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

Official title

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.

Overview

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.

Interventions

• 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
• Drug Placebo for Sirolimus for Injection (Albumin-bound)
  IV infusion, every 2 weeks, 4 weeks per treatment cycle

Primary outcome measures

• Progression-free Survival（PFS） [Time frame: Up to ~24 months]

Secondary outcome measures (7)

• Overall Survival（OS） [Time frame: Up to ~36 months]
• Overall response rate（ORR） [Time frame: Up to ~24 months]
• Clinical benefit rate（CBR） [Time frame: Up to ~24 months]
• Disease control rate（DCR） [Time frame: Up to ~24 months]
• Duration of Response（DOR） [Time frame: Up to ~24 months]
• Safety and Tolerability：the incidence and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) [Time frame: Up to ~24 months]
• PK metrics：plasma concentration of sirolimus [Time frame: Up to ~24 months]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 1 center

• Clinical Trials Information Group — Shijiazhuang

Identifiers

NCT: NCT06929325 · HB1901-008

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