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

Official title

preEMBER: A Phase 2, Open-label Study Evaluating Imlunestrant in Premenopausal Women With Estrogen Receptor-Positive, HER2-Negative Breast Cancer

Overview

This study will include two groups of patients: Cohort 1 and Cohort 2. Cohort 1: will help researchers learn how a medicine called imlunestrant (LY3484356) affects a specific type of breast cancer. Some patients will take both imlunestrant and another treatment to suppress their ovarian function. Some will take it without ovarian suppression. Researchers will compare the effects in breast cancer cells to those of another medicine called tamoxifen. All patients in this group will be premenopausal women who have a type of early breast cancer called estrogen receptor-positive, HER2-negative. The treatment in this group will last for up to 29 days. Cohort 2: will help researchers understand how imlunestrant affects the ovaries when it is taken without ovarian suppression. Researchers will compare the effects to those of another medicine called tamoxifen. This group will also include premenopausal women with the same type of breast cancer. The treatment in this group will last for up to 6 months.

Interventions

• Drug Imlunestrant
  Given orally
• Drug Goserelin
  Given SC
• Drug Tamoxifen 20 mg
  Given orally

Primary outcome measures

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

Secondary outcome measures (3)

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

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 32 centers

• University of Alabama at Birmingham — Birmingham
• Ironwood Cancer & Research Centers — Chandler
• Mayo Clinic in Arizona - Phoenix — Phoenix
• USC/Norris Comprehensive Cancer Center — Los Angeles
• UCLA Hematology/Oncology - Parkside — Santa Monica
• Banner MD Anderson Cancer Center at North Colorado Medical Center — Greeley
• Banner MD Anderson Cancer Center at McKee Medical Center — Loveland
• AdventHealth Altamonte Springs — Altamonte Springs
• … and 24 more centers

Germany · 31 centers

• Evangelisches Krankenhaus Bergisch Gladbach — Bergisch Gladbach
• Praxis am Volkspark — Berlin
• Onkologische Schwerpunktpraxis Bielefeld — Bielefeld
• Augusta-Kranken-Anstalt — Bochum
• Gynaekologisches Zentrum Bonn — Bonn
• Marienhospital Bottrop — Bottrop
• Onkologisch - Hämatologische Schwerpunktpraxis — Bremen
• Krankenhaus Köln-Holweide — Cologne
• … and 23 more centers

Italy · 6 centers

• Ente Ospedaliero Ospedali Galliera — Genova
• Humanitas — Milan
• Istituto Europeo di Oncologia IRCCS — Milan
• Humanitas Istituto Clinico Catanese — Misterbianco
• Nuovo Ospedale di Prato-S.Stefano — Prato
• Fondazione Policlinico Universitario Agostino Gemelli — Roma

Taiwan · 6 centers

Center list to be confirmed — check the primary protocol.

France · 5 centers

• CHRU de Brest — Brest
• Centre de Cancérologie du Grand Montpellier — Montpellier
• Hôpital Privé Des Côtes d'Armor — Plérin
• Institut Curie - site Saint-Cloud — Saint-Cloud
• Gustave Roussy — Villejuif

Belgium · 3 centers

• Cliniques universitaires Saint-Luc — Brussels
• Antwerp University Hospital — Edegem
• UZ Leuven — Leuven

Ireland · 3 centers

• St. Vincent's University Hospital — Dublin
• St. James's Hospital — Dublin
• Galway University Hospital — Galway

Identifiers

NCT: NCT07287098 · 27511 · 2025-523258-15-00 · J2J-MC-JZLL

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