Phase 2 Open‑Label Study of LY3484356 (imlunestrant) versus Tamoxifen or LY3484356 + Goserelin in Premenopausal ER‑Positive HER2‑Negative Early Breast Cancer

Primary objectives are to assess the effect of imlunestrant versus tamoxifen on tumor cell proliferation, to compare imlunestrant with imlunestrant + goserelin regarding the same pharmacodynamic endpoint, and to evaluate the incidence of symptomatic ovarian cysts with imlunestrant versus tamoxifen. These endpoints address pharmacodynamic activity and safety in premenopausal women with estrogen receptor‑positive, HER2‑negative early breast cancer.

The study enrolled 239 premenopausal female patients with early‑stage invasive breast cancer; all participants were classified as vulnerable due to their reproductive status. Eligibility required histologically confirmed Stage I‑III Estrogen Receptor positive, human epidermal growth factor receptor 2‑negative (HER2‑) disease with a Ki‑67 index of at least 10 %, an Eastern Cooperative Oncology Group performance status of 0 or 1, adequate organ function, and the ability to swallow oral capsules or tablets. Additional criteria included prior definitive locoregional therapy, receipt of at least 4.5 years of adjuvant endocrine therapy (or at least 2 years without planned ovarian suppression), and the use of a highly effective non‑hormonal contraceptive method for those of childbearing potential. Participants were selected on the basis of these clinical and pathological features; no specific dietary, physical activity, or other lifestyle restrictions were stipulated in the protocol.

The study is a Phase 2, open‑label trial evaluating the oral selective estrogen receptor degrader imlunestrant (400 mg tablet) compared with tamoxifen (20 mg tablet) and with the combination of imlunestrant plus subcutaneous goserelin acetate (3.6 mg). Eligible participants are premenopausal women with histologically confirmed Estrogen Receptor‑Positive, HER2‑negative early‑stage invasive breast cancer (Stage I‑III) and a Ki‑67 index ≥10 %. The research methodology comprises parallel treatment arms with allocation based on predefined criteria; the trial is not blinded. The overall study period extends from the planned recruitment start on 30 June 2026 to an estimated completion date of 15 June 2029. Study procedures begin with a screening visit to verify inclusion and exclusion criteria, followed by a baseline visit during which the initial dose is administered and pre‑treatment tumor samples are obtained. Participants then attend scheduled on‑treatment visits for safety assessments, tumor‑biopsy collection, and monitoring of ovarian cysts, continuing until the planned end‑of‑study visit, which occurs after the final treatment cycle and includes a post‑treatment tumor evaluation. Total participant involvement spans the entire treatment and follow‑up period, typically several months. Early termination may occur if a participant experiences a grade 3 or higher adverse event related to study medication, demonstrates disease progression, withdraws consent, or fails to comply with protocol‑required assessments.

The experimental agent, LY3484356, is supplied as an oral tablet containing 400 mg of the active substance. It is administered by mouth once daily throughout the treatment period. Dose adjustments are not permitted, and compliance is monitored by tablet count and patient diary entries at each study visit.

The comparator arm includes tamoxifen citrate, provided as an oral tablet delivering 20 mg of the active ingredient. The medication is taken by mouth once daily in accordance with standard breast‑cancer therapy guidelines. Adherence is assessed through pill count and patient self‑report.

The second comparator component is goserelin acetate, a subcutaneous formulation containing 3.6 mg of the active compound. It is injected subcutaneously according to the approved schedule for ovarian suppression, typically every 28 days, with administration documented by study staff. Injection site assessments are performed at each dosing visit to ensure proper administration.

All study medications are dispensed in blinded packaging, and dosing schedules are recorded in the case report form. Participants receive counseling on proper administration techniques, and compliance is reinforced through scheduled reminders and verification of returned medication at each clinic visit.

Efficacy will be evaluated using two primary endpoints. The first endpoint is the change from baseline in Ki-67 expression, which serves as a marker of tumor cell proliferation. The second endpoint is the rate of symptomatic ovarian cysts observed during the study.