Brief Summary:
The main purpose of this study is to measure how well imlunestrant works compared to standard
hormone therapy in participants with early breast cancer that is estrogen receptor positive
(ER+) and human epidermal receptor 2 negative (HER2-). Participants must have already taken
endocrine therapy for two to five years and must have a higher-than-average risk for their
cancer to return. Study participation could last up to 10 years.
Inclusion Criteria:
- Have a diagnosis of ER+, HER2- early-stage, resected, invasive breast cancer without
evidence of distant metastasis.
- Participants must have received at least 24 months but not more than 60 months of any
adjuvant ET, from time of adjuvant ET initiation.
- Participants may have received (neo) adjuvant chemotherapy and/or targeted therapy
with a CDK4/6- or PARP- inhibitor.
- Must have an increased risk of disease recurrence based on clinical-pathological risk
features.
- Have a Performance Status of 0 or 1 on the Eastern Cooperative Oncology Group scale.
- Have adequate organ function.
Exclusion Criteria:
- Have any evidence of metastatic disease (including contralateral ALN) or inflammatory
breast cancer at primary breast cancer diagnosis.
- Participants with more than a 6-month consecutive gap in therapy during the course of
prior adjuvant ET.
- Participants who have completed or discontinued prior adjuvant ET >6 months prior to
screening.
- Participants with a history of previous breast cancer are excluded, with the exception
of ipsilateral DCIS treated by locoregional therapy alone ≥5 years ago.
- Pregnant, breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with the screening visit through 180 days
after the last dose of study intervention.
- Participant has previously received ET of any duration for breast cancer prevention
(tamoxifen or AIs) or raloxifene.
- Participants with a history of any other cancer.
- Have serious preexisting medical conditions that, in the judgment of the investigator,
would preclude participation in this study.
Primary outcome:
1. Invasive Disease-Free Survival (IDFS) (Time Frame - Randomization to recurrence or death from any cause (up to 10 years)):
IDFS excluding second non-breast primary invasive cancers
Secondary outcome:
1. Distant Recurrence-Free Survival (DRFS) (Time Frame - Randomization to Distant Recurrence or Death from Any Cause (up to 10 Years)):
DRFS
2. Overall Survival (OS) (Time Frame - Randomization to Death from Any Cause (up to 10 Years)):
OS
3. Pharmacokinetics (PK): Steady State Plasma Concentrations of Imlunestrant (Time Frame - Year 1, Month 2 to Month 4):
PK: steady state plasma concentrations of imlunestrant
4. Change from Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (EORTC QLQ-C30) Physical Functioning (Time Frame - Visit 1 Day 1 up to end of Year 5):
The EORTC QLQ-C30 is a 30-question patient reported instrument used to assess multidimensional quality of life (QOL) in cancer patients. It consists of 15 domains: 1 global QOL scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). Physical functioning was measured by items 1 to 5. The sum score was linearly transformed to the range 0 - 100 as recommended by the EORTC (higher score is better).
5. Change from Baseline in the EORTC QLQ-C30 Role Functioning (Time Frame - Visit 1 Day 1 up to end of Year 5):
The EORTC QLQ-C30 is a 30-question patient reported instrument used to assess the multidimensional QOL in cancer patients. It consists of 15 domains: 1 global QOL scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). Role functioning was measured by items 6 and 7. The sum score was linearly transformed to the range 0 - 100 as recommended by the EORTC (higher score is better).
6. Change from Baseline in the EORTC QLQ-C30 Global QOL (Time Frame - Visit 1 Day 1 up to end of Year 5):
The EORTC QLQ-C30 is a 30-question patient reported instrument used to assess the multidimensional QOL in cancer patients. It consists of 15 domains: 1 global QOL scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). Global QOL was measured by items 29 and 30. The sum score was linearly transformed to the range 0 - 100 as recommended by the EORTC (higher score is better).
7. Proportion of Time on Study Treatment with High Overall Adverse Event Burden (Time Frame - Visit 1 Day 1 up to end of Year 5):
FACT GP5 = Functional Assessment of Cancer Therapy - General Physical Well-being Item 5 (FACT GP5). High overall adverse event burden is defined as a score of 3 or 4 on a 5-point Likert scale. Higher scores represent higher symptom burden.
- Experimental: Imlunestrant
Imlunestrant administered orally. - Active Comparator: Investigator's Choice of Endocrine Therapy
Investigator's choice of tamoxifen, anastrozole, letrozole, or exemestane administered per local approved label.
- Imlunestrant (LY3484356):
Administered orally. - Tamoxifen:
Administered per local approved label. - Anastrozole:
Administered per local approved label. - Letrozole:
Administered per local approved label. - Exemestane:
Administered per local approved label.
Quelle: ClinicalTrials.gov
