Clinical trial NCT04189211: A Clinical Trial of BAT8001 on Safety, Tolerability and Pharmacokinetics for Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: HER2-Positive Solid Tumors
Lead sponsor: Bio-Thera Solutions
Sponsor class: INDUSTRY
First posted: 2019-12-06
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Patients with advanced solid tumors refractory to standard treatment or of intolerable or no standard treatment.
2. Patients with breast cancer or gastric cancer (including gastroesophageal junction adenocarcinoma) histopathologically or cytologically diagnosed and tested HER2-positive (IHC 3+ and/or ISH+);
3. At least one measurable lesion according to RECIST version 1.1;
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
5. Absence of severe hematopoietic abnormalities, and basically normal heart, lung, liver and kidney functions;
6. Expected survival ≥ 3 months;
7. Left ventricular ejection fraction (LVEF) by ultrasound examinations higher than the lower limit of normal range defined by the study site;
8. 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:

1. Have active hepatitis B virus or hepatitis C;
2. Patients who are positive for the human immunodeficiency virus;
3. Patients with a history of immunodeficiency, including HIV-positive or other acquired or congenital immunodeficiencies, or a history of organ transplantation;
4. Patients with clinically significant active infection as determined by the investigator;
5. Other concurrent, severe or uncontrollable systemic diseases (such as clinically significant metabolic disorders, poor wound healing, ulcers, etc.);
6. 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;
7. 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;
8. 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;
9. Grade ≥ 2 peripheral neuropathy ;

Primary outcomes:
measure: Dose-limiting toxicity（DLT）
timeFrame: A minimum of 21 days after first dose of BAT8001
measure: Maximum tolerated dosed (MTD)
timeFrame: A minimum of 21 days after first dose of BAT8001
measure: Area under the curve (AUC)-BAT8001(antibody-drug conjugate), total antibody and Batansine (a maytansine derivative, which is the 3AA-MDC complex)
timeFrame: 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
measure: Maximum serum drug concentration (Cmax)-BAT8001(antibody-drug conjugate), total antibody and Batansine (a maytansine derivative, which is the 3AA-MDC complex)
timeFrame: 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
measure: Half-life period(t1/2)
timeFrame: 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
measure: Anti drug antibodies (ADA)
timeFrame: pre-infusion (Hour 0) on Day 1 of Cycle 1, 2, 3, 4 (each cycle is 21 days) up to approximately 3 months
measure: Neutralizing anti-drug antibodies (NADA)
timeFrame: pre-infusion (Hour 0) on Day 1 of Cycle 1, 2, 3, 4 (each cycle is 21 days) up to approximately 3 months
Secondary outcomes:
measure: Progression free survival time(PFS)
timeFrame: Baseline to the end of the study (up to 3 years)
measure: Overall response rate(ORR)
timeFrame: Baseline to the end of the study (up to 3 years)
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Shusen Wang, M.D.
role: PRINCIPAL_INVESTIGATOR
References: