HER2-positive Breast Cancer
Conditions
Brief summary
A randomized, multicenter, Phase I/IIa clinical study to evaluate the tolerability, safety, efficacy, pharmacokinetics and immunogenicity after single/multiple administration of recombinant anti-HER2 humanized monoclonal antibody for injection for the treatment of HER2-positive breast cancer patients.
Interventions
BIOLOGICALGB221,2 mg/kg
Single dose, 2mg/kg group: lyophilized powder of Coprelotamab Injection; strength 110mg/bottle; 2 mg/kg for one dose, intravenous infusion, completed for over 90 minutes
BIOLOGICALGB221,6 mg/kg
Single dose 6mg/kg group: lyophilized powder of Coprelotamab Injection; strength 110mg/bottle; 6 mg/kg for one dose, intravenous infusion, completed for over 90 minutes
BIOLOGICALHerceptin,6 mg/kg
Single dose group: lyophilized powder of Trastuzumab Injection; strength 440 mg/bottle; 6 mg/kg for one dose, intravenous infusion, completed for over 90 minutes
BIOLOGICALGB221,8mg/kg
Single dose 8mg/kg group: lyophilized powder of Coprelotamab Injection; strength 110mg/bottle; 8mg/kg for one dose, intravenous infusion, completed for over 90 minutes
BIOLOGICALGB221:2mg/kg and Capecitabi:1000mg/kg
GB221:Lyophilized powder of Coprelotamab Injection; strength 110mg/bottle; 2mg/kg, the first infusion is completed over 90 minutes. If no serious adverse reaction is observed, the subsequent infusion can be completed over 30 minutes. The administration shall be continued until disease progression or intolerable toxic reactions or ICF withdrawal of subjects. Multiple dose group; Capecitabine:1000mg/kg, orally twice daily (one dose each in the morning and evening; total daily dose of 2000 mg/m2), administration for 2 weeks followed by a 1-week rest period, as a 3-week cycle.
BIOLOGICALHerceptin:2mg/kg and Capecitabin:1000mg/kg
Herceptin:Lyophilized powder of Trastuzumab Injection; strength 440 mg/bottle; 2mg/kg, the first infusion is completed over 90 minutes. If no serious adverse reaction is observed, the subsequent infusion can be completed over 30 minutes. The administration shall be continued until disease progression or intolerable toxic reactions or ICF withdrawal of subjects. Multiple dose groups; Capecitabine:1000mg/kg, orally twice daily (one dose each in the morning and evening; total daily dose of 2000 mg/m2), administration for 2 weeks followed by a 1-week rest period, as a 3-week cycle.
Sponsors
Genor Biopharma Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
For single dose: Inclusion Criteria: 1. Aged 18 to 65 years; 2. Histopathologically confirmed breast cancer; 3. HER-2 positive (definition: the immunohistochemistry (IHC) test of pathological samples showed HER-2 +++ or immunohistochemistry (IHC) test showed HER-2 ++ and positive FISH amplification test); 4. HER2-positive breast cancer patients who have no lesion after surgery and never received anti-HER-2 treatment; 5. The investigators consider that the subject has recovered from the toxic reactions caused by the previous chemotherapy 4 weeks after the last chemotherapy. 6. The expected survival is 3 months or longer; 7. ECOG performance status is 0, 1 or 2; 8. The left ventricular ejection fraction (LVEF)≥50%; 9. The major organ function is normal and laboratory tests meet relevant criteria: l Hematology test: * Hb≥90 g/L (no blood transfusion within 14 days); * ANC≥1.5×109 /L; * PLT≥100×109 /L; l Hepatic and renal function tests: * TBIL≤1.5×ULN (upper limit of normal); * ALT and AST≤2.5×ULN; * Serum Cr ≤ULN; 10. Normal coagulation function test; 11. Voluntarily sign the written informed consent form
Exclusion criteria
1. Pregnant or breastfeeding females; or women of childbearing potential who have positive urine pregnancy test; or any subjects who are able to bear or father a child but cannot or are unwilling to adopt medically acceptable effective contraceptive methods during the study period and within 3 months after the end of the study; 2. Subjects who have any of the following cardiac conditions: * Unstable angina pectoris; * Medical history of congestive heart failure; * Previous medical history of myocardial infarction, coronary artery bypass grafting or coronary stent implantation; * Clinically significant pericardial diseases and valvular heart diseases; * Serious uncontrolled arrhythmia; * Any other cardiac diseases which may cause safety risks for patients if they are enrolled in this study; 3. Uncontrolled hypertension (defined as screening systolic blood pressure ≥ 180mmHg and/or diastolic blood pressure ≥110mmHg); 4. Known HIV, HBV or HCV infection; 5. Allergic constitution; known allergic to the components of the investigational product; 6. Have drug abuse history or alcohol addiction history; 7. Participated in other clinical studies within 4 weeks before the initiation of the study; 8. Have complicated diseases which may interfere with study participation or evaluation at the discretion of the investigator, e.g., uncontrolled infection, coagulation disorders and other diseases, or the investigators consider that participation in this study may lead to greater risks for patients. For multiple dose groups: Inclusion Criteria: 1. Aged 18 to 65 years; 2. Histopathologically confirmed breast cancer; 3. HER-2 positive (definition: the immunohistochemistry (IHC) test of pathological samples showed HER-2 +++ or immunohistochemistry (IHC) test showed HER-2 ++ and positive FISH amplification test); 4. Patients with metastatic breast cancer who failed to respond to previous chemotherapy and no more than three lines, and never received anti-HER-2 treatment(subjects in single dose group who experienced disease progression but meet other inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| K e | Up to 5 weeks | K e |
| CL/F | Up to 5 weeks | CL/F |
| T 1/2 | Up to 5 weeks | T 1/2 |
| maximum tolerated dose,MTD | Up to 5 weeks | To evaluate the efficacy and safety of GB221. |
| C max | Up to 5 weeks | C max |
| AUC (0- t) | Up to 5 weeks | AUC (0- t) |
| AUC (0- ∞ ) | Up to 5 weeks | AUC (0- ∞ ) |
| T max | Up to 5 weeks | T max |
| V/F | Up to 5 weeks | V/F |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Antidrug antibody, ADA | Up to 5 weeks | Antidrug antibody, ADA |
Countries
China
Contacts
Primary ContactShawn Yu, Master
Outcome results
None listed