Trial Title:
BAT7104 Injection in Patients With Advanced Malignant Tumors.
NCT ID:
NCT05767060
Condition:
Advanced Malignant Tumor
Conditions: Official terms:
Neoplasms
Antibodies, Bispecific
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:
BAT7104 injection
Description:
According to the protocol, each dose group is given intravenous infusion at the rate of
mg/kg, and the recommended infusion time is ≥ 60 minutes. Once every two weeks (Q2W), on
the first day of each cycle.
Arm group label:
BAT7104 Injection 0.1 mg/kg
Arm group label:
BAT7104 Injection 0.3 mg/kg
Arm group label:
BAT7104 Injection 1 mg/kg
Arm group label:
BAT7104 Injection 10 mg/kg
Arm group label:
BAT7104 Injection 20 mg/kg
Arm group label:
BAT7104 Injection 3 mg/kg
Arm group label:
BAT7104 Injection 40 mg/kg
Other name:
Recombinant anti-PD-L1/CD47 bispecific antibody injection
Summary:
A multi-center, open phase Ia/Ib clinical study to evaluate the safety, tolerance,
pharmacokinetics and preliminary clinical efficacy of BAT7104 injection in patients with
advanced malignant tumors.
Detailed description:
This is a multi-center, open, dose-increased and dose-expanded phase I clinical study.
About 18-42 patients will be recruited from research centers in China. In the stage of
dose increase, the safety, tolerance, pharmacokinetics and preliminary clinical efficacy
of BAT7104 injection in patients with advanced malignant tumors were investigated by
using accelerated titration and "3+3" dose increase design. During the dose increase
test, the appropriate dose was selected according to the previous study data of the
extended study.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Age: ≥ 18 years old and ≤ 80 years old, gender: male or female;
2. The investigator evaluated the expected survival period to be at least 3 months;
3. The requirement of the ECOG physical fitness score is 0 or 1;
4. Patients with advanced malignant tumors who have failed to receive standard
treatment, have no standard treatment, do not tolerate standard treatment or refuse
to accept standard treatment confirmed by cytology or pathology;
5. There must be an evaluable tumor focus in the dose increasing stage, and at least
one measurable tumor focus in the dose expanding stage (solid tumors refer to RECIST
1.1 standard, lymphoma refer to Lugano 2014 evaluation standard);
6. It has sufficient organ and bone marrow reserve function, which is defined as
follows:
System laboratory reference value:
Blood routine (no blood transfusion, no use of hematopoietic stimulating factor and
no use of drugs to correct blood cell count within 14 days before the first
administration):
Absolute neutrophil count ≥ 1.5 x 109/L;Platelet count ≥ 90 x109/L;Hemoglobin ≥
90g/L;
Coagulation function:
International standardized ratio (INR) and activated partial thromboplastin time
(APTT) ≤ 1.5xULN (without anticoagulant treatment), those who receive oral
anticoagulant treatment and whose INR is 2~3 can be included.
Liver function:
Total bilirubin (TBIL) ≤ 1.5xULN;Hepatocellular carcinoma, Gilbert's syndrome, liver
metastasis ≤ 2xULN;Alanine aminotransferase (ALT), aspartate aminotransferase (AST)
≤ 2.5xULN;Hepatocellular carcinoma, liver metastasis ≤ 5xULN renal function Serum
creatinine or Serum creatinine clearance ≤ 1.5xULN or>50ml/min (using
Cockcroft-Gault formula, see appendix)
7. Agree to provide archived pathological tissue or fresh biopsy tumor tissue for the
detection of PD-L1, CD47 expression level or receptor occupancy and other
pharmacodynamic indicators (not as a necessary inclusion standard); Female patients
with fertility must have negative serum pregnancy test within 7 days before the
first administration and are willing to take effective birth control/contraception
methods to prevent pregnancy during the study period until 6 months after the last
administration of the study. Male patients must agree to take effective
contraceptive methods during the study period and within 6 months after the last
administration of the study; Postmenopausal women must have amenorrhea for at least
12 months before they are considered infertile.
Exclusion Criteria:
1. Have received any anti-CD47 antibody and SIRP within 4 weeks before the first
administration α Antibodies or CD47/SIRP α Recombinant protein therapy;
2. He has received chemotherapy, radiotherapy, biological therapy, endocrine therapy,
immunotherapy and other anti-tumor treatment within 4 weeks before the first use of
the study drug, with the exception of 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 are 2 weeks before the first use of the study drug or
within 5 half-lives of the drug (whichever is longer); ③ The systematic treatment of
traditional Chinese medicine/proprietary Chinese medicine with clear anti-tumor
effect and drugs with immunomodulatory effect (including but not limited to
thymosin, interferon, interleukin, etc.) is within 2 weeks before the first use of
the study drug;
3. Those who are participating in or have participated in the experimental drug or
medical device intervention clinical research within 4 weeks before the first
administration of this study cannot be included; In the survival follow-up stage of
the intervention study, if the time between the first administration and the end of
the previous study (the last administration) meets the above exclusion criteria, it
can be included;
4. Inoculated or planned to receive live/attenuated vaccine and mRNA vaccine within 4
weeks before screening;
5. Pregnant or lactating women;
6. AEs caused by previous anti-tumor therapy are still higher than grade 1 (based on
CTCAE v5.0) before the first administration of the study drug (except for AEs such
as hair loss and fatigue that cannot be restored to ≤ grade 1 and will remain stable
for a long time according to the judgment of the researcher based on clinical actual
conditions, except for grade 2 peripheral neurotoxicity, and hypothyroidism
stabilized by hormone replacement therapy);
7. Those who have had ≥ 3 levels of irAE in the past or have terminated immunotherapy
due to any level of irAE;
8. Primary central nervous system tumor, central nervous system metastasis with related
symptoms, meningeal metastasis or previous history of epilepsy should be excluded.
