This phase II trial studies how well imlunestrant and abemaciclib work in treating patients with estrogen receptor positive (ER+) breast cancer who have tumor remaining in the blood following treatment (minimal residual disease). Estrogen can cause the growth of breast cancer cells. Imlunestrant lowers the amount of estrogen made by the body. This may help stop the growth of tumor cells that need estrogen to grow. Abemaciclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Imlunestrant and abemaciclib may be effective in treating patients with ER+ breast cancer who have minimal residual disease.
Eligibility criteria
This trial does not accept healthy volunteers
Qualifiers
Participants must have localized ER+ (≥ 10% on surgical pathology), HER2 negative, any grade, invasive breast cancer. Pathological stage (from time of surgery, including patients who received neoadjuvant therapy) I - III by American Joint Committee on Cancer (AJCC) 8th edition staging
Note: Invasive breast cancer must be ER+ in ≥ 10% of the cells and HER2 negative (immunohistochemistry [IHC] 0 or 1+ and/or fluorescence in situ hybridization [FISH] negative with a ratio < 2) by American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines. For Immunohistochemistry (IHC) 2+, the tumor must be FISH negative with a ratio < 2. ER, progesterone receptor (PR) and HER2 measurements should be performed according to institutional (local) guidelines, in a Clinical Laboratory Improvement Act (CLIA)-approved setting
Detectable ctDNA in a CLIA-certified lab (separate pre-screening consent available) within the past six months. Participants must have no clinical or radiographic evidence of recurrence as determined by the treating investigator
Confirmation of adequate archival tissue (either initial biopsy or surgical specimen) (15-20 unstained slides cut at 5 µm or 1 block) required before study entry. If adequate surgical tissue is available, this is preferred. Otherwise tissue from diagnostic biopsy is acceptable. If adequate tissue not available, principal investigator (PI) approval is required prior to study entry
Disqualifiers
Participants with metastatic disease (including contralateral axillary lymph nodes) or inflammatory breast cancer. Of note, if a patient had locally advanced breast cancer leading to inflammation, this would not exclude the patient on the grounds of inflammatory carcinoma
Participants who have had CDK 4/6 inhibitor therapy within the past 6 months. Use of prior CDK 4/6 inhibitor with last dose more than 6 months ago is permitted
Participants who are receiving any other anti-cancer investigational agents. Participation in other observational studies is permitted
History of other malignancies within past 5 years, except ductal carcinoma in situ of the breast, cervical cancer in situ, melanoma in situ, and basal cell or squamous cell carcinoma of the skin. No concurrent malignancy or other serious medical condition as deemed by the investigator
Trial design
Design model
Single group
Treatments tested in this trial
Abemaciclib
Drug
Given PO
Biospecimen Collection
Procedure/Surgery
Undergo blood sample collection
Imlunestrant
Drug
Given PO
Questionnaire Administration
Other intervention
Ancillary studies
Radiologic Imaging Procedure
Procedure/Surgery
Undergo radiologic scans
Treatment groups
42 Participants
are divided into 1 treatment group
Group A: Treatment (abemaciclib, imlunestrant)Experimental treatment 5 interventions
Trial outcomes
Primary outcomes
1
Rate of circulating tumor deoxyribonucleic acid (ctDNA) clearance
Clearance of ctDNA is defined as having undetectable plasma ctDNA after completion of 12 cycles of adjuvant imlunestrant and abemaciclib. The rate of ctDNA clearance will be calculated as the percentage of all enrolled patients that have undetectable plasma after completion of adjuvant imlunestrant and abemaciclib (12 cycles or sooner if trial therapy is discontinued), and its Wilson 95% confidence interval will be reported.
Time frame
After 12 cycles (Cycle length = 28 days)
Secondary outcomes
1
Rate of ctDNA re-emergence
Of participants with ctDNA clearance, rate of re-emergence of ctDNA (development of detectable ctDNA after previous ctDNA clearance) in the 12 cycles following treatment will be calculated. The time from discontinuation of protocol therapy to ctDNA re-emergence will be estimated using the Kaplan-Meier method.
Time frame
Up to 1 year after treatment
2
Distant recurrence-free survival
Will be estimated based on Kaplan-Meier method. Events will be defined as having clinical or radiographic evidence of distant metastatic recurrence or death due to any cause. Participants alive without distant disease recurrence will be censored at date of last evaluation. The distant recurrence will be determined by the treating investigator based on routine clinical evaluation and/or imaging, as part of standard follow-up. If recurrence is suspected, it will be confirmed by pathological confirmation to document carcinoma, as per as per National Comprehensive Cancer Network guidelines.
Time frame
From enrollment to evidence of distant disease recurrence or death due to any cause, assessed up to 1 year
3
Incidence of adverse events
Safety and tolerability will be determined by the investigator based on Common Terminology Criteria for Adverse Events version 5. The frequency and severity of adverse events will be summarized, and the proportion of patients who discontinue the treatment due to toxicity (and a Wilson 95% confidence interval) will be calculated.
Time frame
Up to 30 days after the last dose of study treatment
Other outcomes
Sponsors and contacts
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