FLASH-Breast: Evaluating the Efficacy of Fezolinetant in Reducing Vasomotor Symptoms in Women With Breast Cancer on Endocrine Therapy

Inclusion criteria

• Women with diagnosed, histologically confirmed, clinical stage I-III, HR+ invasive breast cancer as defined by ASCO CAP guidelines for whom adjuvant endocrine therapy would be indicated, regardless of HER2 status.
• Age 18 years and older.
• Currently on endocrine therapy (tamoxifen or aromatase inhibitors) as part of standard of care treatment for HR+ breast cancer. Endocrine therapy may be administered with or without ovarian suppression and/or CDK4/6 inhibitors as permitted in Section 7.1.1. Participants with HER2-positive disease are eligible and may receive concurrent HER2 monoclonal antibody therapy (e.g., trastuzumab or pertuzumab), but not HER2 antibody-drug conjugates (e.g., ado-trastuzumab emtansine T-DM1, or trastuzumab deruxtecan T-DXd).
• Willing and able to provide written informed consent/assent for the trial.
• Postmenopausal as defined by spontaneous amenorrhea for at least 12 consecutive months, spontaneous amenorrhea for at least 6 months with biochemical criteria or menopause (FSH \> 40 IU/L), or bilateral oophorectomy for at least 6 weeks before the screening visit, or if premenopausal chemically suppressed by GnRH agonist therapy with ultrasensitive estradiol level \<10.
• n endocrine therapy for a minimum of 3 months and has planned duration of 12 weeks left in the treatment regimen. Participants receiving a CDK4/6 inhibitor must have been on treatment for at least 4 weeks prior to enrollment.
• Experiencing an average of seven or more moderate to severe hot flashes per day over a 7-day period as documented by Symptom Diary during the Screening Period and seeking treatment or relief for VMS.
• Able to swallow oral formulation of the study agent.

Exclusion criteria

• Participants who have a diagnosis of stage IV metastatic disease.
• Receiving any other cancer treatment other than endocrine therapy. This includes chemotherapy, targeted therapies, and immunotherapy.
• Receiving cytochrome CYP1A2 inhibitors.
• Participants who have initiated, discontinued, or had a dose adjustment of treatment for vasomotor symptoms (prescription, over the counter, or herbal) within 28 days prior to screening.
• Pregnant or lactating patients.
• Known cirrhosis or active liver disease, jaundice, or elevated liver aminotransferases (ALT or AST) \>2x ULN, or elevated total bilirubin, OR elevated direct bilirubin, or elevated INR, or elevated alkaline phosphatase \>2x ULN.
• Creatinine \> 1.5 times upper limit of normal; or estimated GFR ≤ 30 mL/min per 1.73 m2 at screening.
• Judgement by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements.