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

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

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)。

Study Overview

• Status: Unknown
• Conditions: HER2-Positive Solid Tumors
• Intervention / Treatment: Drug: BAT8001

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.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat-sen University Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 ;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Bio-Thera Solutions

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 7, 2017
• Primary Completion (ANTICIPATED): December 31, 2019
• Study Completion (ANTICIPATED): December 31, 2020

Study Registration Dates

• First Submitted: November 26, 2019
• First Submitted That Met QC Criteria: December 5, 2019
• First Posted (ACTUAL): December 6, 2019

Study Record Updates

• Last Update Posted (ACTUAL): December 6, 2019
• Last Update Submitted That Met QC Criteria: December 5, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Trastuzumab; Maytansine
• Other Study ID Numbers: BAT-8001-001-CR

Drug and device information, study documents

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