Advanced Malignant Tumor
Conditions
Brief 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.
Interventions
DRUGBAT7104 injection
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.
Sponsors
Sun Yat-sen University
Bio-Thera Solutions
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose limiting toxicity (DLT), | A minimum of 28 days after first dose of BAT-7104 | umber of subjects who experience DLT events during 28 days. Toxicity will be graded according to CTCAE, Version 5.0. |
| Adverse Events (AEs) | AE needs continuous monitoring and evaluation from the first administration to 90 days after the last administration or before receiving new anti-tumor treatment. | Incidence of treatment -related AEs as assessed by CTCAE, Version 5.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | 12 months (anticipated) | The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR, based on RECIST Version 1.1. |
| Tmax (Time to reach maximum serum concentration) | up to Cycle 6, each cycle is 14 days | Time to Maximum concentration |
| AUC0-inf after Cycle 1 administration and AUC0- λ after Cycle 6 administration | up to Cycle 6, each cycle is 14 days | — |
| Cmax, | up to Cycle 6, each cycle is 14 days | Maximum observed plasma or serum concentration |
| Vss (volume of distribution at steady state) | up to Cycle 6, each cycle is 14 days | Amount of drug in the body divided by plasma concentration |
| t1/2 (terminal half-life) | up to Cycle 6, each cycle is 14 days | Apparent terminal-phase disposition half-life. |
| Systemic Clearance (CL) | up to Cycle 6, each cycle is 14 days | Systemic dose clearance |
| Anti-drug antibodies (ADA) and neutralizing antibodies (NAb) | up to Cycle 6, each cycle is 14 days | — |
Countries
China
Outcome results
None listed