TQB3201 is an orally administered targeted protein chimera (PROTAC) drug in which one end of the drug is attached to a ligand that binds to Androgen Receptor (AR) and the other end to a ligand of E3 ligase (CRBN) via a linker. The phase I phase of this trial aims to evaluate the safety, tolerability, and pharmacokinetic characteristics of TQB3201 tablets for the treatment of advanced prostate cancer.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
291
TQB3201 is an orally administered targeted protein chimera (PROTAC) drug in which one end of the drug is attached to a ligand that binds to AR and the other end to a ligand of E3 ligase (CRBN) via a linker. This product is effective against anti-androgen drugs (such as abiraterone, enzalutamide, etc.) resistance mutations, including AR amplification, point mutations (L702H, H875Y, T878A mutations, etc.), and can target the degradation of wild-type AR and AR ligand-binding domain mutants, especially L702H mutations, which is a new generation of AR-PROTAC.
Cancer Hospital Affiliated to Chongqing University
Chongqing, Chongqing Municipality, China
The Fifth Affiliated Hospital of Sun Yat-sen University
Zhuhai, Guangdong, China
Cancer Hospital Affiliated to Fudan University
Shanghai, Shanghai Municipality, China
Dose Limiting Toxicity (DLT)
DLTs are defined as toxicities that occur from the first dose to the end of the first treatment cycle by the severity criteria related to the trial drug (according to Common Terminology Criteria for Adverse Events v5.0 toxicity evaluation criteria) .
Time frame: Up to 28days
Maximum tolerated dose (MTD)
The MTD was defined as the highest dose in ≥ 6 evaluable subjects without any of the following: 1. In the DLT evaluation window, DLT occurred in 2 out of 3 subjects; 2. In the DLT evaluation window, 1 of the first 3 subjects had DLT, and 3 more subjects were added and 1 case had ≥ DLT.
Time frame: Up to 28days
Phase II Recommended Dose (RP2D)
The RP2D will be determined based on the safety and tolerability information of the Phase I dose escalation phase and the efficacy and safety information of the Phase II phase.
Time frame: Up to 2 years
Radiographic progression-free survival (rPFS)
The time from randomization to the first occurrence of either radiologically confirmed disease progression or death from any cause, whichever comes first.
Time frame: Up to 2 years
Adverse events (AEs)
Incidence and severity of adverse events, as determined by the NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0 grading scale. Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) and abnormal laboratory values.
Time frame: Up to 2 years
The area under the curve (AUC)
The area under the curve (AUC) of serum concentration of TQB3201.
Time frame: cycle1 day1pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours after dose, cycle1 day7, 14 pre-dose, cycle1 day 28 pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours after dose
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Peak concentration (Cmax)
Maximum observed concentration (Cmax) of TQB3201 antibody
Time frame: cycle1 day1pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours after dose, cycle1 day7, 14 pre-dose, cycle1 day 28 pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours after dose
Terminal half-life (T1/2)
Terminal half-life (T1/2)
Time frame: cycle1 day1pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours after dose, cycle1 day7, 14 pre-dose, cycle1 day 28 pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours after dose
Apparent Clearance (CL/F)
Apparent clearance refers to the rate of drug removal in the body, which reflects the degree of drug elimination in the body, as well as the bioavailability of the drug in the body.
Time frame: cycle1 day1pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours after dose, cycle1 day7, 14 pre-dose, cycle1 day 28 pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours after dose
Volume of Distribution at Steady State (Vss/F)
When the drug distribution in plasma and tissue reaches equilibrium, the drug distribution in the body body according to the plasma drug concentration at this time is the required body fluid volume called apparent distribution volume.
Time frame: cycle1 day1pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours after dose, cycle1 day7, 14 pre-dose, cycle1 day 28 pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours after dose
Objective Response Rate (ORR)
Patients with soft tissue (nodes, visceral) lesions that can be evaluated according to RECIST 1.1 criteria, the proportion of cases with the best total response of soft tissue lesions as confirmed complete response (CR) and confirmed partial response (PR).
Time frame: Up to 2 years
Prostate-Specific Antigen Response Rate
Percentage of subjects whose Prostate-Specific Antigen (PSA) decreased by more than 50% from baseline and maintained for more than 4 weeks.
Time frame: Up to 2 years
To PSA progression time
Refers to the time from the start of randomization to the confirmation of PSA progression.
Time frame: Up to 2 years
Time to symptomatic bone-related events (SSEs)
Refers to the time from the randomization date to the first occurrence of symptomatic bone-related events, including the use of external beam radiation therapy (EBRT) to prevent or relieve bone symptoms, the development of new symptomatic pathological fractures (vertebral or non-vertebrae), spinal cord compression, and tumor-related orthopedic surgical intervention, whichever occurs first. Symptomatic bone-related events do not include asymptomatic fractures identified by imaging.
Time frame: Up to 2 years
Overall Survival (OS)
Refers to the time from randomization to death from any cause.
Time frame: Up to 2 years