Trial Title:
To Evaluate the Safety, Tolerance and Pharmacokinetics of BAT8007 for Injection in Patients With Advanced Solid Tumors
NCT ID:
NCT05879627
Condition:
Advanced Solid Tumors
Conditions: Official terms:
Neoplasms
Exatecan
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Intervention:
Intervention type:
Drug
Intervention name:
BAT8007 for injection
Description:
Intravenous infusion: once every three weeks.The infusion time in the first cycle is
recommended to be ≥ 90 minutes. If no infusion reaction occurs, the subsequent cycle can
be completed within 30~120 minutes.
Arm group label:
Cohort 1
Arm group label:
Cohort 2
Arm group label:
Cohort 3
Arm group label:
Cohort 4
Arm group label:
Cohort 5
Arm group label:
Cohort 6
Arm group label:
Cohort 7
Arm group label:
Cohort 8
Other name:
Recombinant all human anti Nectin-4 monoclonal antibody for injection Exatecan conjugate
Summary:
A multicenter, open phase I clinical study to evaluate the safety, tolerance and
pharmacokinetics of BAT8007 for injection in patients with advanced solid tumors.
Detailed description:
This is a multicenter, open, dose increasing and dose expanding Phase I clinical study.
About 169~292 patients will be enrolled from research centers in China, the United
States, Australia, etc. In the dose increasing stage, accelerated titration and "3+3"
dose increasing design were used to explore the safety, tolerance and PK characteristics
of BAT8007 for injection in patients with advanced solid tumors. During the dose
increasing test, select the appropriate dose according to the previous study data for the
extended study.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 18 to 75 years old (including the boundary value), regardless of gender;
- Sign the informed consent form voluntarily;
- Dose-climbing studies: cytologically or histologically confirmed patients with
advanced solid tumors who failed standard therapy, had no standard therapy, were
intolerant to standard therapy, or refused to receive standard therapy;
Dose-expansion studies: Patients with cytologically or histologically confirmed
locally advanced/metastatic urothelial carcinoma or other advanced or metastatic
solid tumors with cytologically or histologically confirmed failure of standard
therapy or intolerance to standard therapy (at least first-line systemic antitumor
therapy).
- Patients in the dose increasing study must have an evaluable tumor focus, and
patients in the dose expanding study must have at least one measurable tumor focus
(according to RECIST 1.1 standard);
- The physical status score of the East American Cooperative Oncology Group (ECOG) is
required to be 0 or 1;
- The investigator assessed that the expected survival period was ≥ 12 weeks;
- Prepare sufficient organ and bone marrow reserve function, and the definition is as
follows: blood routine test (no blood component, cell growth factor support
treatment and no drug to correct the number of blood cells within 14 days before the
first administration), absolute neutrophil count (ANC) ≥ 1.5 × 109/L platelet count
≥ 90 × 109/L hemoglobin ≥ 90g/L coagulation function: International normalized ratio
(INR) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN (those not
receiving anticoagulation therapy) can be included in patients receiving oral
anticoagulation therapy with INR of 2-3; Subjects currently receiving intravenous or
subcutaneous anticoagulation therapy must be excluded. Liver function: total
bilirubin (TBIL) generally ≤ 1.5 × ULN； Hepatocellular carcinoma, liver metastasis ≤
2 × ULN alanine aminotransferase (ALT), aspartate aminotransferase (AST) generally ≤
2.5 × ULN； Hepatocellular carcinoma, liver metastasis ≤ 5 × ULN Renal function:
serum creatinine ≤ 1.5 × ULN or serum creatinine clearance>60ml/min (Cockcroft Gault
formula is adopted, see appendix)
- Female patients with fertility must have negative serum pregnancy test within 7 days
before the first administration and be willing to take effective birth
control/contraception methods to prevent pregnancy during the study period until 6
months after the last administration. Male patients must agree to take effective
contraceptive methods during the study period until 6 months after the last
administration of the drug; Postmenopausal women must be amenorrhoea for at least 12
months before they are considered infertile;
- We must agree to abide by the epidemic prevention regulations of the host country
and region against COVID-19 novel coronavirus, and minimize the exposure to COVID-19
from the screening period to the end of the study (28 days of safety follow-up);
- Able to understand the test requirements, willing and able to follow the test and
follow-up procedures.
Exclusion Criteria:
- Within 4 weeks before the first administration of the study drug, he received
experimental drug treatment;
- Subjects who have received previous treatment with Nectin-4 or related target
research drugs (not limited to antibody, ADC, etc.);
- Have received chemotherapy, radiotherapy, biological therapy, endocrine therapy,
immunotherapy and other anti-tumor treatments within 4 weeks before the first use of
the study drug, except for the following: ① Nitrosourea or mitomycin C within 6
weeks before the first use of the study drug; ② Oral fluorouracil and small molecule
targeted drugs were taken 2 weeks before the first use of the study drug or within 5
half lives of the drug (whichever is longer); ③ Within 2 weeks before the first use
of the investigational drug, the systematic treatment of traditional Chinese
medicine/Chinese patent medicine with clear anti-tumor effect and drugs with
immunomodulatory effect (including but not limited to thymosin, interferon,
interleukin, etc.); ④ Palliative radiotherapy was performed within 2 weeks before
the first use of the study drug;
- After receiving any topoisomerase I inhibitor (such as irinotecan) in the past,
there has been a drug related or unknown AE ≥ 3 levels (using CTCAE version 5.0 for
grading);
- Before the first administration of the study drug, AE (CTCAE version 5.0) caused by
previous anti-tumor treatment was still greater than grade 1, except for the
following circumstances: a. alopecia; B pigmentation; c. The distal neurotoxicity
caused by chemotherapy and radiotherapy can not be further recovered after judgment;
d. Stable hypothyroidism after hormone replacement therapy;
- Patients who have undergone major surgery or have not recovered from surgery within
4 weeks before the first administration of the study drug, or have experienced
significant trauma, or need to undergo elective surgery during the trial. Note:
Those who have undergone minor surgery ≥ 28 days before screening must have fully
recovered from the surgery before the first administration, except for the
indwelling operation at the intravenous infusion port;
- Have a history of allograft cell or solid organ transplantation;
- Primary central nervous system tumor or symptomatic central nervous system
metastasis (meningeal metastasis with or without symptoms must be excluded).
