Sirolimus for Injection (Albumin-bound) Combined With Fulvestrant for HR+/HER2- Advanced/Metastatic Breast Cancer Patients Previously Treated With CDK4/6 Inhibitors

A Randomized, Double-blind, Multicenter Phase III Clinical Study to Evaluate the Efficacy and Safety of Sirolimus for Injection (Albumin-bound) Combined With Fulvestrant Versus Placebo Combined With Fulvestrant in HR-positive, HER2-negative Locally Advanced or Metastatic Breast Cancer Patients After Prior CDK4/6 Inhibitor Treatment.

A randomized, double-blind, multicenter phase III clinical study to evaluate the efficacy and safety of sirolimus for injection (albumin-bound) combined with fulvestrant in patients with HR+ and HER2- advanced breast cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: HR+/HER2- Advanced/Metastatic Breast Cancer
• Intervention / Treatment: Drug: Sirolimus for Injection (Albumin-bound); Drug: Fulvestrant Injection; Drug: Placebo for Sirolimus for Injection (Albumin-bound)

• Study Type: Interventional
• Enrollment (Estimated): 312
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Clinical Trials Information Group officer; Phone Number: 86-0311-69085587; Email: ctr-contact@cspc.cn

Study Locations

• China
  • Hebei
    • Shijiazhuang, Hebei, China
      • Clinical Trials Information Group
      • Contact: Clinical Trials Information Group officer; Phone Number: 86-0311-69085587; Email: ctr-contact@cspc.cn

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. Locally advanced or metastatic breast cancer, not suitable for curative surgery or radiotherapy, and no current clinical indication for chemotherapy.
• 4. Previously received at least one, up to two lines of systemic therapy (including at least one line of endocrine therapy combined with CDK4/6 inhibitor therapy).
• 5. At least one measurable lesion according to RECIST 1.1 criteria.
• 6. Willing to provide tumor and/or blood samples for biomarker testing; if unable to provide, subject to investigator and sponsor evaluation for eligibility.
• 7. ECOG performance status score of 0-1.
• 8. Investigator-assessed life expectancy ≥6 months.
• 9. Adequate organ and bone marrow function.
• 10. 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 2 years after stopping study treatment; female patients of childbearing potential must have a negative pregnancy blood test before starting study treatment and must not be breastfeeding.
• 11. Male patients must agree to use barrier contraception (i.e., condoms) during the study and for 2 years after stopping study treatment; for men with future fertility plans, sperm freezing is recommended before starting study treatment.
• 12. 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, fulvestrant, or other ER-targeted therapies (including oral SERDs, ER protein degraders PROTAC, etc.).
• 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: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sirolimus for Injection (Albumin-bound) Combined with Fulvestrant	Drug: Sirolimus for Injection (Albumin-bound); IV infusion, every 2 weeks, 4 weeks per treatment cycle; Drug: Fulvestrant Injection; 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
Active Comparator: Placebo Combined with Fulvestrant	Drug: Fulvestrant Injection; 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; Drug: Placebo for Sirolimus for Injection (Albumin-bound); IV infusion, every 2 weeks, 4 weeks per treatment cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression-free Survival（PFS）	Up to ~24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall Survival（OS）	Up to ~36 months
Overall response rate（ORR）	Up to ~24 months
Clinical benefit rate（CBR）	Up to ~24 months
Disease control rate（DCR）	Up to ~24 months
Duration of Response（DOR）	Up to ~24 months
Safety and Tolerability：the incidence and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)	Up to ~24 months
PK metrics：plasma 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 (Estimated): April 1, 2025
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: April 8, 2025
• First Submitted That Met QC Criteria: April 14, 2025
• First Posted (Actual): April 16, 2025

Study Record Updates

• Last Update Posted (Actual): April 16, 2025
• Last Update Submitted That Met QC Criteria: April 14, 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; Protein Kinase Inhibitors; Hormone Antagonists; Estrogen Receptor Antagonists; Estrogen Antagonists; Fulvestrant; MTOR Inhibitors; Sirolimus; Temsirolimus
• Other Study ID Numbers: HB1901-008

Drug and device information, study documents

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