A Multicenter, Open Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics and Preliminary Clinical Efficacy of Anti-Tigitmab BAT6005 Injection in Patients with Advanced Malignant Solid Tumors
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Enrollment
- 28
- Locations
- 2
- Primary Endpoint
- Dose-limiting toxicity(DLT)
Study Overview
Brief 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.
Detailed Description
The study is divided into two parts:
Part I: single drug dose escalation study. Accelerated titration and "3+3" dose escalation rule were used to explore the safety, tolerability and pharmacokinetic characteristics of BAT6005.
Since the clinical benefit of a single agent may be limited, the study used accelerated titration and the "3+3" dose-escalation rule to explore the safe dose range from the ethical point of view of exposing fewer subjects to ineffective doses.
Six dose groups were set up, including 10mg (initial dose) group, 30mg group, 100mg group, 300mg group, 600mg group and 900mg group, respectively.
The whole is divided into two phases. The first stage: 10mg group, 30mg group, 100mg group using accelerated titration method to increase the dose.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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;
- •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
- •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;
- •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;
- •Active HCV infected subjects
- •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;
- •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.
Arms & Interventions
BAT6005 single drug dose escalation study
The whole is divided into two phases.The first stage: 10mg group, 30mg group, 100mg group using accelerated titration method to increase the dose.The second stage: 300mg group, 600mg group, 900mg group according to the standard "3+3" rule dose increase study.
Intervention: BAT6005 injection (Drug)
Outcomes
Primary Outcomes
Dose-limiting toxicity(DLT)
Time Frame: Complete the first cycle in 21 days
AE that occur during the dose-limiting toxicity observation period and are considered to be at least possibly related to the drug under study.
Maximum Tolerated dose (MTD)
Time Frame: Complete the first cycle in 21 days
The highest dose level of DLT observed in ≤1/6 subjects in a dose group during the DLT evaluation period.
Secondary Outcomes
- Maximum serum drug time(Tmax)(0-126days)
- Half-life period(t1/2)Pharmacokinetic endpoint(0-126days)
- Plasma clearance(CL)Pharmacokinetic endpoint(0-126days)
- Apparent Volume of Distribution（Vd）(0-126days)
- Effect Chamber Elimination Rate Constant（Ke）(0-126days)
- Mean Residence Time（MRT）(0-126days)
- Area under the curve(AUC0-t, AUC0-inf)(0-126days)
- Maximum serum drug concentration(Cmax)Pharmacokinetic endpoint(0-126days)
- Anti-drug antibodies(ADA)Immunogenic endpoint(0-126days)
- Prevalence of PD-1 receptors on peripheral blood T cells（RO）(0-126days)