Neoadjuvant Imlunestrant Plus Abemaciclib Treatment Guided by Ki67 Index After 2 Weeks for ER-Positive HER2-Negative Breast Cancer

Neoadjuvant Imlunestrant Plus Abemaciclib Treatment Guided by Ki67 Index After 2 Weeks for ER-Positive HER2-Negative Breast Cancer: A Randomized Phase 2 Trial (IMPATIENS)

This is a prospective, open-label, single-center, randomized controlled Phase II clinical study aimed at evaluating the efficacy and safety of neoadjuvant imlunestrant combined with abemaciclib guided by the Ki67 index after 2 weeks in patients with ER+/HER2- breast cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Imlunestrant + abemaciclib; Drug: (dd)EC*4-T*4

Detailed Description

This is a prospective, open-label, single-center, randomized controlled Phase II clinical study aimed at evaluating the efficacy and safety of neoadjuvant imlunestrant combined with abemaciclib guided by the Ki67 index after 2 weeks in patients with ER+/HER2- breast cancer. Eligible subjects who provide informed consent will first receive a 2-week window-of-opportunity treatment with imlunestrant combined with abemaciclib, followed by a biopsy of the primary lesion to assess Ki67 at 2 weeks. If the Ki67 of the primary lesion after 2 weeks is <7.4%, they will be randomized in a 1:1 ratio to either Imlunestrant plus abemaciclib or neoadjuvant chemotherapy. If the Ki67 of the primary lesion after 2 weeks is ≥7.4%, patients will be assigned to neoadjuvant chemotherapy.

• Study Type: Interventional
• Enrollment (Estimated): 189
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Fudan University Shanghai Cancer Center
      • Contact: Keda Yu, Professor; Phone Number: +86-021-64175590; Email: yukeda@fudan.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Female patients aged 18 to 75 years.
2. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
3. Primary breast tumor diameter > 1 cm.
4. Histologically confirmed invasive ER+/HER2- breast cancer, meeting ER≥50% and Ki67≥10%. HER2 negativity is defined as HER2 immunohistochemistry (IHC) 0-1+, or IHC 2+ with fluorescence in situ hybridization (FISH) confirming no amplification.
5. Clinical tumor stage: cT1c-T4, cN0-cN2, cM0.
6. Willing to undergo breast cancer surgery once surgical criteria are met after neoadjuvant therapy.

7. Adequate organ function, meeting all of the following:

   • Hemoglobin (Hb)≥90 g/L and patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin earlier than the day after the erythrocyte transfusion;
   • Absolute neutrophil count (ANC)≥1.5×10^9/L;
   • Platelet count (PLT)≥100×10^9/L;
   • Total bilirubin (TBIL)≤1.5×the upper limit of normal (ULN) and patients with Gilbert's syndrome with a total bilirubin ≤2.0 times ULN and direct bilirubin within normal limits are permitted;
   • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)≤2.5×ULN;
   • Alkaline phosphatase (ALP)≤2.5×ULN;
   • Serum creatinine (Cr)≤1.5×ULN;
   • Prothrombin time (PT) and activated partial thromboplastin time (APTT)≤1.5×ULN, and international normalized ratio (INR)≤1.5×ULN (in patients not receiving anticoagulation).
8. Left ventricular ejection fraction (LVEF)≥55% at baseline as measured by echocardiography or multi-gated acquisition (MUGA) scan.

9. Women with premenopausal status should receive ovarian suppression with a gonadotropin-releasing hormone agonist such as goserelin or leuprolide before initiation of treatment to become postmenopausal status. Postmenopausal due to surgical/natural menopause requires at least 1 of the following:

   • prior bilateral oophorectomy;
   • age≥60 years;
   • age<60 years, amenorrheic for at least 12 months (in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression), and FSH and estradiol levels in the postmenopausal range.
10. Women of childbearing potential must have a negative serum pregnancy test. Such patients must use a medically acceptable method of contraception during study treatment and for at least 6 months after the last dose of the study drug(s).
11. The subject voluntarily agrees to participate, signs the informed consent form, has good compliance, and is willing to adhere to follow-up.

Exclusion Criteria:

