A Study of XZP-3287 in Combination With Fulvestrant in Patients With Advanced Breast Cancer

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced Breast Cancer
• Intervention / Treatment: Drug: XZP-3287+Fulvestrant; Drug: Placebo + Fulvestrant

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100025
      • Chinese Academy of Medical Science

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Female patients aged ≥18 years and ≤75 years old;
2. Patient is in the menopausal state；
3. Pathologically-confirmed HR positive and Her2 negative Breast Cancer;
4. 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;
5. At least one measurable lesion (based on RECIST v1.1) or only bone metastases;
6. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1;
7. Adequate organ and marrow function;
8. 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;
9. 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;
10. Patient has signed informed consent before any trial related activities.

Exclusion Criteria:

1. Patient with visceral crisis, inflammatory breast cancer, or brain metastases, except for patient with stable brain metastases;
2. Patient had clinically significant pleural effusions, ascites effusions, or pericardial effusions in the 4 weeks before enrollment;
3. Patient who received prior treatment with mTOR inhibitors, CDK4/6 inhibitors or fulvestrant;
4. Participation in a prior treatment of major surgery, chemotherapy, radiotherapy, and any anti-tumor treatment within 14 days before enrollment；
5. Patient who participated in other clinical trials within 14 days before enrollment or within 5 half-lives of the trial drug, whichever is longer;
6. Patient used CYP3A4 potent inhibitors or potent inducers within 14 days before enrollment or within 5 half-lives of the drug, whichever is longer;
7. 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;
8. Any other malignant tumor has been diagnosed within 3 years before randomization;
9. Patient is in the active stage of HBV, HCV or co-infected with HBV, HCV, or Patient with positive HIV antibody;
10. Patient with severe infection within 4 weeks before enrollment, or unexplained fever> 38.5℃ during screening/before enrollment;
11. Patient with heart function impaired or clinically significant heart disease within 6 months before enrollment;
12. Cerebrovascular accident occurred within 6 months before enrollment, including history of transient ischemic attack or stroke; symptomatic pulmonary embolism;
13. Inability to swallow, intestinal obstruction or other factors that affect the taking and absorption of the drug;
14. Patient with a known hypersensitivity to any of the excipients in this study;
15. A prior history of autologous or allogeneic hematopoietic stem cell transplantation;
16. A prior history of psychotropic drug abuse or drug use;
17. Pregnant or breastfeeding;
18. The researchers considered that there were some cases that were not suitable for inclusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: XZP-3287+Fulvestrant	Drug: XZP-3287+Fulvestrant; 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
Placebo Comparator: Placebo + Fulvestrant	Drug: Placebo + Fulvestrant; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigator-assessed progression free survival (PFS)	An interim analysis will be performed in this study. The primary endpoint of the study is PFS. An interim analysis is scheduled upon the collection of 70%(approximately 125) PFS events, and the final PFS analysis will be conducted after 178 PFS events have been collected.	Up to approximately 24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Disease control rate (DCR)	Up to approximately 24 months
Overall survival (OS)	Up to approximately 5 years
BICR-assessed progression free survival (PFS)	Up to approximately 24 months
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
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

Other Outcome Measures

Outcome Measure	Time Frame
EORTC QLQ-C30 scale	Up to approximately 24 months
EORTC QLQ-BR23 scale	Up to approximately 24 months
EQ-5D-5L scale	Up to approximately 24 months
Plasma ctDNA	Up to approximately 5 months

Collaborators and Investigators

• Sponsor: Xuanzhu Biopharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Binghe Xu, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2021
• Primary Completion (Actual): February 22, 2024
• Study Completion (Estimated): November 1, 2029

Study Registration Dates

• First Submitted: September 18, 2021
• First Submitted That Met QC Criteria: September 30, 2021
• First Posted (Actual): October 14, 2021

Study Record Updates

• Last Update Posted (Actual): May 24, 2024
• Last Update Submitted That Met QC Criteria: May 22, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: XZP-3287; HR positive and Her2 negative; recurrent/metastatic breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Estrogen Antagonists; Estrogen Receptor Antagonists; Fulvestrant
• Other Study ID Numbers: XZP-3287-3001

Drug and device information, study documents

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