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

Launched by MERCK SHARP & DOHME LLC · May 20, 2024

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment option for people with a specific type of metastatic breast cancer, known as estrogen receptor-positive and human epidermal growth factor receptor 2-negative (ER+/HER2-). The researchers want to see how well the drug belzutifan (MK-6482) works when combined with fulvestrant compared to another treatment that includes everolimus and an endocrine therapy of the doctor's choice. To be eligible for the trial, participants should have advanced breast cancer that cannot be surgically removed and have experienced disease progression after prior endocrine therapy. They should also be in good health overall, with a performance status indicating they can carry out daily activities.

If someone joins the trial, they will receive one of the two treatment options and will be closely monitored for safety and how well the treatments are working. It's important to note that there are specific health conditions and treatment histories that could make someone ineligible, such as having received certain prior therapies or having certain medical issues. This study is currently looking for participants aged 65 and older, and both men and women can take part. Overall, this trial aims to find more effective treatment options for those facing this challenging disease.

Gender

ALL

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