A Clinical Trial of BAT8001 on Safety, Tolerability and Pharmacokinetics for Patients

Study Overview
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Brief Summary
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An Open-Label, Dose Escalation Phase I Clinical Trial on Safety, Tolerability and Pharmacokinetics of BAT8001 for Injection in Patients with HER2-Positive Solid Tumors (breast cancer or gastric cancer)。

Detailed Description
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This is an open-label, dose escalation Phase I clinical study in two stages. Stage 1 consists of the first four cycles where the tolerability, safety, pharmacokinetics and immunogenicity of BAT8001 for injections will be studied and preliminary efficacy will be evaluated. Efficacy and safety assessments continue from the fifth cycle until disease progression or intolerable toxicities.

Official Title
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An Open-Label, Dose Escalation Phase I Clinical Trial on Safety, Tolerability and Pharmacokinetics of BAT8001 for Injection in Patients With HER2-Positive Solid Tumors

Conditions
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HER2-Positive Solid Tumors

Intervention / Treatment
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* Drug: BAT8001


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with advanced solid tumors refractory to standard treatment or of intolerable or no standard treatment. Patients with breast cancer or gastric cancer (including gastroesophageal junction adenocarcinoma) histopathologically or cytologically diagnosed and tested HER2-positive (IHC 3+ and/or ISH+); At least one measurable lesion according to RECIST version 1.1; Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; Absence of severe hematopoietic abnormalities, and basically normal heart, lung, liver and kidney functions; Expected survival ≥ 3 months; Left ventricular ejection fraction (LVEF) by ultrasound examinations higher than the lower limit of normal range defined by the study site; The cumulative dose of anthracyclines should meet the following: the cumulative dose must not exceed the equivalent dose of 360 mg/m2 doxorubicin. Exclusion Criteria: Have active hepatitis B virus or hepatitis C; Patients who are positive for the human immunodeficiency virus; Patients with a history of immunodeficiency, including HIV-positive or other acquired or congenital immunodeficiencies, or a history of organ transplantation; Patients with clinically significant active infection as determined by the investigator; Other concurrent, severe or uncontrollable systemic diseases (such as clinically significant metabolic disorders, poor wound healing, ulcers, etc.); Moderate or severe dyspnea at rest caused by advanced malignant tumors or complications or serious primary lung diseases, or currently requiring continuous oxygen therapy, or currently having interstitial lung disease or pneumonia; Cardiac insufficiency within the past 6 months before enrollment based on the following definitions: Grade ≥ 3 symptomatic congestive heart failure (CHF) according to CTCAE v4.03, or a history of Grade ≥ 2 symptomatic congestive heart failure, transmural myocardial infarction, unstable angina according to New York Heart Association (NYHA) Functional Classification, or severe arrhythmia without proper medicinal control, severe heart block, uncontrolled hypertension, or clinically significant cardiovascular disease; Patients with central nervous system or brain metastasis symptoms, or who have received treatment for central nervous system or brain metastasis within 3 month before the first dose; Grade ≥ 2 peripheral neuropathy ;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1.2mg/kg of BAT8001<br>BAT8001 100mg/box, 1.2mg/kg IV infusions | Drug: BAT8001<br>* IV infusions.<br>* Other names: Recombinant Humanized Anti-HER2 Monoclonal Antibody-Maytansine Conjugate for Injection;|
