Efficacy and Safety of Elinzanetant in Treating Vasomotor Symptoms Induced by Adjuvant Endocrine Therapy in Hormone-Receptor Positive Breast Cancer Patients

The primary objective of this study is to evaluate the **efficacy** of elinzanetant for the treatment of **vasomotor symptoms** (VMS) caused by adjuvant endocrine therapy in women with, or at high risk for developing hormone receptor positive breast cancer. This is clinically relevant as VMS significantly impacts the quality of life in this patient population, and effective management is crucial for adherence to cancer therapy.

Secondary objectives include:

• Evaluating the onset of efficacy of elinzanetant for the treatment of VMS caused by adjuvant endocrine therapy in the specified patient group.
• Assessing the efficacy of elinzanetant on sleep quality and menopause-related quality of life in women with, or at high risk for developing hormone receptor positive breast cancer.
• Evaluating the safety of elinzanetant for the treatment of VMS in the same patient population.

The clinical trial involves a total of **57 participants**, specifically targeting **females** aged 18 to 70 years. The study population comprises women experiencing **vasomotor symptoms** due to adjuvant endocrine therapy, either currently diagnosed with hormone-receptor positive breast cancer or at high risk for developing it. Participants are required to have completed a Hot Flash Daily Diary for at least 11 days in the two weeks prior to the baseline visit, documenting a minimum of 35 moderate to severe hot flashes. The trial exclusively includes female subjects, with no male participants involved. The selection process ensures that participants are expected to continue their current endocrine therapy, which may include Tamoxifen or Aromatase inhibitors, with or without gonadotropin-releasing hormone analogues, throughout the study duration. The trial population is considered vulnerable, and contraceptive use is mandated in accordance with local regulations, except for post-menopausal women or those of non-childbearing potential. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** study to evaluate the efficacy and safety of **elinzanetant** for the treatment of **vasomotor symptoms** caused by adjuvant endocrine therapy in women with, or at high risk for developing, hormone-receptor positive breast cancer. The trial will span a total duration of 52 weeks, with an optional extension for an additional two years. Participants will be randomly assigned to receive either the active treatment, elinzanetant, or a placebo, both administered in the form of soft capsules taken orally. The primary objective is to assess the mean change in frequency of moderate to severe hot flashes from baseline to Week 4 and Week 12, as recorded in the Hot Flash Daily Diary (HFDD).

The study will commence with an inclusion visit, where eligibility criteria will be confirmed. Participants must be females aged 18 to 70 years, experiencing vasomotor symptoms due to adjuvant endocrine therapy, and have a personal history or high risk of developing hormone-receptor positive breast cancer. They must also have completed the HFDD for at least 11 days in the two weeks preceding the baseline visit, recording at least 35 moderate to severe hot flashes. Follow-up visits will occur at regular intervals to monitor the frequency and severity of symptoms, as well as to assess secondary endpoints such as changes in sleep disturbance and quality of life scores. The end-of-study visit will conclude the trial, evaluating the overall efficacy and safety of the treatment.

Participant involvement is expected to last for the entire 52-week period, with the possibility of extending participation for an additional two years if they opt into the extension phase. Conditions that may lead to early termination from the study include non-compliance with the study protocol, adverse events, or withdrawal of consent. The trial is structured to ensure rigorous data collection and analysis, maintaining the integrity and reliability of the results.

The clinical trial involves the administration of **elinzanetant**, an experimental medication, for the treatment of vasomotor symptoms caused by adjuvant endocrine therapy in women with, or at high risk for developing hormone-receptor positive breast cancer. The investigational product, identified as BAY 3427080, is formulated as a **capsule, soft** and is administered orally. The maximum daily dose of elinzanetant is 120 mg, with a total maximum dose of 131,400 mg over a treatment period of up to 36 months. The active substance, elinzanetant, is of chemical origin and is manufactured by Bayer AG. The dosing schedule is designed to ensure optimal efficacy and safety, with participant compliance monitored throughout the study duration.

In addition to the experimental treatment, a placebo comparator is utilized in this double-blind, randomized, placebo-controlled study. The placebo is presented as BAY 3427080 60 mg capsules, matching the appearance of the active treatment to maintain blinding. The placebo does not contain any active substance and serves as a control to evaluate the efficacy of elinzanetant. The administration of the placebo follows the same oral route and dosing schedule as the active treatment, ensuring consistency in the study protocol.

The efficacy of **elinzanetant** in the treatment of vasomotor symptoms (VMS) caused by adjuvant endocrine therapy in women with, or at high risk for developing hormone-receptor positive breast cancer, will be assessed through a double-blind, randomized, placebo-controlled multicenter study. The primary endpoints for evaluating efficacy include the mean change in frequency of moderate to severe hot flashes (HF) from baseline to Week 4 and Week 12, as assessed by the Hot Flash Daily Diary (HFDD). Secondary endpoints will further evaluate the mean change in severity of moderate to severe HF from baseline to Week 4 and Week 12, as well as the mean change in frequency of moderate to severe HF from baseline to Week 1 and over time. Additional secondary endpoints include the mean change in patient-reported outcomes measurement information system sleep disturbance short form 8b (PROMIS SD SF 8b) total score and the menopause-specific quality of life scale (MENQOL) total score from baseline to Week 12.

The HFDD will be utilized as a validated tool for collecting data on the frequency and severity of hot flashes, with assessments scheduled at specified timepoints throughout the study. The analysis of these efficacy parameters will be conducted to determine the therapeutic impact of elinzanetant compared to placebo, providing insights into its potential benefits for the target population. The study is designed to ensure rigorous evaluation of the treatment's efficacy over a 52-week period, with an optional extension for an additional two years.