HER2 + Breast Cancer
Conditions
Brief summary
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
DRUGHLX319
HLX319 is a biosimilar of pertuzumab-trastuzumab monoclonal antibody injection (subcutaneous injection)
DRUGEU-Phesgo®
EU-Phesgo® is an original marketed drug product, with the generic name pertuzumab-trastuzumab monoclonal antibody injection (subcutaneous injection)
Sponsors
Shanghai Henlius Biotech
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peak concentration (Cmax) | up to 180 days | Peak concentration after a single drug administration in Cycle 1. |
| Area under the serum drug concentration-time curve from 0 to 21 days (AUC0-21d) | up to 180 days | Area under the serum drug concentration-time curve from 0 to 21 days after a single drug administration in Cycle 1. |
| Steady-state peak concentration (Cmax,ss) | up to 180 days | The steady-state peak concentration after multiple doses administration in Cycle 4. |
| Steady-state area under the serum drug concentration-time curve within a dosing interval (AUCss) | up to 180 days | Steady-state area under the serum drug concentration-time curve within a dosing interval after multiple doses administration in Cycle 4. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Trough concentration (Ctrough) | up to 180 days | Trough concentration after a single dose administration |
| Area under the serum drug concentration-time curve from time 0 to infinity (AUC0-inf) | up to 180 days | Area under the serum drug concentration-time curve from time 0 to infinity after a single dose administration |
| Percentage of extrapolated area in the total AUC (%AUCex) | up to 180 days | Percentage of extrapolated area in the total AUC after a single dose administration |
| Time to peak concentration (Tmax) | up to 180 days | time to peak concentration after a single dose administration |
| Elimination half-life (T1/2) | up to 180 days | elimination half-life after a single dose administration |
| Total clearance (CL/F) | up to 180 days | total clearance after a single dose administration |
| Terminal phase distribution volume (Vz/F) | up to 180 days | terminal phase distribution volume after a single dose administration |
| Mean residence time (MRT) | up to 180 days | mean residence time after a single dose administration |
| Steady-state trough concentration (Ctrough,ss) | up to 180 days | steady-state trough concentration after multiple doses administration in Cycle 4 |
| Average steady-state concentration (Caverage,ss) | up to 180 days | average steady-state concentration after multiple doses administration in Cycle 4 |
| Steady-state time to peak concentration (Tmax,ss) | up to 180 days | steady-state time to peak concentration after multiple doses administration in Cycle 4 |
| Elimination half-life (T1/2,ss) | up to 180 days | elimination half-life after multiple doses administration in Cycle 4 |
| Steady-state volume of distribution (Vss/F) | up to 180 days | steady-state volume of distribution after multiple doses administration in Cycle 4 |
| Steady-state total clearance (CLss/F) | up to 180 days | steady-state total clearance after multiple doses administration in Cycle 4 |
| accumulation ratio based on Cmax (RCmax) | up to 180 days | accumulation ratio based on Cmax after multiple doses administration in Cycle 4 |
| Accumulation ratio based on AUC (RAUC) | up to 180 days | accumulation ratio based on AUC after multiple doses administration in Cycle 4 |
| The total pathological complete response (tpCR) rate assessed by the investigator | up to 180 days | — |
| Breast pathologic complete response (bpCR) rate assessed by the investigator | up to 180 days | — |
| Objective response rate (ORR) assessed by the investigator | up to 180 days | according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria |
| Incidence and severity of adverse events (AEs) | up to 180 days | severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 6.0 |
| Number of participants with abnormal vital signs | up to 180 days | Detailed Outcome Measure will be defined in the Statistical Analysis Plan |
| Number of participants with abnormal physical examination findings | up to 180 days | Detailed Outcome Measure will be defined in the Statistical Analysis Plan |
| Number of participants with abnormal Laboratory tests results | up to 180 days | Detailed Outcome Measure will be defined in the Statistical Analysis Plan |
| Number of participants with abnormal 12-lead ECG readings | up to 180 days | Detailed Outcome Measure will be defined in the Statistical Analysis Plan |
| Positivity rates of anti-drug antibodies (ADA) | up to 180 days | — |
| Positivity rates of neutralizing antibodies (NAb) | up to 180 days | — |
Contacts
CONTACTQi Jin
Outcome results
None listed