A Study to Confirm if Fezolinetant Helps Reduce Hot Flashes in Women With Breast Cancer Who Are Having Hormone Therapy

Inclusion Criteria:

• Participant has a personal history of stage 0-3 hormone receptor positive (HR+),either human epidermal growth factor receptor (HER)-2+ or HER-2- breast cancer;appropriate documentation includes a written or electronic report.

• Participant must be receiving stable maintenance adjuvant endocrine therapy (tamoxifen 20 mg daily or aromatase inhibitors, such as anastrozole, letrozole andexemestane) with or without gonadotropin-releasing hormone (GnRH)agonists/antagonists for a minimum of 4 months and be planning to continue onadjuvant endocrine therapy for the duration of the trial without change to therapy,brand or dose. Add-on therapies for breast cancer adjuvant treatment (e.g., cyclindependent kinase-4 (CDK4) inhibitors) are allowed.

• Participant has a minimum average of 7 moderate to severe hot flashes (HFs) (vasomotor symptoms (VMS)) per day as recorded in the electronic daily diary (datamust be available for at least 7 of the last 10 days prior to randomization).

• Has an European Cooperative Oncology Group (ECOG) score 0 or 1.

• Has at least 12-month life expectation.

• Participant is born female.

• Female participant: Is not pregnant and at least 1 of the following conditionsapply:

• Not a woman of childbearing potential (WOCBP)

• WOCBP who has a negative urine or serum pregnancy test at screening and day 1and agrees to follow the contraceptive guidance from the time of informedconsent through at least 30 days after final investigational study interventionadministration.

• Female participant: Must not be breastfeeding or lactating starting at screening andwhile the participant is taking investigational study intervention and for 30 daysafter final investigational study intervention administration.

• Female participant: Must not donate ova starting at first administration of studyintervention and while the participant is taking investigational study interventionand for 30 days after final investigational study intervention administration.

• Participant agrees not to participate in another interventional study whileparticipating in the present study until the end of the 1-year extension follow-upperiod.

• Participant's condition is stable as determined on the basis of medical history andgeneral physical examination (including a bimanual clinical pelvic examinationdevoid of relevant clinical findings performed at the screening visit), hematologyand biochemistry parameters, pulse rate and/or blood pressure and electrocardiogram (ECG) (or showing no clinically relevant deviations obtained within the last 3months or at screening).

• Participant has no new clinically significant findings on breast examination or fromimaging (mammogram or breast ultrasound). Results indicate that the participant is agood candidate for the study. Appropriate documentation includes a written orelectronic report. In case of double mastectomy, imaging is not needed.

• Participant has a negative serology panel (including hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody and human immunodeficiency virus (HIV)antibody screens).

Exclusion Criteria:

• Participant has diagnosis of metastatic breast cancer (stage 4).

• Participant has current or history (except complete remission for 5 years or moreprior to signing informed consent) of any malignancy except for HR+ breast cancer (stage 0 to 3) or basal cell carcinoma.

• Participant has had surgery or non-surgical (chemotherapy or radiotherapy) treatmentfor breast cancer within the last 3 months prior to signing informed consent.

• Participant has active liver disease, jaundice, or elevated liver aminotransferases (alanine aminotransferase (ALT) or aspartate aminotransferase (AST)), elevated totalbilirubin (TBL) or direct bilirubin (DBL), or elevated alkaline phosphatase (ALP) atscreening. A participant with mildly elevated ALT or AST up to < 2 × upper limit ofnormal (ULN) can be enrolled if TBL and DBL are normal. Participant with mildlyelevated ALP (up to < 1.5 × ULN) can be enrolled if cholestatic liver disease isexcluded and no cause other than fatty liver is diagnosed. Participant withGilbert's syndrome with elevated TBL may be enrolled as long as DBL, hemoglobin andreticulocytes are normal.

• Participant has creatinine > 1.5 x ULN; or estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease formula < 30 mL/min/1.73 m2at the screening visit.

• Participant has a history of endometrial hyperplasia or uterine/endometrial cancer.

• Participant has a medical condition or chronic disease (including history ofneurological [including cognitive], hepatic, renal, cardiovascular,gastrointestinal, pulmonary [e.g., moderate asthma], endocrine, or gynecologicaldisease) or malignancy that could confound interpretation of the study outcome.

• Participant uses a prohibited therapy (menopause hormone therapy (MHT),estradiol-containing hormonal contraceptive progestin and progesterone-onlymedicines, any treatment for VMS [prescription medications, over-the-counter, orherbal] or CYP1A2 (cytochrome P450) inhibitors) or is not willing to wash out suchdrugs; in addition, medications that are contraindicated due to underlying breastcancer diagnosis and the adjuvant endocrine therapy.

• Participant has a known substance abuse or alcohol addiction within 6 months ofscreening.

• Participant has received any investigational therapy within 90 days or 5 half-lives,whichever is longer, prior to screening.

• Participant has any condition, which makes the participant unsuitable for studyparticipation.

• Participant has a known or suspected hypersensitivity to fezolinetant, the adjuvantendocrine therapy being used, or any components of the formulations used.