1. Stage IV (metastatic) breast cancer or bilateral breast cancer.
2. Prior history of invasive breast cancer.
3. Prior history of ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS).
4. Any prior chemotherapy, endocrine therapy, or anti-HER2 therapy for breast cancer; or prior excisional biopsy of the primary breast tumor and/or axillary lymph nodes, or prior local radiotherapy (excluding diagnostic biopsy for primary breast cancer or surgery for benign breast tumors).
5. Any other malignancy within the past 5 years, except cured cervical carcinoma in situ and non-melanoma skin cancer.
6. Peripheral neuropathy≥Grade 2 per NCI-CTCAE v6.0.
7. Serious cardiovascular or cerebrovascular disease within 6 months prior to randomization, including but not limited to congestive heart failure, unstable angina, severe arrhythmias uncontrolled by medication, severe conduction abnormalities or clinically significant valvular disease, uncontrolled severe hypertension, myocardial infarction, or cerebrovascular accident.
8. Any serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment [e.g. estimated creatinine clearance <30ml/min], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea).
9. Major surgery within 4 weeks prior to randomization without full recovery, or an anticipated need for major surgery during study treatment.
10. Known active liver disease, including but not limited to active hepatitis B (defined as HBsAg positive with HBV-DNA≥1000 IU/mL), hepatitis C (defined as HCV-Ab positive with HCV-RNA above the assay's lower limit of quantification), or autoimmune liver disease.
11. Severe and uncontrolled infection or known HIV infection.
12. Active systemic bacterial infection (requiring intravenous antibiotics at time of initiating study treatment) or fungal infection.
13. Pregnant or breastfeeding.
14. Known allergy to the study drug or any of its excipients, or a history of severe hypersensitivity reactions to other monoclonal antibodies.
15. Known abuse of psychotropic substances, alcoholism, or drug abuse.
16. Known, definite neurological or psychiatric disorders associated with poor compliance, including but not limited to epilepsy or dementia.
17. Any other serious physical or mental illness or laboratory abnormality that may increase the risk of study participation or interfere with study treatment and outcomes, or any other condition that, in the investigator's judgment, makes the patient unsuitable for this study.
18. The patient has received an experimental treatment in a clinical trial within the last 30 days or 5 half-lives, whichever is longer, prior to randomization, or is currently enrolled in any other type of medical research (for example: medical device) judged by the sponsor not to be scientifically or medically compatible with this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A (Imlunestrant + abemaciclib); If the Ki67 of the primary lesion after 2 weeks is <7.4%	Drug: Imlunestrant + abemaciclib; Imlunestrant (400 mg orally, once daily) combined with abemaciclib (150 mg orally, twice daily) for 24 weeks.
Active Comparator: Arm B [(dd)EC*4-T*4]; If the Ki67 of the primary lesion after 2 weeks is <7.4%	Drug: (dd)EC*4-T*4; Epirubicin (90 mg/m², intravenous infusion) combined with cyclophosphamide (600 mg/m², intravenous infusion, every 2 weeks or 3 weeks, determined by investigators) for 4 cycles, followed by docetaxel (100 mg/m², intravenous infusion, every 3 weeks) for 4 cycles.
Active Comparator: Arm C [(dd)EC*4-T*4]; If the Ki67 of the primary lesion after 2 weeks is ≥7.4%	Drug: (dd)EC*4-T*4; Epirubicin (90 mg/m², intravenous infusion) combined with cyclophosphamide (600 mg/m², intravenous infusion, every 2 weeks or 3 weeks, determined by investigators) for 4 cycles, followed by docetaxel (100 mg/m², intravenous infusion, every 3 weeks) for 4 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR between Arm A and Arm B	Defined as the proportion of patients whose tumor shrinks by a certain amount and maintains that reduction for a certain time, including cases of complete response (CR) and partial response (PR). Tumor objective response will be assessed using the Response Evaluation Criteria in Solid Tumors (RECIST version 1.1). Subjects must have measurable tumor lesions at baseline.	Immediately after the surgery
pCR rate between Arm A and Arm B	Defined as achieving pCR (ypT0/is, ypN0) upon postoperative pathological assessment, meaning the absence of any residual invasive cancer in the pathological evaluation of hematoxylin and eosin-stained resected breast samples and all ipsilateral lymph node samples after completing neoadjuvant therapy and surgery.	Immediately after the surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative changes of Ki67 index between Arm A and Arm B	Defined as the geometric mean percentage change in Ki67 index from baseline to post-surgery. For patients with no detectable invasive cancer in the primary site post-surgery, a Ki67 value of 0.01 will be used as a substitute.	Immediately after the surgery
3-year EFS between Arm A and Arm B	Defined as the time from randomization to the first recorded relevant event. Relevant events include preoperative disease progression, postoperative disease recurrence or metastasis, contralateral invasive breast cancer, second primary invasive cancer, and death from any cause.	Following surgery until Year 3
3-year OS between Arm A and Arm B	Defined as the time from randomization to death from any cause. For subjects still alive at the last follow-up, OS is censored at the last follow-up time.	Following surgery until Year 3
Adverse events assessed according to CTCAE v6.0 criteria	To evaluate the rate of adverse effects of patient by the standard CTCAE scale (V6.0)	Up to one year during follow-up

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR between Arm A and Arm C	Defined as the proportion of patients whose tumor shrinks by a certain amount and maintains that reduction for a certain time, including cases of complete response (CR) and partial response (PR). Tumor objective response will be assessed using the Response Evaluation Criteria in Solid Tumors (RECIST version 1.1). Subjects must have measurable tumor lesions at baseline.	Immediately after the surgery
pCR rate between Arm A and Arm C	Defined as achieving pCR (ypT0/is, ypN0) upon postoperative pathological assessment, meaning the absence of any residual invasive cancer in the pathological evaluation of hematoxylin and eosin-stained resected breast samples and all ipsilateral lymph node samples after completing neoadjuvant therapy and surgery.	Immediately after the surgery
Relative changes of Ki67 index between Arm A and Arm C	Defined as the geometric mean percentage change in Ki67 index from baseline to post-surgery. For patients with no detectable invasive cancer in the primary site post-surgery, a Ki67 value of 0.01 will be used as a substitute.	Immediately after the surgery
3-year EFS between Arm A and Arm C	Description: Defined as the time from randomization to the first recorded relevant event. Relevant events include preoperative disease progression, postoperative disease recurrence or metastasis, contralateral invasive breast cancer, second primary invasive cancer, and death from any cause.	Following surgery until Year 3
3-year OS between Arm A and Arm C	Defined as the time from randomization to death from any cause. For subjects still alive at the last follow-up, OS is censored at the last follow-up time.	Following surgery until Year 3

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): July 1, 2031

Study Registration Dates

• First Submitted: February 8, 2026
• First Submitted That Met QC Criteria: February 8, 2026
• First Posted (Actual): February 13, 2026

Study Record Updates

• Last Update Posted (Actual): February 18, 2026
• Last Update Submitted That Met QC Criteria: February 14, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; abemaciclib; Imlunestrant
• Other Study ID Numbers: IMPATIENS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No