A Study of Imlunestrant (LY3484356) in Premenopausal Women With Estrogen Receptor-Positive (ER+) Human Epidermal Growth Factor Receptor 2 Negative (HER2-) Early Breast Cancer

• Imlunestrant (Drug), also known as LY3484356: Given orally
• Goserelin (Drug): Given SC
• Tamoxifen 20 mg (Drug): Given orally

Primary outcomes

• Change from Baseline in Antigen Kiel (Ki-67) Expression [Baseline, Day 29]
• Rate of Symptomatic Ovarian Cysts [Up to Day 180]

Secondary outcomes

• Change from Baseline in Estrogen Receptor (ER) Expression [Baseline, Day 29]
• Change from Baseline in Progesterone Receptor (PR) Expression [Baseline, Day 29]
• Rate of Complex Ovarian Cysts [Up to Day 180]

Sex: Female, ages: 18 Years to any

Inclusion Criteria:

Cohort 1:

* Have histologically confirmed Stage I to III Estrogen Receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) invasive breast carcinoma with Ki-67 at least 10%
* Be willing and able to provide pre- and on-treatment tumor samples.
* Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Be able to swallow capsules or tablets.
* Be premenopausal women.
* If of childbearing potential must use 1 highly effective method of non-hormonal contraception while receiving study treatment and for the duration specified in protocol.
* Have adequate organ function.

Cohort 2:

* Have a diagnosis of ER+, HER2- early-stage, resected, invasive breast cancer without evidence of distant metastasis
* Have undergone definitive loco-regional therapy.
* Have received at least 4.5 years of any adjuvant endocrine therapy (ET), or at least 2 years of adjuvant ET with no additional ovarian suppression planned.
* Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Be able to swallow capsules or tablets.
* Be premenopausal women
* If of childbearing potential must use 1 highly effective method of non-hormonal contraception while receiving study treatment and for the duration specified in protocol.
* Have adequate organ function.

Exclusion Criteria:

Cohort 1:

* Have bilateral invasive metastatic, occult primary, or inflammatory breast cancer.
* Have had prior bilateral oophorectomy or ovarian ablation.
* Have a serious medical condition
* Had major surgery within 28 days prior to randomization.
* Have a history of other cancer (except non melanoma skin cancer, Stage I uterine cancer, or carcinoma in situ of the cervix or other in situ cancer), unless in complete remission with no therapy for a minimum of 1 year.
* Plan to receive concurrent neoadjuvant therapy with any other non-protocol anticancer therapy.
* Have had any prior therapy for an invasive or non-invasive breast cancer.
* Have had prior radiotherapy to the ipsilateral chest wall for any malignancy.
* Have received prior anti-estrogen therapy, including for osteoporosis or prevention of breast cancer.
* Have had prior treatment with any Gonadotropin-releasing hormone (GnRH) agonist within 12 months prior to randomization.
* Receiving current exogenous reproductive hormone therapy

Cohort 2:

* Have ovarian cyst(s) greater than (>) 1 centimeter (cm) at screening.
* Have metastatic occult primary, or inflammatory breast cancer.
* Have had prior bilateral oophorectomy or ovarian ablation.
* Have a serious medical condition
* Had major surgery within 28 days prior to randomization.
* Have a history of other cancer (except non melanoma skin cancer or carcinoma in situ of the cervix or other in situ cancer), unless in complete remission with no therapy for a minimum of 1 year.
* Completed or discontinued prior adjuvant ET >6 months prior to screening.
* Have received prior therapy with any selective estrogen receptor degrader (SERD).
* Receiving current exogenous reproductive hormone therapy.

• Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST), Study director, Eli Lilly and Company

NIH grants: 2025