Clinical trial NCT05848466: Assessment of Safety, Tolerability and Pharmacokinetics With BAT8010 for Injection in Advanced Malignant Solid Tumors Patients
Official title: A Phase 1, Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of BAT8010 for Injection in Patients With Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced or Metastatic Solid Tumors
Lead sponsor: Bio-Thera Solutions
Sponsor class: INDUSTRY
First posted: 2023-05-08
Enrollment: 109
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The goal of this interventional study is to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of BAT8010 for injection in patients with advanced or metastatic solid tumors, explore the maximum tolerable dose. Participants will be given one of below dose once every three weeks: 0.8mg/kg, 1.2mg/kg, 2.4mg/kg, 3.6mg/kg, 4.8mg/kg, 6.0mg/kg, 7.2mg/kg, 8.4mg/kg. The dose escalation follow adopt accelerated titration and "3+3" dose increasing rule.


Eligibility criteria: Inclusion Criteria:

* Voluntary signing of informed consent.
* The expected survival period is more than 3 months base on the evaluation of the investigator.
* Eastern Cooperative Oncology Group (ECOG) should be 0-1.
* Patients who fail to standard treatment or have no standard treatment or are not suitable for standard treatment at this stage, and who have Human epidermal growth factor receptor-2 (HER2) expression (including Immunohistochemistry (IHC)3+, IHC2+/fluorescence in situ hybridization (FISH)+and IHC2+/FISH - patients) confirmed by histopathology and cytopathology, the dose escalation stage includes but is not limited to breast cancer, gastric cancer, non-small cell lung cancer, biliary tract cancer, colorectal cancer, urothelial cancer, etc., and the expansion stage only includes breast cancer.
* An evaluable tumor focus was necessary in the dose escalation stage, and at least one measurable tumor focus in the dose expanding stage (according to RECIST 1.1 standard).
* Enough organs, bone marrow reserve function and heart function.
* Must agree to take effective contraceptive methods to prevent pregnancy.

Exclusion Criteria:

* Previously received HER2 targeted drug therapy such as trastuzumab or pertuzumab, Trastuzumab Emtansine or Enhertu, and the treatment of topoisomerase I inhibitors (such as irinotecan), there were adverse event (AE) equal to or pass 3 levels that were determined to be treatment-related or drug related
* Before the first administration of the investigational drug, the AE (CTCAE5.0) caused by previous anti-tumor treatment was still higher than grade 1
* Primary central nervous system tumor or symptomatic central nervous system metastasis, meningeal metastasis or previous history of epilepsy. Patients with asymptomatic or symptomatic central nervous system metastasis who have achieved clinical control but are judged stable by the investigator can be included.
* Major surgery has been performed within 28 days before the first use of the study drug, or if it has been more than 21 days after surgery, but the postoperative complications are still continuing.
* Subjects who had severe infection within 4 weeks before the first administration, or had any symptoms and signs of active infection within 2 weeks before the first administration.
* Untreated or under treatment tuberculosis subjects, with a history of immune deficiency, or other immune deficiency diseases, or with a history of organ transplantation.
* Active hepatitis B virus infected, hepatitis C virus infected, Treponema pallidum antibody positive and Rapid plasma reagin ring card test (RPR) positive.
* Patients with symptomatic congestive heart failure (New York Heart Association (NYHA) grade II to IV) or serious arrhythmia requiring treatment (QTc prolongation of 12-lead electrocardiogram (ECG) 450 ms \[male\], 470 ms \[female\]), and patients with myocardial infarction and unstable angina pectoris in the past 6 months. Except for atrial fibrillation or paroxysmal supraventricular tachycardia
* Patients who have a history of non-infectious pneumonia requiring glucocorticoid treatment or who currently have interstitial lung disease.
* There are any other serious potential diseases.
* Previous anti-tumor therapy (such as chemotherapy, endocrine therapy, targeted therapy, immunotherapy or tumor embolization) is less than 28 days from the first study administration.
* Therapeutic radiopharmaceuticals must be discontinued 8 weeks before the first study administration.
* Known allergy or intolerance to the study drug or its excipients.
* Pregnant or lactating women.
* The study participants who were considered unsuitable for the study by investigator.

Primary outcomes:
measure: Dose-limiting toxicity (DLT)
timeFrame: 3 weeks
measure: maximum tolerated dose (MTD)
timeFrame: 3 weeks
Secondary outcomes:
measure: Pharmacokinetic
timeFrame: every cycle until 18 weeks (one cycle equals 3 weeks)]
measure: Immunogenicity
timeFrame: every cycle until 18 weeks, every 4 cycles after 18 weeks (one cycle equals 3 weeks), up to 1 year
measure: Objective response rate (ORR)
timeFrame: through study completion, an average of 2 years
measure: Duration of remission (DoR)
timeFrame: Through study completion, an average of 2 years
measure: Disease Control Rate (DCR)
timeFrame: through study completion, an average of 2 years
measure: Progression free survival (PFS)
timeFrame: through study completion, an average of 2 years
measure: Total survival period (OS)
timeFrame: through study completion, an average of 2 years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
affiliation: Bio-Thera Solutions
name: Chaohe Wang
role: STUDY_DIRECTOR
References: