Fezolinetant for the Improvement of Vasomotor Symptoms in Breast Cancer Patients Taking Endocrine Therapy, VENT Trial

Inclusion Criteria:

• Female subject aged ≥ 18 years

• Taking endocrine therapy (tamoxifen, anastrozole, exemestane, or letrozole) foradjuvant treatment of stage 1-3 breast cancer or for chemoprevention (breast ductalcarcinoma in situ [DCIS] or high risk)

• Planning to take the same endocrine therapy for at least 10 weeks after study druginitiation

• Report 28 or more VMS episodes, at least some of which are severe or bothersome,during the 7-day screening period

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2 x upperlimit of normal (ULN) within 28 days prior to randomization

• Total bilirubin < 2 x ULN within 28 days prior to randomization

• Completion of chemotherapy, if given. Concurrent use of gonadotropin releasinghormone agonist (GnRHa) therapy, anti-HER2 therapy, bisphosphonate therapy, polyadenosine diphosphate-ribose polymerase (PARP) inhibitor therapy, and abemaciclibtherapy is permitted

• Patients receiving treatment with selective serotonin reuptake inhibitor (SSRIs),serotonin and norepinephrine reuptake inhibitor (SNRIs), gabapentinoids, clonidine,or oxybutynin must have been taking a stable dose for at least 30 days prior toenrollment if they plan to continue the drug during study participation, and willingto remain on the treatment for the duration of study participation. If they do notplan to take the medication during study participation, they should stop themedication at least 7 days before the start of the VMS screening period

• Patients taking over-the-counter supplements or herbal medications for treatment ofVMS must stop the medication at least 7 days before the start of the VMS screeningperiod

• Able to self-complete questionnaires in English

• Able to provide informed consent and willing to sign an approved consent form thatconforms to federal and institutional guidelines

• For women of childbearing potential, participants must agree to use an effectivecontraceptive method during protocol therapy and for 3 months following completionof protocol therapy with details provided as a part of the consent process and musthave a negative pregnancy test at screening. In addition to routine contraceptivemethods, "effective contraception" also includes refraining from sexual activitythat might result in pregnancy and surgery intended to prevent pregnancy (or with aside-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy,and bilateral tubal ligation/occlusion

Exclusion Criteria:

• Metastatic breast cancer

• Prior treatment with fezolinetant

• Known severe renal disease (estimated glomerular filtration rate [eGFR] less than 30mL/min/1.73 m^2)

• Known cirrhosis

• Pregnant or breast feeding, or plan to become pregnant during the study period orwithin 3 months of completing study medication

• Concomitant use of CYP1A2 inhibitors, including but not limited to fluvoxamine,ciprofloxacin, cimetidine, citalopram, and ribociclib

• Concomitant use of systemic or transdermal estrogen products

• Known allergy or hypersensitivity to fezolinetant or any of the excipients in themedication

• Unable to take oral medications

• Any medical condition that would interfere with the absorption of study medication.Prior gastric bypass is permitted

• Concurrent medical disease that could confound or interfere with evaluation of VMS

• Patients with a prior or concurrent malignancy whose natural history or treatment,in the opinion of the treating investigator, has the potential to interfere with thesafety or efficacy assessment of the investigational regimen

• Patients who are participating concurrently in another interventional study (actually receiving a study medication) or participated in an interventional studywithin 30 days prior to screening or received any investigational drug within 30days or within 5 half-lives prior to screening, whichever is longer