study of belzutifan (mk-6482) plus fulvestrant for er+/her2- metastatic breast cancer (mk-6482-029/litespark-029)

Conditions: Metastatic Breast Cancer

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