A Study of XZP-3287 in Combination With Fulvestrant in Patients With Advanced 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 XZP-3287 in combination with Fulvestrant versus placebo combined with Fulvestrant in Patients who have HR positive and Her2 negative recurrent/metastatic breast cancer and have received prior endocrine therapy are eligible for study.

Official Title
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A Phase III Study to Evaluate the Efficacy and Safety of XZP-3287 in Combination With Fulvestrant Versus Placebo Combined With Fulvestrant in Patients With HR Positive and HER2 Negative Recurrent/Metastatic Breast Cancer

Conditions
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Advanced Breast Cancer

Intervention / Treatment
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* Drug: XZP-3287+Fulvestrant
* Drug: Placebo + Fulvestrant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female patients aged ≥18 years and ≤75 years old; Patient is in the menopausal state； Pathologically-confirmed HR positive and Her2 negative Breast Cancer; Locally advanced stage, recurrence or metastasis breast cancer; 4.1 Disease progression after previous endocrine therapy； 4.2 One previous line of chemotherapy for advanced/metastatic disease is allowed in addition to endocrine therapy; At least one measurable lesion (based on RECIST v1.1) or only bone metastases; Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1; Adequate organ and marrow function; Patient of childbearing age must undergo a serum pregnancy test within 14 days before randomization, and the result is negative; patient is willing to use a medically approved high-efficiency contraceptive method during the study period and within 6 months after the last study drug treatment; Patient with acute toxic reactions caused by previous anti-tumor treatments or surgical operations were alleviated to grade 0 to 1 (NCI-CTCAE v5.0), or to the level specified by the enrollment criteria; Patient has signed informed consent before any trial related activities. Exclusion Criteria: Patient with visceral crisis, inflammatory breast cancer, or brain metastases, except for patient with stable brain metastases; Patient had clinically significant pleural effusions, ascites effusions, or pericardial effusions in the 4 weeks before enrollment; Patient who received prior treatment with mTOR inhibitors, CDK4/6 inhibitors or fulvestrant; Participation in a prior treatment of major surgery, chemotherapy, radiotherapy, and any anti-tumor treatment within 14 days before enrollment； Patient who participated in other clinical trials within 14 days before enrollment or within 5 half-lives of the trial drug, whichever is longer; Patient used CYP3A4 potent inhibitors or potent inducers within 14 days before enrollment or within 5 half-lives of the drug, whichever is longer; Patient who used bisphosphonates or RANKL inhibitors within 7 days before enrollment, patient who have started treatment during the study should not change the method of use; Any other malignant tumor has been diagnosed within 3 years before randomization; Patient is in the active stage of HBV, HCV or co-infected with HBV, HCV, or Patient with positive HIV antibody; Patient with severe infection within 4 weeks before enrollment, or unexplained fever> 38.5℃ during screening/before enrollment; Patient with heart function impaired or clinically significant heart disease within 6 months before enrollment; Cerebrovascular accident occurred within 6 months before enrollment, including history of transient ischemic attack or stroke; symptomatic pulmonary embolism; Inability to swallow, intestinal obstruction or other factors that affect the taking and absorption of the drug; Patient with a known hypersensitivity to any of the excipients in this study; A prior history of autologous or allogeneic hematopoietic stem cell transplantation; A prior history of psychotropic drug abuse or drug use; Pregnant or breastfeeding; The researchers considered that there were some cases that were not suitable for inclusion.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: XZP-3287+Fulvestrant<br> | Drug: XZP-3287+Fulvestrant<br>* XZP-3287 360 mg orally Twice daily(Q12H) of every 28-day cycle Fulvestrant 500mg intramuscular injection on day 1 and day 15 for the first cycle and then on day 1 for every cycle (28-day) until progressive disease<br>|
| Placebo Comparator: Placebo + Fulvestrant<br> | Drug: Placebo + Fulvestrant<br>* Placebo 360 mg orally Twice daily(Q12H) of every 28-day cycle Fulvestrant 500mg intramuscular injection on day 1 and day 15 for the first cycle and then on day 1 for every cycle (28-day) until progressive disease<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigator-assessed progression free survival (PFS) |  | Up to approximately 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BICR-assessed progression free survival (PFS) |  | Up to approximately 24 months | 
| Overall survival (OS) |  | Up to approximately 5 years | 
| Overall survival rate(OSR) |  | Up to approximately 5 years | 
| Objective response rate (ORR) |  | Up to approximately 24 months | 
| Duration of response (DoR) |  | Up to approximately 24 months | 
| Disease control rate (DCR) |  | Up to approximately 24 months | 
| Clinical benefit rate (CBR) |  | Up to approximately 24 months | 
| Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 |  | Up to approximately 24 months | 
| Number of participants with treatment emergent adverse events as assessed by CTCAE v5.0 |  | Up to approximately 24 months | 
| Maximum Plasma Concentration [Cmax] |  | Up to approximately 4 months | 
| Time to Maximum Plasma Concentration [Tmax] |  | Up to approximately 4 months | 
| Area under the time-concentration Curve [AUC] |  | Up to approximately 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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XZP-3287, HR positive and Her2 negative, recurrent/metastatic breast cancer