Metastatic Breast Cancer
Conditions
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.
Interventions
DRUGBelzutifan
Belzutifan 120 mg administered QD as an oral tablet.
DRUGFulvestrant
Fulvestrant 500 mg administered as an IM injection.
DRUGEverolimus
Administered at 10mg via oral tablets QD.
DRUGExemestane
Administered at 25 mg via oral tablets QD.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | Up to approximately 29 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) at 6 months | Up to approximately 29 months | PFS data will be cumulated to a certain cut-off date and the analysis will be performed via Kaplan-Meier approach to estimate the PFS rate at 6 months using the entire PFS data up to the cut-off date. The cut-off date is event-driven and estimated to be approximately 28 months. |
| Progression-free Survival (PFS) at 12 months | Up to approximately 29 months | PFS data will be cumulated to a certain cut-off date and the analysis will be performed via Kaplan-Meier approach to estimate the PFS rate at 12 months using the entire PFS data up to the cut-off date. The cut-off date is event-driven and estimated to be approximately 28 months. |
| Overall Survival (OS) | Up to approximately 29 months | OS is defined as the time from randomization to death due to any cause. |
| Objective Response Rate (ORR) | Up to approximately 29 months | ORR is defined as the percentage of participants who have achieved confirmed Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by BICR. |
| Clinical Benefit Rate (CBR) | Up to approximately 29 months | CBR is defined as the percentage of participants who have CR: Disappearance of all target lesions, PR: At least a 30% decrease in the sum of diameters of target lesions, or stable disease (SD: Neither sufficient decrease to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study) for ≥24 weeks per RECIST 1.1 as assessed by BICR. |
| Number of Participants Who Experience an Adverse Event (AE) | Up to approximately 46 months | An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. |
| Number of Participants Who Discontinue Study Treatment Due To an AE | Up to approximately 46 months | An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. |
Countries
Argentina, Canada, Chile, Colombia, South Korea, Taiwan, Thailand, United Kingdom, United States
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed