Sirolimus for Injection (Albumin-bound) in Combination With Endocrine Therapy for HR+/HER2- Advanced/Metastatic Breast Cancer Patients Who Have Failed Standard Therapy

A Phase II Clinical Trial of the Safety and Efficacy of Sirolimus for Injection (Albumin-bound) in Combination With Endocrine Therapy for the Treatment of HR-positive, HER2-negative Patients With Advanced Breast Cancer Who Have Failed Standard Therapy

This study is a multicenter, open, non-randomized phase II clinical trial consisting of a safety introduction phase followed by a single-arm phase 2 phase. This phase II trial enrolled patients with HR+/HER2- advanced breast cancer who had failed aromatase inhibitor (AI)/fulvestrant ± CDK4/6i. Pts failing prior AI ± CDK4/6i received nab-Sirolimus + fulvestrant, while those failing fulvestrant ± CDK4/6i received nab-Sirolimus + AI.

Study Overview

• Status: Active, not recruiting
• Conditions: HR+/HER2- Advanced/Metastatic Breast Cancer
• Intervention / Treatment: Drug: Sirolimus for Injection (Albumin-bound); Drug: Letrozole; Drug: Anastrozole; Drug: Exemestane; Drug: Fulvestrant

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Cancer Hospital, Chinese Academy of Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. Aged 18 or above, regardless of gender; female patients must be postmenopausal, or premenopausal/perimenopausal.
• 2. Pathologically confirmed HR+, HER2- breast cancer.
• 3. Patients who have failed prior treatment with AI or fulvestrant with or without CDK4/6 inhibitors.
• 4. No more than 3 lines of chemotherapy for inoperable locally advanced or metastatic disease.
• 5. At least one measurable lesion according to RECIST 1.1 criteria. Patients with bone lesions only may be eligible.
• 6. ECOG performance status score of 0-1.
• 7. Investigator-assessed life expectancy ≥3 months.
• 8. Adequate organ and bone marrow function.
• 9. Baseline fasting serum triglyceride <300mg/dL or 3.42mmol/L, fasting serum cholesterol <350mg/dL or 9.07mmol/L
• 10. The baseline fasting plasma glucose (FPG) ˂ 7.8 mmol/L and glycosylated hemoglobin (HbA1c) ˂ 8%
• 11. Premenopausal female patients using LHRH agonists to suppress ovarian function must agree to use two acceptable forms of highly effective contraception during the study and for 6 months after stopping study treatment; female patients of childbearing potential must have a negative pregnancy test before starting study treatment and must not be breastfeeding.
• 12. Male patients must agree to use barrier contraception (i.e., condoms) during the study and for 6 months after stopping study treatment; for men with future fertility plans, sperm freezing is recommended before starting study treatment.
• 13. Participants must provide informed consent before the trial and voluntarily sign the written ICF.

Exclusion Criteria:

• 1. Previous pathological diagnosis of HER2-positive breast cancer.
• 2. Patients judged by the investigator to be unsuitable for endocrine therapy.
• 3. Patients who have previously received PI3K/AKT/mTOR inhibitors.
• 4. Received chemotherapy, radiotherapy, biological therapy, targeted therapy, immunotherapy, or other anti-tumor treatments within 4 weeks before randomization.
• 5. Received other unapproved investigational drugs within 4 weeks before randomization.
• 6. Underwent major surgery within 4 weeks before randomization or has not fully recovered from any previous invasive procedures.
• 7. Received systemic glucocorticoids (prednisone >10 mg/day or equivalent) or other immunosuppressive treatments within 2 weeks before randomization.
• 8. Had an infection within 2 weeks before randomization requiring systemic (oral or IV) anti-infective treatment (uncomplicated urinary tract infections or upper respiratory tract infections excluded).
• 9. Received inactivated or live attenuated vaccines or COVID-19 vaccines within 4 weeks before randomization.
• 10. Used strong inhibitors or inducers of CYP3A4 hepatic metabolic enzymes within 2 weeks before randomization or still need to continue using such drugs.
• 11. Diagnosed with other malignancies within 5 years before randomization.
• 12. Suffering from severe cardiovascular or cerebrovascular diseases.
• 13. Adverse reactions from previous anti-tumor treatments have not recovered to CTCAE 5.0 grade ≤1.
• 14. Active leptomeningeal disease or poorly controlled central nervous system metastases.
• 15. Presence of pleural/abdominal effusion or pericardial effusion with clinical symptoms or requiring symptomatic treatment.
• 16. Known bleeding tendency (constitution) or coagulation disorders.
• 17. History of severe lung diseases such as interstitial lung disease and/or pneumonia, pulmonary hypertension, or radiation pneumonitis requiring glucocorticoid treatment.
• 18. Known hypersensitivity or intolerance to any component of the study drug or its excipients, or LHRH agonists (if applicable).
• 19. History of autoimmune diseases (except tuberous sclerosis), immunodeficiency diseases, including HIV-positive, or other acquired or congenital immunodeficiency diseases, or organ transplant history.
• 20. Active HBV, HCV, syphilis, or tuberculosis infection.
• 21. Other conditions judged by the investigator to be unsuitable for participation in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Sirolimus for Injection (Albumin-bound) Combined with Fulvestrant or Aromatase Inhibitor; A: Sirolimus for Injection (Albumin-bound) Combined with Fulvestrant; B: Sirolimus for Injection (Albumin-bound) Combined with Exemestane，or Letrozole，or Anastrozole.

Drug: Sirolimus for Injection (Albumin-bound); IV infusion, every 2 weeks, 4 weeks per treatment cycle; Drug: Letrozole; Oral administration at a dose of 2.5 mg once daily for a 4-week cycle; Drug: Anastrozole; Oral administration at a dose of 1 mg once daily for a 4-week cycle; Drug: Exemestane; Oral administration at a dose of 25 mg once daily with a meal every 4 weeks; Drug: Fulvestrant; Fulvestrant: IM injection, 500 mg, on day 1 and day 15 of Cycle 1, and then on day 1 of each cycle thereafter, 4 weeks per treatment cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Objective Response Rate (ORR)	Up to ~24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Disease Control Rate (DCR）	Up to ~36 months
Duration of Response (DoR)	Up to ~24 months
Progression-Free Survival (PFS)	Up to ~24 months
Overall Survivial (OS)	Up to ~24 months
Safety and Tolerability :the incidence and severity of Treatment Emergent Adverse Events（TEAEs）and Treatment-Related Adverse Events（TRAEs）	Up to ~24 months
PK parameter: the concentration of sirolimus	Up to ~24 months

Collaborators and Investigators

• Sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): February 29, 2024
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: April 26, 2025
• First Submitted That Met QC Criteria: April 26, 2025
• First Posted (Actual): May 4, 2025

Study Record Updates

• Last Update Posted (Actual): May 4, 2025
• Last Update Submitted That Met QC Criteria: April 26, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antineoplastic; Antineoplastic Agents; Antifungal Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Enzyme Inhibitors; Steroid Synthesis Inhibitors; Hormone Antagonists; Estrogen Receptor Antagonists; Estrogen Antagonists; Aromatase Inhibitors; Letrozole; Fulvestrant; Anastrozole; Sirolimus; Exemestane
• Other Study ID Numbers: HB1901-005

Drug and device information, study documents

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