Advanced Malignant Cancer
Conditions
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.
Interventions
DRUGTQB3205 capsules
TQB3205 capsule is a targeted protein degrader
Sponsors
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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; * Poor control of diabetes (assessed by the investigator); * Known to be allergic to research drugs or excipients; * Those who have participated in and used other anti-tumor clinical trial drugs within 4 weeks before the first medication; * According to the researcher's judgment, there is a situation that seriously endangers the safety of the subjects or affects their ability to complete the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Limiting Toxicity (DLT) | 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) | 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) | 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) | 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) | 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) | 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 | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | The proportion of subjects with best response of Complete response, partial response, Very good partial response, and Minimal response. |
| 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) | Time to Reach the Maximum Plasma Concentration |
| 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) | Cmax is the maximum plasma concentration of TQB3205. |
| 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) | To evaluate the elimination half-life (t1/2) after oral dose of TQB3205 capsules to subjects. |
| 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) | To characterize the pharmacokinetics of TQB3205 by assessment of area under the plasma concentration time curve from the first dose to a certain time. |
| 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) | Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the body. |
| 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) | Apparent volume of distribution of the TQB3205 in plasma. |
| 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) | Minimum observed concentration (Cminutes) of TQB3205 |
| 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 | The percentage of patients with advanced or metastatic cancer who have achieved complete response, partial response and stable disease to a cancer treatment in clinical trials. |
| 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 | The time from the date of first documentation of a CR or PR or PD to the date of first documentation of tumor progression. |
| 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 | The time from the first dose to the first documentation of progressive disease (PD) or death from any cause, whichever occurs first. |
| Overall Survival (OS) | From the date of first medication use to the date of death from any cause, assessed up to 100 weeks | The time from start of study treatment to date of death due to any cause |
Countries
China
Contacts
CONTACTJihui Hao, Doctor
Outcome results
None listed