Clinical Study of Recombinant Anti-HER2 Humanized Monoclonal Antibody for Injection

A Randomized, Multicenter, Phase I/IIa Clinical Study to Evaluate the Tolerability, Safety, Efficacy, Pharmacokinetics and Immunogenicity of GB221 for Injection for the Treatment of HER2-positive Breast Cancer Patients

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.

Study Overview

• Status: Recruiting
• Conditions: HER2-positive Breast Cancer
• Intervention / Treatment: Biological: GB221,2 mg/kg; Biological: GB221,6 mg/kg; Biological: Herceptin,6 mg/kg; Biological: GB221,8mg/kg; Biological: GB221:2mg/kg and Capecitabi:1000mg/kg; Biological: Herceptin:2mg/kg and Capecitabin:1000mg/kg

• Study Type: Interventional
• Enrollment (Anticipated): 132
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100071
      • Recruiting
      • Affiliated Hospital of Academy of Military Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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/exclusion criteria can be enrolled);

5. There is at least one measurable target lesion (based on RECIST 1.1 criteria):

   • According to Response Evaluation Criteria in Solid Tumors (RECIST V1.1), the target lesions must be accurately measured in at least one dimension (refer to appendix 5);
   • No radiotherapy for target lesions;
6. The investigators consider that the subject has recovered from the toxic reactions caused by the previous chemotherapy 4 weeks after the last chemotherapy (subjects who are receiving Xeloda monotherapy and achieve efficacy or stable disease can be enrolled in this study).
7. The expected survival is 3 months or longer;
8. ECOG performance status is 0, 1 or 2;
9. The left ventricular ejection fraction (LVEF)≥50%;

10. 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; if there is any hepatic metastasis, ALT and AST ≤5×ULN;
    • Serum Cr ≤ULN;
11. Normal coagulation function test;
12. 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 with known or suspected brain metastasis: Subjects with evidence indicating signs or symptoms of brain metastasis are not allowed to participate in this study unless such brain metastasis is excluded by CT or MRI. However, subjects whose brain metastasis lesions have been controlled can be enrolled (no progression within at least 4 weeks after radiotherapy and/or no neurological symptom or sign after surgical resection, treatment with dexamethasone or mannitol is not necessary);
3. Subjects who had disease progression after previous chemotherapy with Xeloda.

4. 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;
5. Uncontrolled hypertension (defined as screening systolic blood pressure ≥ 180mmHg and/or diastolic blood pressure ≥110mmHg);
6. Known HIV, HBV or HCV infection;
7. Allergic constitution; known allergic to the components of the investigational product;
8. Have drug abuse history or alcohol addiction history;
9. Participated in other clinical studies within 4 weeks before the initiation of the study;
10. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: GB221,2mg/kg; Coprelotamab Injection, 2 mg/kg, Single dose,	Biological: GB221,2 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; Other Names: Coprelotamab Injection
EXPERIMENTAL: GB221,6mg/kg; Coprelotamab Injection, 6 mg/kg, Single dose,	Biological: GB221,6 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; Other Names: Coprelotamab Injection
ACTIVE_COMPARATOR: Herceptin,6mg/kg; Trastuzumab Injection, 6 mg/kg, Single dose,	Biological: Herceptin,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; Other Names: Trastuzumab Injection
EXPERIMENTAL: GB221,8mg/kg; Coprelotamab Injection, 8 mg/kg, Single dose,	Biological: GB221,8mg/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; Other Names: Coprelotamab Injection
EXPERIMENTAL: GB221+ Capecitabine; Multiple dose groups	Biological: GB221:2mg/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.
ACTIVE_COMPARATOR: Herceptin+Capecitabine; Multiple dose groups	Biological: Herceptin: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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
maximum tolerated dose,MTD	To evaluate the efficacy and safety of GB221.	Up to 5 weeks
C max	C max	Up to 5 weeks
AUC (0- t)	AUC (0- t)	Up to 5 weeks
AUC (0- ∞ )	AUC (0- ∞ )	Up to 5 weeks
T max	T max	Up to 5 weeks
T 1/2	T 1/2	Up to 5 weeks
CL/F	CL/F	Up to 5 weeks
V/F	V/F	Up to 5 weeks
K e	K e	Up to 5 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antidrug antibody, ADA	Antidrug antibody, ADA	Up to 5 weeks

Collaborators and Investigators

• Sponsor: Genor Biopharma Co., Ltd.
• Investigators: Principal Investigator: Ze Fei Jiang, Ph.D, Affiliated Hospital of Academy of Military Medical Sciences

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 28, 2014
• Primary Completion (ANTICIPATED): December 1, 2021
• Study Completion (ANTICIPATED): December 1, 2022

Study Registration Dates

• First Submitted: November 12, 2019
• First Submitted That Met QC Criteria: November 19, 2019
• First Posted (ACTUAL): November 20, 2019

Study Record Updates

• Last Update Posted (ACTUAL): March 3, 2021
• Last Update Submitted That Met QC Criteria: March 2, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Trastuzumab
• Other Study ID Numbers: GENOR GB221-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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