinical trial NCT06428396: Study of Belzutifan (MK-6482) Plus Fulvestrant for ER+/HER2- Metastatic Breast Cancer (MK-6482-029/LITESPARK-029)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Metastatic Breast Cancer
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2024-05-24
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: Up to approximately 29 months
Secondary outcomes:
measure: Progression-free Survival (PFS) at 6 months
timeFrame: Up to approximately 29 months
measure: Progression-free Survival (PFS) at 12 months
timeFrame: Up to approximately 29 months
measure: Overall Survival (OS)
timeFrame: Up to approximately 29 months
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 29 months
measure: Clinical Benefit Rate (CBR)
timeFrame: Up to approximately 29 months
measure: Number of Participants Who Experience an Adverse Event (AE)
timeFrame: Up to approximately 46 months
measure: Number of Participants Who Discontinue Study Treatment Due To an AE
timeFrame: Up to approximately 46 months
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Cedars Sinai Medical Center ( Site 0012)
state: California
city: La Jolla
country: United States
facility: Moores Cancer Center at UC San Diego Health ( Site 0025)
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center ( Site 0013)
state: California
city: Newport Beach
country: United States
facility: USC Norris Oncology Hematology Newport Beach ( Site 0029)
state: California
city: Marietta
country: United States
facility: Northwest Georgia Oncology Centers, a Service of Wellstar Cobb Hospital ( Site 0011)
state: Georgia
city: Shreveport
country: United States
facility: CHRISTUS Highland ( Site 0005)
state: Louisiana
city: Reno
country: United States
facility: Renown Regional Medical Center ( Site 0018)
state: Nevada
city: San Antonio
country: United States
facility: Mays Cancer Center ( Site 0022)
state: Texas
city: Caba
country: Argentina
facility: Centro de Investigaciones Metabólicas (CINME)-Oncology ( Site 0504)
state: Buenos Aires
city: Ciudad autónoma de Buenos Aires
country: Argentina
facility: Hospital Británico de Buenos Aires-Oncology ( Site 0500)
state: Buenos Aires
city: Mar del Plata
country: Argentina
facility: Instituto de Investigaciones Clínicas Mar del Plata ( Site 0502)
state: Buenos Aires
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: Instituto Alexander Fleming-Alexander Fleming ( Site 0505)
state: Caba
city: Córdoba
country: Argentina
facility: Sanatorio Allende - Cerro-Oncology ( Site 0506)
state: Cordoba
city: Rosario
country: Argentina
facility: Instituto de Oncología de Rosario ( Site 0501)
state: Santa Fe
city: Montreal
country: Canada
facility: Jewish General Hospital ( Site 0400)
state: Quebec
city: Talca
country: Chile
facility: Centro de Investigación del Maule ( Site 4106)
state: Maule
city: Santiago.
country: Chile
facility: Bradfordhill ( Site 4100)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: FALP ( Site 4102)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Pontificia Universidad Catolica de Chile ( Site 4108)
state: Region M. De Santiago
city: Monteria
country: Colombia
facility: IMAT S.A.S ( Site 1205)
state: Cordoba
city: Pereira
country: Colombia
facility: Oncologos Del Occidente ( Site 1200)
state: Risaralda
city: Cali
country: Colombia
facility: Fundacion Valle del Lili ( Site 1204)
state: Valle Del Cauca
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital ( Site 3100)
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center ( Site 3101)
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital ( Site 3300)
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital ( Site 3301)
city: Taipei
country: Taiwan
facility: National Taiwan University Cancer Center ( Site 3302)
city: Muang
country: Thailand
facility: Faculty of Medicine - Khon Kaen University ( Site 3502)
state: Khon Kaen
city: Bangkoknoi
country: Thailand
facility: Faculty of Medicine Siriraj Hospital ( Site 3500)
state: Krung Thep Maha Nakhon
city: Hat Yai
country: Thailand
facility: Songklanagarind Hospital ( Site 3501)
state: Songkhla
city: Truro
country: United Kingdom
facility: The Royal Cornwall Hospital ( Site 1904)
state: England
city: London
country: United Kingdom
facility: St Bartholomews Hospital ( Site 1900)
state: London, City Of
city: Withington
country: United Kingdom
facility: The Christie Hospital NHS Foundation Trust ( Site 1902)
state: Manchester
city: Ipswich
country: United Kingdom
facility: Ipswich Hospital ( Site 1911)
state: Suffolk
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: