A Study of XZP-3287 in Combination With Letrozole/Anastrozole in Patients With Advanced Breast Cancer

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

This is a Phase III clinical trial designed to evaluate the efficacy and safety of XZP-3287 in combination with Letrozole/Anastrozole versus placebo in combination with Letrozole/Anastrozole in patients with HR-positive and HER2-negative recurrent/metastatic breast cancer who have not received systemic anticancer therapy.

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced Breast Cancer
• Intervention / Treatment: Drug: XZP-3287+ Letrozole/Anastrozole; Drug: Placebo + Letrozole/Anastrozole

• Study Type: Interventional
• Enrollment (Anticipated): 372
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Cuilan Xiao; Phone Number: (+86)13699167610; Email: xiaocuilan@xuanzhubio.com

Study Locations

• China
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150081
      • Harbin Medical University Cancer Hospital
      • Contact: Qingyuan Zhang; Phone Number: (+86)13313612989; Email: 13313612989@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Female patients aged ≥18 years and ≤75 years old;
2. Patient is in the menopausal state；
3. Histologically or cytologically confirmed locally advanced, recurrent or metastatic breast cancer, which was pathologically confirmed to be HR-positive and HER2-negative;
4. Evidence of locally advanced, recurrent, or metastatic disease that is not amenable to curative surgical resection or radiation therapy and is not clinically amenable to chemotherapy;
5. No prior systemic anticancer therapy for locally advanced, recurrent, or metastatic disease;
6. At least one measurable lesion (based on RECIST v1.1) or only bone metastases;
7. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1;
8. Adequate organ and marrow function;
9. Patient of childbearing age must undergo a serum pregnancy test within 7 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;
10. 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;
11. Patient has signed informed consent before any trial related activities.

Exclusion Criteria:

1. Patients with disease recurrence or metastasis at or within 12 months after previous neoadjuvant or adjuvant therapy with endocrine drugs;
2. Patient with visceral crisis or brain metastases, except for patient with stable brain metastases;
3. Patient had clinically significant pleural effusions, ascites effusions, or pericardial effusions in the 4 weeks before enrollment;
4. Patient who received prior treatment with mTOR inhibitors or CDK4/6 inhibitors ;
5. Participation in a prior treatment of major surgery, chemotherapy, radiotherapy, and any anti-tumor treatment within 14 days before enrollment；
6. Patient who participated in other clinical trials within 14 days before enrollment or within 5 half-lives of the trial drug, whichever is longer;
7. Patient used CYP3A4 potent inhibitors or potent inducers within 14 days before enrollment or within 5 half-lives of the drug, whichever is longer;
8. Initiation of bisphosphonates or RANKL inhibitors within 7 days before enrollment, and subjects who have initiated treatment > 7 days before enrollment should not change the method of use;
9. Any other malignant tumor has been diagnosed within 5 years before randomization;
10. Patient is in the active stage of HBV, HCV or co-infected with HBV, HCV, or Patient with positive HIV antibody;
11. Patient with severe infection within 4 weeks before enrollment, or unexplained fever> 38.3℃ during screening/before enrollment;
12. Patient with heart function impaired or clinically significant heart disease within 6 months before enrollment;
13. Cerebrovascular accident occurred within 6 months before enrollment, including history of transient ischemic attack or stroke; pulmonary embolism;
14. Inability to swallow, intestinal obstruction or other factors that affect the taking and absorption of the drug;
15. Patient with a known hypersensitivity to any of the excipients in this study;
16. A prior history of autologous or allogeneic hematopoietic stem cell transplantation;
17. A prior history of psychotropic drug abuse or drug use;
18. Nursing Mothers;
19. 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+ Letrozole/Anastrozole	Drug: XZP-3287+ Letrozole/Anastrozole; XZP-3287 360 mg orally after meals Twice daily of every 28-day cycle; Letrozole tablets 2.5mg orally once daily of every 28-day cycle or Anastrozole tablets 1mg orally once daily of every 28-day cycle
Placebo Comparator: Placebo + Letrozole/Anastrozole	Drug: Placebo + Letrozole/Anastrozole; Placebo 360 mg orally after meals Twice daily of every 28-day cycle; Letrozole tablets 2.5mg orally once daily of every 28-day cycle or Anastrozole tablets 1mg orally once daily of every 28-day cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Investigator-assessed progression free survival (PFS)	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	Measure Description	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
Time to Deterioration（TTD）	Time from randomization to the first worsening of the EORTC QLQ-C30 scale score.	Up to approximately 24 months

Collaborators and Investigators

• Sponsor: Xuanzhu Biopharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Qingyuan Zhang, Harbin Medical University

Study record dates

Study Major Dates

• Study Start (Anticipated): February 1, 2022
• Primary Completion (Anticipated): December 1, 2024
• Study Completion (Anticipated): December 1, 2025

Study Registration Dates

• First Submitted: February 16, 2022
• First Submitted That Met QC Criteria: February 16, 2022
• First Posted (Actual): February 25, 2022

Study Record Updates

• Last Update Posted (Actual): February 25, 2022
• Last Update Submitted That Met QC Criteria: February 16, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: XZP-3287; HR positive Her2 negative recurrent/metastatic breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Letrozole; Anastrozole
• Other Study ID Numbers: XZP-3287-3002

Drug and device information, study documents

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