Patients with asymptomatic or asymptomatic central nervous system metastasis who
have been clinically controlled but have been judged stable by the researcher can be
included, but the following conditions must be met at the same time: a The disease
was stable ≥ 4 weeks before the first administration; B. No evidence of central
nervous system disease progression was found in MRI enhancement of the head within 4
weeks before the first administration; C. The anticonvulsant drugs have been stopped
at least 2 weeks before the first administration, and the dosage of prednisone is ≤
10mg/day or equivalent dose of hormone;
9. Patients who have undergone major organ surgery (excluding puncture biopsy) or had
significant trauma within 4 weeks before the first use of the study drug, or who
need to undergo elective surgery during the trial period;
10. Have a history of tissue or organ transplantation;
11. Patients with severe infection within 4 weeks before the first medication, including
but not limited to infection complications, bacteremia, severe pneumonia, etc.
requiring hospitalization; Patients with active infection before the first
administration were excluded;
12. Known history of human immunodeficiency virus (HIV) infection;
13. Active hepatitis B, untreated chronic hepatitis B or treated but uncontrolled
chronic hepatitis B (HBV DNA>200 IU/mL or>103 copies/ml);
14. Active HCV infected patients (HCV antibody positive and HCV-RNA level higher than
the lower limit of detection);
15. Untreated or under treatment tuberculosis patients, including but not limited to
tuberculosis; Those who have received standard anti-tuberculosis treatment and have
been confirmed as cured by researchers can be included;
16. Known to have a history of severe allergy, or known to have had ≥ grade 3 allergic
reaction to macromolecular protein preparation/monoclonal antibody, and any
component of test drug;
17. Patients with active, or had a history of autoimmune diseases that may recur
(excluding vitiligo, autoimmune thyroid diseases that can be treated with hormone
replacement therapy, and type 1 diabetes patients);
18. Have received systemic glucocorticoid (prednisone>10mg/day or equivalent dose of the
same drug) or other immunosuppressive treatment within 14 days before the first use
of the study drug, except for the following cases: ① use of local, ocular,
intraarticular, intranasal and inhaled glucocorticoid treatment, ② short-term use of
glucocorticoid for preventive treatment (such as prevention of contrast agent
allergy);
19. Patients who have a history of non-infectious pneumonia requiring glucocorticoid
treatment or who currently have interstitial lung disease within 1 year before the
first administration;
20. There is a history of serious cardio-cerebrovascular disease, including but not
limited to: ① heart failure or left ventricular ejection fraction (LVEF)<50% with
NYHA grade II or above; ② There are serious cardiac rhythm or conduction
abnormalities, such as ventricular arrhythmia requiring clinical intervention, Ⅱ - Ⅲ
degree atrioventricular block, etc.; ③ Acute coronary syndrome, congestive heart
failure, aortic dissection, stroke or other cardiovascular and cerebrovascular
events of grade 3 or above occurred within 6 months before the first administration;
④ Hypertension that cannot be controlled clinically (this protocol is defined as
that although antihypertensive treatment is adopted, the systolic blood pressure is
more than 150 mmHg and/or diastolic blood pressure is more than 100 mmHg after
treatment, and has clinical significance after evaluation by the researcher);
21. Those with the following risk of thrombosis or bleeding:
A. Myocardial infarction, unstable angina pectoris, cerebrovascular accident or
transient ischemic attack occurred within 6 months before the first administration;
B. There is a history of deep venous thrombosis, pulmonary embolism or any other
serious thromboembolism within 3 months before the first administration (implantable
venous infusion port or catheter-derived thrombosis, or superficial venous
thrombosis is not considered as "serious" thromboembolism); C. Any life-threatening
bleeding event or grade 3 or 4 gastrointestinal/variceal bleeding event requiring
blood transfusion, endoscopy or surgical treatment within 3 months before the first
administration; D. Other diseases that the researcher believes have a high risk of
bleeding or thrombosis in the future;
22. Patients who are known to have a history of abuse or drug abuse of psychotropic
substances and are considered to affect the compliance of this study;
23. Have a history of hemolytic anemia or Evans syndrome in the past 3 months;
24. In addition to the tumors at the time of study, there are other active malignant
tumors within 3 years before the first administration (not excluding locally cured
tumors, such as skin basal cell carcinoma, superficial bladder cancer cancer or
breast cancer in situ);
25. Patients with pleural effusion, pericardial effusion or ascites that are not
controlled or need drainage;
26. Patients who are not suitable for this study according to the researcher.
Gender:
All
Minimum age:
18 Years
Maximum age:
80 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Li Zhang
Address:
City:
Guangzhou
Country:
China
Status:
Recruiting
Contact:
Last name:
Li Zhang
Phone:
13902282893
Start date:
January 20, 2022
Completion date:
January 20, 2024
Lead sponsor:
Agency:
Bio-Thera Solutions
Agency class:
Industry
Collaborator:
Agency:
Sun Yat-sen University
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/NCT05767060
