A Study to Evaluate the Pharmacokinetics, Efficacy, and Safety of HLX319 vs. EU-Phesgo® in the Neoadjuvant Therapy of HER2-Positive Early or Locally Advanced Breast Cancer

Official title

A Multicenter, Randomized, Double-Blind, Parallel-Controlled Phase I Clinical Study to Evaluate the Pharmacokinetics, Efficacy, and Safety of Phesgo® Biosimilar HLX319 vs. EU-Phesgo® in the Neoadjuvant Therapy of HER2-Positive Early or Locally Advanced Breast Cancer

Overview

This is a study to compare the similarity in Pharmacokinetics (PK) profile of HLX319 vs. EU-Phesgo® in patients with HER2-positive early or locally advanced breast cancer .

Detailed description

This is a randomized, double-blind, parallel-controlled, multi-center Phase I equivalence study to compare the similarity in PK profile of HLX319 vs. EU-Phesgo® in patients with HER2-positive early or locally advanced breast cancer with a primary tumor \> 2 cm or nodes-positive.

Interventions

• Drug HLX319
  HLX319 is a biosimilar of pertuzumab-trastuzumab monoclonal antibody injection (subcutaneous injection)
• Drug EU-Phesgo®
  EU-Phesgo® is an original marketed drug product, with the generic name pertuzumab-trastuzumab monoclonal antibody injection (subcutaneous injection)

Primary outcome measures

• Peak concentration (Cmax) [Time frame: up to 180 days]
• Area under the serum drug concentration-time curve from 0 to 21 days (AUC0-21d) [Time frame: up to 180 days]
• Steady-state peak concentration (Cmax,ss) [Time frame: up to 180 days]
• Steady-state area under the serum drug concentration-time curve within a dosing interval (AUCss) [Time frame: up to 180 days]

Secondary outcome measures (12)

• Trough concentration (Ctrough) [Time frame: up to 180 days]
• Area under the serum drug concentration-time curve from time 0 to infinity (AUC0-inf) [Time frame: up to 180 days]
• Percentage of extrapolated area in the total AUC (%AUCex) [Time frame: up to 180 days]
• Time to peak concentration (Tmax) [Time frame: up to 180 days]
• Elimination half-life (T1/2) [Time frame: up to 180 days]
• Total clearance (CL/F) [Time frame: up to 180 days]
• Terminal phase distribution volume (Vz/F) [Time frame: up to 180 days]
• Mean residence time (MRT) [Time frame: up to 180 days]
• Steady-state trough concentration (Ctrough,ss) [Time frame: up to 180 days]
• Average steady-state concentration (Caverage,ss) [Time frame: up to 180 days]
• Steady-state time to peak concentration (Tmax,ss) [Time frame: up to 180 days]
• Elimination half-life (T1/2,ss) [Time frame: up to 180 days]

Eligibility criteria

Inclusion criteria

• Voluntary participation in the clinical study and signed the Informed Consent Form (ICF).
• Male or female aged ≥ 18 years old at the time of signing the ICF;
• Histologically confirmed invasive breast cancer, stage II-IIIC, Human Epidermal Growth Factor Receptor 2 (HER2) positive confirmed by central laboratory.
• Participants agree to undergo surgery while meeting the criteria for surgery after neoadjuvant therapy.
• Left ventricular ejection fraction (LVEF) at baseline ≥ 55%.
• An Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0-1.
• Adequate major organ functions.
• Women with child-bearing potential have a negative result of serum pregnancy test at screening period (within 7 days prior to the first dose) or if they are infertile, non- lactating, reproduction-age men and women following highly effective contraceptive measures until 7 months after last dose.

Exclusion criteria

• Stage IV breast cancer, bilateral breast cancer, or multicentric breast cancer.
• History of other malignancy within 5 years.
• Prior systemic therapy for breast cancer treatment or radiotherapy.
• Patients with a history of ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS) who have received systemic therapy or radiotherapy to the ipsilateral breast.
• Patients who have undergone excision biopsy of the primary tumor and/or axillary lymph nodes or lymph node dissection.
• Have severe heart disease or medical conditions.
• Participants with viral hepatitis or those with autoimmune hepatitis, sclerosing cholangitis, or liver cirrhosis.
• Human Immunodeficiency Virus (HIV) infection, HIV antibody positive.
• Daily use of corticosteroid treatment is required.
• Sensitivity to any study medications or any of its ingredients or excipients.
• Participants who underwent any major surgery within 28 days prior to the first dose. Or participants who have received local radiotherapy, radiofrequency ablation, or interventional therapy within 2 weeks prior to the first dose.
• Received another interventional clinical trial therapy within 4 weeks prior to enrollment in the study, or intentionally participated in another interventional clinical trial during the entire study period.
• Severe, uncontrolled systemic diseases that may currently interfere with the therapeutic plan.
• Any other conditions which are inappropriate for the study in the opinion of the investigator.

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

Double blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07601620 · HLX319-BC001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