A Study of BPI-16350 in Combination With Fulvestrant in Patients With HR+ and HER2- Locally Advanced, Recurrent or Metastatic Breast Cancer

Study Overview
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Brief Summary
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This is a phase III clinical trial to evaluate the efficacy and safety of BPI-16350 in combination with Fulvestrant versus placebo combined with Fulvesrant in Patients who have HR positive and HER2 negative locally advanced，recurrent or metastatic breast cancer with disease progression following endocrine therapy.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Compare Fulvestrant Plus BPI-16350 or Plus Placebo in Patients With HR+, HER2- Locally Advanced, Recurrent or Metastatic Breast Cancer With Disease Progression Following Endocrine Therapy

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: BPI-16350
* Drug: placebo
* Drug: Fulvestrant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has the pathologically-confirmed diagnosis of locally advanced, recurrent or metastatic, HR positive, HER2 negative Breast Cancer One previous line of chemotherapy for advanced/metastatic disease is allowed Disease Progression following endocrine therapy Have postmenopausal status Have 1 of the following, as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1: measurable disease or nonmeasurable bone-only disease ECOG: 0 1 Adequate organ function Exclusion Criteria: Previous treatment with cytotoxic drugs within 4 weeks before enrollment Previous treatment with endocrine or small molecule drug tyrosine kinase inhibitor TKI within 2 weeks before enrollment Patients who received prior treatment with any CDK4/6 inhibitor, everolimus or fulvestant HER2 positive Patients with major surgery within 4 weeks, severe or unstable systemic disease, unstable/symptomatic CNS metastasis, other malignant tumors, ILD, clinical significant cardiac disease, bleeding or embolic disease, active infectious disease, conditions affecting drug swallow and absorption, etc Pregnancy or lactation Other conditions considered not appropriate to participate in this trial by the investigators

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: experimental group<br>Intervention Drug: BPI-16350, Fulvestrant | Drug: BPI-16350<br>* BPI-16350 400 mg, orally once daily<br>Drug: Fulvestrant<br>* Fulvestrant 500 mg intramuscular injection on day 1 and day 15 for the first cycle and then on day 1 for every cycle until progressive disease<br>|
| Placebo Comparator: control group<br>Intervention Drug: Placebo, Fulvestrant | Drug: placebo<br>* Placebo 400 mg, orally once daily<br>Drug: Fulvestrant<br>* Fulvestrant 500 mg intramuscular injection on day 1 and day 15 for the first cycle and then on day 1 for every cycle until progressive disease<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigator-assessed PFS | The PFS time is measured from the date of randomization to the date of objective progression or the date of death due to any cause, whichever is earlier. | up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IREC-assessed PFS | The PFS time is measured from the date of randomization to the date of objective progression or the date of death due to any cause, whichever is earlier. | up to 3 years | 
| ORR | The proportion of patients with CR or PR according to RECIST v1.1 | up to 3 years | 
| DCR | The proportion of patients with CR, PR, or SD according to RECIST v1.1 | up to 3 years | 
| DOR | The time from the date of first evidence of a CR or PR to the date of objective progression or death from any cause, whichever is earlier | up to 3 years | 
| CBR | The proportion of patients with CR, PR, or SD ≥6 months according to RECIST v1.1 | up to 3 years | 
| OS | The time from the date of randomization to the date of death from any cause | up to 5 years | 
| AEs and SAEs | Number of Participants With adverse events (AEs) and serious adverse events (SAEs) Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v5.0 | up to 3 years | 
| EORTC QLQ-C30 | Changes in scores from baseline using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | up to 5 years | 
| Evaluate the pharmacokinetics of BPI-16350 | Based on blood plasma concentration. | Up to 3 cycles(each cycle is 28 days) |