| Experimental: 2.4mg/kg of BAT8001<br>BAT8001 100mg/box, 2.4mg/kg IV infusions | Drug: BAT8001<br>* IV infusions.<br>* Other names: Recombinant Humanized Anti-HER2 Monoclonal Antibody-Maytansine Conjugate for Injection;|
| Experimental: 3.6mg/kg of BAT8001<br>BAT8001 100mg/box, 3.6mg/kg IV infusions | Drug: BAT8001<br>* IV infusions.<br>* Other names: Recombinant Humanized Anti-HER2 Monoclonal Antibody-Maytansine Conjugate for Injection;|
| Experimental: 4.8mg/kg of BAT8001<br>BAT8001 100mg/box, 4.8mg/kg IV infusions | Drug: BAT8001<br>* IV infusions.<br>* Other names: Recombinant Humanized Anti-HER2 Monoclonal Antibody-Maytansine Conjugate for Injection;|
| Experimental: 6.0mg/kg of BAT8001<br>BAT8001 100mg/box, 6.0mg/kg IV infusions | Drug: BAT8001<br>* IV infusions.<br>* Other names: Recombinant Humanized Anti-HER2 Monoclonal Antibody-Maytansine Conjugate for Injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity（DLT） | DLT is defined as one of the following as per investigator related to study drug: Grade ≥ 3 non-hematologic, and non-liver organ toxicities (except for Grade 3 diarrhea, nausea and vomiting in the absence of prophylactics); Grade ≥ 3 cardiotoxicity, new segmental wall-motion abnormalities, or troponin I ≥ 0.2 ng/mL; Left ventricular ejection fraction (LVEF) ≤ 45% and a ≥ 10% decrease from baseline; Grade ≥ 4 thrombocytopenia or anemia; Grade ≥ 4 t neutropenia that persists for more than 4 days or accompanied by fever > 38.3 °C or persistent fever ≥ 38 °C for more than 1 hour; Grade ≥ 3 elevation in any one of total bilirubin (TBIL), aspartate transaminase (AST) or alanine transaminase (ALT). Serum transaminase > 3 × ULN and TBIL > 2 × ULN; For Grade 2 abnormalities in AST or ALT at baseline, a measurement ≥ 10 × ULN. | A minimum of 21 days after first dose of BAT8001 | 
| Maximum tolerated dosed (MTD) | The highest dose level resulting in a DLT in ≤ 1 of 6 patients was declared the MTD. | A minimum of 21 days after first dose of BAT8001 | 
| Area under the curve (AUC)-BAT8001(antibody-drug conjugate), total antibody and Batansine (a maytansine derivative, which is the 3AA-MDC complex) | AUC will be evaluated and reported for BAT8001 and its metabolites. | pre-infusion (Hour 0), 30 minutes after end of BAT8001 infusion on Day 1 Cycle 1, 2, 3, 4 (each cycle is 21 days) up to approximately 3 months | 
| Maximum serum drug concentration (Cmax)-BAT8001(antibody-drug conjugate), total antibody and Batansine (a maytansine derivative, which is the 3AA-MDC complex) | Maximum serum concentration (Cmax) immediately after dosing will be evaluated and reported for BAT8001 and its metabolites. | pre-infusion (Hour 0), 30 minutes after end of BAT8001 infusion on Day 1 Cycle 1, 2, 3, 4 (each cycle is 21 days) up to approximately 3 months | 
| Half-life period(t1/2) | Half-life (t1/2) will be evaluated and reported. | pre-infusion (Hour 0), 30 minutes after end of BAT8001 infusion on Day 1 Cycle 1, 2, 3, 4 (each cycle is 21 days) up to approximately 3 months | 
| Anti drug antibodies (ADA) | Plasma level of anti drug antibodies (ADA) correlated with BAT8001 plasma level | pre-infusion (Hour 0) on Day 1 of Cycle 1, 2, 3, 4 (each cycle is 21 days) up to approximately 3 months | 
| Neutralizing anti-drug antibodies (NADA) | Neutralizing anti-drug antibodies (NADA) correlated with BAT8001 | pre-infusion (Hour 0) on Day 1 of Cycle 1, 2, 3, 4 (each cycle is 21 days) up to approximately 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival time(PFS) | PFS is defined as the time from first dose date until the date of disease progression or death due to any reason, whichever occurs first. | Baseline to the end of the study (up to 3 years) | 
| Overall response rate(ORR) | determined by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. | Baseline to the end of the study (up to 3 years) |