Phase I Clinical Trial to Evaluate the Tolerability, Pharmacokinetics, and Preliminary Efficacy of TQB3205 Capsule in Subjects With Advanced Malignant Tumors
Overview
- Phase
- Phase 1
- Status
- Recruiting
- Enrollment
- 156
- Locations
- 1
- Primary Endpoint
- Dose Limiting Toxicity (DLT)
Overview
Brief Summary
The trial was divided into two phases: dose escalation and dose expansion. The dosing regimens were single-dose study and continuous dosing study. A single-center, open, non-randomized, single-arm clinical trial design was adopted. Subjects with advanced malignant tumors were selected to take TQB3205 capsules orally to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of TQB3205 capsules.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Subjects voluntarily joined the study, signed informed consent form, and with good compliance.
- •≥18 years old; Eastern Cooperative Oncology Group (ECOG) physical status: 0-1; at least 3 months expected survival period.
- •At least 1 measurable lesion for efficacy evaluation.
- •The function of main organs is normal.
- •Women of childbearing age should agree to use effective contraceptive measures during the study period and within 6 months after the end of the study, and have a negative serum or urine pregnancy test within 7 days before enrollment in the study; Men should agree to use effective contraceptive measures during the study period and within 6 months after the end of the study period.
Exclusion Criteria
- •Individuals who have undergone major surgical treatment, significant traumatic injury, or major surgery during the expected study treatment period within 4 weeks prior to the first medication (excluding surgeries specified in the protocol), or have long-term untreated wounds or fractures. (Major surgery is defined as surgery at level 3 or above in the National Surgical Classification Catalogue 2022 edition);
- •Subjects who experience any bleeding or bleeding events ≥ CTC AE grade 3 within 4 weeks prior to the first administration.
- •Active syphilis infected individuals in need of treatment
- •Individuals with a history of abuse of psychotropic drugs who are unable to quit or have mental disorders;
- •Individuals who are preparing for or have previously undergone allogeneic bone marrow transplantation or solid organ transplantation;
- •History of hepatic encephalopathy;
- •Active or uncontrolled infections (≥ CTC AE level 2 infection);
- •Patients with renal failure requiring hemodialysis or peritoneal dialysis;
- •History of immunodeficiency, including HIV positivity or other acquired or congenital immunodeficiency diseases;
- •Individuals with epilepsy who require treatment;
Arms & Interventions
TQB3205 capsules
Single or continuous administration, 6-36 mg each time; TQB3205 capsule is taken orally once a day on an empty stomach, and each cycle is 21 days.
Intervention: TQB3205 capsules (Drug)
Outcomes
Primary Outcomes
Dose Limiting Toxicity (DLT)
Time Frame: At the end of Cycle 1 (each cycle is 21 Days)
DLT will be defined as toxicities that meet pre-defined severity criteria(according to the NCI Common Terminology Criteria for Adverse Events(CTCAE) version6.0 toxicity assessment criteria), and assessed as having a suspected relationship to study drug that occurred from first medication to the end of the first treatment cycle.
Maximum tolerated dose (MTD)
Time Frame: At the end of Cycle 1 (each cycle is 21 Days)
MTD was defined as the highest dose at which dose-limiting toxicity (DLT) occurred in less than 33% of patients.
Recommended Phase II Dose (RP2D)
Time Frame: Baseline up to 24 months
RP2D describes side effects of a drug or other treatment that are serious enough to evaluate RP2D of TQB3205 capsules in adult patients with Advanced Malignant Cancer
Maximum assessed dose (MAD)
Time Frame: Baseline up to 24 months
Recommendations made by the investigator and sponsor based on clinical safety, efficacy, Pharmacokinetics (PK), and Pharmacodynamics (PD) data will be considered the highest dose level to complete dose exploration in the absence of an Maximum Tolerated Dose (MTD).
The occurrence of all adverse events (AEs)
Time Frame: From the time the subject receives TQB3205 to 28 days after the last dose or until the start of other anti-tumor treatment (whichever occurs first, up to approximately 3 years)
The occurrence of all adverse events (AEs)
The occurrence of all serious adverse events (SAEs)
Time Frame: From the time the subject receives TQB3205 to 28 days after the last dose or until the start of other anti-tumor treatment (whichever occurs first, up to approximately 3 years)
The occurrence of all serious adverse events (SAEs).
