A Phase Ⅲ Study of the Efficacy and Safety of Hemay022+Aromatase Inhibitor(AI) in Participants With ER+/HER2+ Advanced or Metastatic Breast Cancer

Study Overview
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Brief Summary
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This is a Phase III, randomized, multicenter, 2-arm, open-label clinical trial designed to compare the safety and efficacy of Hemay022+Aromatase inhibitor(AI) with that of capecitabine + lapatinib in participants with ER+/HER2+ locally advanced or metastatic breast cancer. Participants will be treated until disease progression (PD), unmanageable toxicity, or study termination. Once disease progression is reported, all participants will be followed for survival every 3 months until death, loss to follow-up.

Official Title
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A Randomized, Multicenter, Parallel,Phase III Open-label Study of the Efficacy and Safety of Hemay022 + AI in Patients With ER+/HER2+ Advanced or Metastatic Breast Cancer Who Have Received Prior Trastuzumab-Based Therapy

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Hemay022+AI
* Drug: Lapatinib+Capecitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years old； Subjects must give informed consent to the study before the study entry and voluntarily sign a written informed consent form; Breast cancer subjects diagnosed by pathology; ER positive and HER2 over-expression; Advanced/metastatic breast cancer that has previously received treatment failure with trastuzumab (or trastuzumab biosimilar) regimen; Measurable and/or nonmeasurable disease; (Eastern Cooperative Oncology Group)ECOG Performance Status of 0-1; The estimated survival time is more than 3 months; Postmenopausal women; Adequate bone marrow, liver, kidney, and coagulation Bone Marrow Function; All previous treatment-related toxicities must be Common Terminology Criteria of Adverse Events (CTCAE ,version 5.0) ≤ Grade 2 at the time of randomization, except for hair loss, pigmentation, and long-term toxicity caused by radiotherapy (which cannot be recovered by the investigator's judgment)； Women patients of childbearing age (including their partners) have no pregnancy plan and voluntarily take effective contraceptive measures from the signing of the informed consent form to 3 months after the last medication. Exclusion Criteria: Patients with visceral crisis; Patients with the presence of spinal cord compression or brain, meningeal metastases; Patients who have been treated with a small molecule HER2 tyrosine kinase inhibitor (HER2-TKI) (medication course ≤2 weeks is excluded) Have received radiotherapy within 4 weeks prior to study； Have received chemotherapy for advanced breast cancer> 1 lines ; Patients with parenteral nutrition; malabsorption syndrome; or any condition possibly affecting drug absorption or inability to tolerate oral medications; Use of any drug that inhibits or induces hepatic metabolism of Hemay022 within 2 weeks prior to study and entire study duration; Patients who are known to have a history of allergies to Hemay022, lapatinib、AI (letrozole, exemestane) capecitabine or similar drugs; Left ventricular ejection fraction (LVEF) <50％; Positive blood for human immunodeficiency virus (HIV antibody); Positive hepatitis B surface antigen and HBV-DNA>upper limit of normal; Active hepatitis C virus (HCV) infection Patients with active infection requiring intravenous anti-infective treatment Arrhythmias requiring treatment ; Confirmed QTc prolongation (≥500ms) ; People with a history of interstitial lung disease that needs treatment, a history of radiation pneumonitis, or clinically active interstitial lung disease Have received other clinical trial drugs within 4 weeks before the study Major surgery or injury less than 4 weeks before the study The study period must be accompanied by other antitumor therapy，such as chemotherapy, targeted therapy, hormone therapy, immunotherapy, radiotherapy (except symptomatic local radiotherapy) Any other malignant cancer within 5 years with the exception of adequately treated cervical cancer in situ or basal and squamous cutaneous cell carcinomas Any condition that would make the subject inappropriate for this study by the investigator's judgment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hemay022 and AI<br>Hemay022 in combination with AI will be taken orally once daily. Planned dose of Hemay022 will be 500mg daily for 21 days. | Drug: Hemay022+AI<br>* hemay022：orally once daily，A 21-day cycle<br>|
| Active Comparator: Lapatinib and Capecitabine<br>lapatinib in combination with capecitabine will be taken in suitable dose until disease progression or death, etc. | Drug: Lapatinib+Capecitabine<br>* Take the pills according to the instructions<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median progression-free survival（mPFS）based on Independent Review Committee (IRC) assessment according to RECIST v1.1 | PFS defined as the proportion of patients alive and without progression | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) of the two group according to RECIST v1.1 | OS is defined as the time from random to any cause of death | From date of randomization until the date of death from any cause, whichever came first,assessed up to 36 months | 
| Objective response rate ( ORR, partial response rate+ complete response rate) according to RECIST v1.1 | ORR defined as the proportion of subjects in complete response (CR) or (partial response) PR | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 month | 
| Clinical benefit rate (CBR) according to RECIST v1.1 | Clinical benefit rate defined as percentage of patients with stable disease (SD) ≥ 6 months/partial response (PR)/complete response (CR) | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 month | 
| Duration of Response (DOR) according to RECIST v1.1 | DOR defined as the duration after the first assessment as CR or PR, only applicable to subjects who have achieved remission | From the first recorded CR or PR until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 month | 
| Time to Response (TTR) | TTR defined as the time from random to CR or PR for the first time | From date of randomization until the date of the first recorded CR or PR assessed up to 36 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Cancer; ER+; HER2+;