Patients with asymptomatic or symptomatic central nervous system metastasis who have
reached clinical control but are judged by the researcher to be stable can be
included, but the following conditions must be met simultaneously: a The clinical
symptoms were stable ≥ 4 weeks before the first administration; b. No evidence of
progression of central nervous system disease was found in brain MRI enhancement
within 4 weeks before the first administration; c. The antiepileptic drugs have been
stopped at least 2 weeks before the first medication;
- In the dose expansion study, there were other active malignant tumors within 3 years
before the first administration. Except for locally cured tumors (such as skin basal
cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer or breast
cancer in situ);
- The following cardiovascular diseases occurred within 6 months before the first drug
use: symptomatic heart failure with NYHA grade of 2 or above, left ventricular
ejection fraction (LVEF)<50%, unstable arrhythmia or unstable angina pectoris,
myocardial infarction requiring treatment, pulmonary embolism Uncontrolled
hypertension (this protocol is defined as systolic blood pressure > 160mmHg and/or
diastolic blood pressure > 100mmHg after treatment, although the optimal
antihypertensive treatment is used, and it is evaluated by the researcher as
clinically significant). Note: 3 times of 12 lead ECG suggested that QTc interval
extension>450 ms (male) or>470 ms (female) should be excluded; The patients with
atrial fibrillation or paroxysmal supraventricular tachycardia that must be treated
can be considered to be included after the investigator has assessed that the
condition is stable;
- Suffering from any other disease, physical examination or laboratory examination
results, which are not suitable for the use of the study drug according to the
judgment of the investigator;
- Subjects who had previously suffered from non infectious pneumonia/pulmonary
inflammation requiring glucocorticoid treatment, or currently suffered from
interstitial lung disease (ILD), or failed to rule out ILD/pulmonary inflammation
through imaging examination during the screening period;
- Untreated or under treatment tuberculosis subjects, including but not limited to
tuberculosis; Those who have been treated with standardized anti tuberculosis
treatment and confirmed to be cured by researchers can be included;
- Serious infection occurred within 4 weeks or active infection occurred within 2
weeks before the first medication;
- People infected with the following diseases: human immunodeficiency virus (HIV)
infection; Active hepatitis B virus infected persons [hepatitis B surface antigen
(HBsAg) is positive, and the detection of hepatitis B virus deoxyribonucleic acid
(HBV-DNA) is>200 IU/ml or 103 copies/ml]; HCV infected persons [HCV antibody and
viral ribonucleic acid (HCV RNA) detection results are positive]; Treponema pallidum
antibody positive and RPR positive;
- Known hypersensitivity or delayed anaphylaxis to any component of the study drug;
- It is known that there has been ≥ grade 3 allergic reaction to macromolecular
protein preparation/monoclonal antibody;
- Patients with uncontrollable pleural effusion, pericardial effusion or peritoneal
effusion within 2 weeks before the first administration or who need drainage;
- Those with the following risk of thrombosis or bleeding:
1. Cerebrovascular accident or transient ischemic attack occurred within 6 months
before the first administration;
2. There is a history of deep vein thrombosis, pulmonary embolism or any other
serious thromboembolism within 3 months before the first administration
(implanted venous infusion port or catheter derived thrombosis, or superficial
venous thrombosis is not considered as "serious" thromboembolism);
3. Any life threatening bleeding event or grade 3 or 4 gastrointestinal/variceal
bleeding event requiring blood transfusion, endoscopy or surgery within 3
months before the first administration;
4. Other diseases that the researchers believe have a high risk of bleeding or
thrombosis in the future;
- Existence of any other serious underlying disease (such as Gilbert syndrome,
unstably controlled diabetes, active gastric ulcer, unstably controlled convulsion,
coagulation dysfunction with serious symptoms or signs);
- Known psychiatric diseases, drug abuse history, alcohol abuse history or drug abuse
history, which affect the test results;
- Pregnant or lactating women or women or men preparing for childbirth;
- Those who have received any live attenuated vaccine within 4 weeks before the first
administration of the study drug. About COVID-19 vaccination: the interval between
COVID-19 vaccination and the first administration must be at least 14 days, and
COVID-19 vaccination is not allowed during DLT observation. Some special cases can
be included in the study with the consent of the medical supervisor;
- It is estimated that the patient's compliance to participate in this clinical study
is insufficient or the investigator believes that there are other factors that are
not suitable for participating in this study.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Sun Yat-sen University Cancer Center
Address:
City:
Guangzhou
Country:
China
Status:
Recruiting
Contact:
Last name:
Fangjian Zhou
Contact backup:
Last name:
Su Li
Start date:
January 17, 2023
Completion date:
July 1, 2025
Lead sponsor:
Agency:
Bio-Thera Solutions
Agency class:
Industry
Collaborator:
Agency:
Zhejiang Tumor Hospital
Agency class:
Other
Source:
Bio-Thera Solutions
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05879627