Number of subjects with abnormal incidence of laboratory test indicators
Time Frame: From the time the subject receives TQB3205 to 28 days after the last dose or until the start of other anti-tumor treatment (whichever occurs first, up to approximately 3 years)
Number of subjects with abnormal incidence and severity of laboratory test indicators .
Secondary Outcomes
- Overall response rate (ORR)(From date of the first dose until the date of first documented progression or date of death from any cause, up to approximately 3 years)
- Tmax(Single Day 1: 0.5 hour pre-dose, 1, 2, 3,4, 6, 8, 12,24,48,72,96,144 hours after-dose. Cycle1 Day 1: 0.5 hour pre-dose,1, 2, 3,4, 6, 8, 12,24 hours after-dose. Cycle 1 Day 21: at 30 minutes,1, 2, 3, 4, 6, 8, 12,24 hours after-dose.(21 days is a cycle))
- Cmax(Single Day 1: 0.5 hour pre-dose, 1, 2, 3,4, 6, 8, 12,24,48,72,96,144 hours after-dose. Cycle1 Day 1: 0.5 hour pre-dose,1, 2, 3,4, 6, 8, 12,24 hours after-dose. Cycle 1 Day 21: at 30 minutes,1, 2, 3, 4, 6, 8, 12,24 hours after-dose.(21 days is a cycle))
- Elimination half-life (t1/2)(Single Day 1: 0.5 hour pre-dose, 1, 2, 3,4, 6, 8, 12,24,48,72,96,144 hours after-dose. Cycle1 Day 1: 0.5 hour pre-dose,1, 2, 3,4, 6, 8, 12,24 hours after-dose. Cycle 1 Day 21: at 30 minutes,1, 2, 3, 4, 6, 8, 12,24 hours after-dose.(21 days is a cycle))
- Area under the plasma concentration-time curve from time zero to time t (AUC0-t)(Single Day 1: 0.5 hour pre-dose, 1, 2, 3,4, 6, 8, 12,24,48,72,96,144 hours after-dose. Cycle1 Day 1: 0.5 hour pre-dose,1, 2, 3,4, 6, 8, 12,24 hours after-dose. Cycle 1 Day 21: at 30 minutes,1, 2, 3, 4, 6, 8, 12,24 hours after-dose.(21 days is a cycle))
- Apparent clearance (CL/F)(Single Day 1: 0.5 hour pre-dose, 1, 2, 3,4, 6, 8, 12,24,48,72,96,144 hours after-dose. Cycle1 Day 1: 0.5 hour pre-dose,1, 2, 3,4, 6, 8, 12,24 hours after-dose. Cycle 1 Day 21: at 30 minutes,1, 2, 3, 4, 6, 8, 12,24 hours after-dose.(21 days is a cycle))
- Apparent volume of distribution (Vd/F)(Single Day 1: 0.5 hour pre-dose, 1, 2, 3,4, 6, 8, 12,24,48,72,96,144 hours after-dose. Cycle1 Day 1: 0.5 hour pre-dose,1, 2, 3,4, 6, 8, 12,24 hours after-dose. Cycle 1 Day 21: at 30 minutes,1, 2, 3, 4, 6, 8, 12,24 hours after-dose.(21 days is a cycle))
- Minimum concentration (Cminutes)(Single Day 1: 0.5 hour pre-dose, 1, 2, 3,4, 6, 8, 12,24,48,72,96,144 hours after-dose. Cycle1 Day 1: 0.5 hour pre-dose,1, 2, 3,4, 6, 8, 12,24 hours after-dose. Cycle 1 Day 21: at 30 minutes,1, 2, 3, 4, 6, 8, 12,24 hours after-dose.(21 days is a cycle))
- Disease Control Rate (DCR)(From date of the first dose until the date of first documented progression or date of death from any cause, assessed up to 100 weeks)
- Duration of Response (DOR)(From date of the first dose until the date of first documented progression or date of death from any cause, assessed up to 100 weeks)
- Progression Free Survival (PFS)(From date of the first dose until the date of first documented progression or date of death from any cause, assessed up to 100 weeks)
- Overall Survival (OS)(From the date of first medication use to the date of death from any cause, assessed up to 100 weeks)