Assessment of Safety and Preliminary Clinical Efficacy With BAT6005 in Advanced Malignant Solid Tumors

• Status: Not yet recruiting
• Trial end date: 2023-12-30
• Target enrollment: 0
• Participant gender: All

Summary

This research design for center, increasing openness, dose and dose extension phase I clinical trials, research the main evaluation BAT6005 injection single drug in patients with advanced malignant solid tumors in the safety, tolerability and PK characteristics, to explore the maximum tolerated dose and preliminary antitumor efficacy, provide the basis for subsequent clinical trials recommended dose.

Part I: single drug dose escalation study. Part TWO: dose extension study.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Bio-Thera Solutions

Criteria

Inclusion Criteria:

• Age: ≥18 years old, gender: male or female;

• The expected survival was assessed as at least 3 months;

• ECOG (Eastern Oncology Collaboration group) physical status score requirement: 0 or 1;

• Patients with locally advanced or metastatic malignant solid tumors confirmed by histology or cytology without standard therapy, failure of standard therapy, or inapplicable standard therapy;

• According to RECIST 1.1, there must be evaluable tumor focus in dose increase stage, and at least one measurable tumor focus in dose expansion stage;

• Sufficient organ and bone marrow reserve function is defined as follows:

System laboratory reference value Blood routine (no blood transfusion, no hematopoietic stimulator, and no medication to correct blood count within 14 days prior to initial administration) Neutrophil absolute count (ANC) ≥1.5×109 /L Platelet count ≥75×109/L Hemoglobin ≥85g/L Blood coagulation function Prothrombin time (PT) or International standardized ratio (INR) and activated partial thrombin time (APTT) ≤ 1.5×ULN (without anticoagulant therapy) Patients receiving oral anticoagulant therapy with INR of 2~3 could be included Liver function Total bilirubin (TBIL) -- ≤1.5×ULN Hepatocellular carcinoma, Gilbert's syndrome, liver metastasis ≤2×ULN Alanine aminotransferase (ALT), aspartate aminotransferase (AST) -- ≤2.5×ULN Hepatocellular carcinoma and liver metastasis ≤5×ULN renal function Serum creatinine clearance rate & GT; 50ml/min (Cockcroft-Gault formula, see appendix)

• Fertile women must have a negative serum pregnancy test within 7 days prior to the first dose and be willing to use an effective method of birth control/contraception to prevent pregnancy during the study period up to 6 months after the last dose.Male patients must agree to use an effective contraceptive method for the duration of the study until 6 months after the study's last dosing;Postmenopausal women must be amenorrhea for at least 12 months before they are considered infertile;

Exclusion Criteria:

• Prior treatment with anti-TiGit monoclonal antibody or anti-TiGit active double antibody;

• Had received chemotherapy, radiotherapy, biotherapy, endocrine therapy, immunotherapy and other anti-tumor treatments within 4 weeks prior to the first use of the study drug, except for the following:

1. Nitrosourea or mitomycin C within 6 weeks prior to initial use of the study drug;

2. Oral fluorouracil and small molecule targeted drugs should be administered 2 weeks prior to first use of the study drug or within 5 half-lives of the drug, whichever is longer;

3. The Chinese medicine with antitumor indications is within 2 weeks before the first use of the study drug.

• Received other unmarketed investigational drugs or treatments within 4 weeks prior to the first use of the investigational drug;

• Received live/attenuated vaccine and mRNA vaccine within 4 weeks prior to screening or plan to receive live/attenuated vaccine and mRNA vaccine during the study period;

• Pregnant or lactating women;

• Patients whose AE caused by previous anti-tumor therapy did not recover to CTCAE 5.0≤ 1; (except for toxicities determined by the investigator to have no safety risk, such as hair loss, grade 2 peripheral neurotoxicity, hypothyroidism stabilized by hormone replacement therapy, etc.);

• Patients with cerebral parenchymal metastasis or meningeal metastasis with clinical symptoms, judged by the investigator to be unsuitable for inclusion;

• Patients who underwent major organ surgery (excluding needle biopsy) or significant trauma within 4 weeks prior to the first use of the study drug, or who required elective surgery during the study period;

• Those with a history of tissue or organ transplantation;

• Patients with active infection prior to the first administration and currently requiring intravenous anti-infection therapy;

• Known history of human immunodeficiency virus (HIV) infection;

• active hepatitis B;

Note: Hepatitis B subjects who meet the following criteria may not be excluded:

A. HBV viral load must be < 500IU/ml or lower than the lower limit of the study center before initial administration (only if the lower limit of the study center is higher than 500IU/ml), and the investigator should consider anti-HBV therapy during the study period; B. Subjects who are resistant to HBc (+), HBsAg (-), anti-HBS (-), and HBV viral load (-) do not need prophylactic anti-HBV therapy, but close monitoring of virus reactivation is required;

• Active HCV-infected subjects (HCV antibody positive and HCV-RNA level higher than the detection limit);

• Subjects with untreated or undergoing treatment for tuberculosis, including but not limited to tuberculosis; Patients who have been prescribed anti-tuberculosis therapy and confirmed by the investigator to have been cured may be included;

• The subject is known to have a history of severe allergy, or is known to have experienced grade ≥3 allergic reactions to macromolecular protein preparations/monoclonal antibodies in the past;

• Patients who have active autoimmune diseases, or have had autoimmune diseases with recurrence risk (such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.), except patients with clinically stable autoimmune thyroid diseases and type I diabetes;

• Received systemic glucocorticoid (prednisone > 10mg/ day or equivalent dose of the same drug) or other immunosuppressant treatment within 14 days prior to first use of the study drug; The exceptions are local, ocular, intraarticular, intranasal, and inhaled glucocorticoid therapy and short-term prophylaxis (e.g., to prevent contrast agent allergies).

• IrAE ≥3 has been seen in the past;

• existing interstitial lung disease;

• Have a history of serious cardiovascular and cerebrovascular diseases, including but not limited to:

1. Severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmia, ⅱ - ⅲ degree ATrioventricular block, etc., requiring clinical intervention;

2. Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other grade 3 or higher cardiovascular and cerebrovascular events occurred within 6 months prior to first administration;

• Presence of heart failure or left ventricular ejection fraction (LVEF) < 50% with the New York Heart Association (NYHA) cardiac function rating ≥II

• clinically uncontrolled hypertension (defined in this protocol as systolic blood pressure > 150mmHg and/or diastolic blood pressure > 100mmHg after treatment despite antihypertensive therapy);

• Third interstitial effusion that could not be controlled clinically was judged not suitable for inclusion by the researcher;

• Patients with a known history of psychotropic drug abuse or drug use that is considered to affect the compliance of this study;

• Patients considered unsuitable for the study by the investigator.