Advanced Malignancies
Conditions
Brief summary
TQB6426 is a glypican-3 (GPC3)-targeted antibody-drug conjugate (ADC) independently developed by Chia Tai Tianqing Pharmaceutical Group Co., Ltd. Preclinical studies have demonstrated its potent anti-tumor activity coupled with a favorable therapeutic safety window, which provides sufficient pharmacological and toxicological evidence to support the initiation of human clinical trials.
Interventions
DRUGTQB6426 for Injection
TQB6426 is a glypican-3 (GPC3)-targeted antibody-drug conjugate (ADC) independently developed by Chia Tai Tianqing Pharmaceutical Group Co., Ltd. Preclinical studies have demonstrated its potent anti-tumor activity coupled with a favorable therapeutic safety window, which provides sufficient pharmacological and toxicological evidence to support the initiation of human clinical trials.
Sponsors
Shanghai Chia Tai Tianqing Pharmaceutical Technology Development Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Study participants voluntarily enroll in this study, sign the informed consent form, and demonstrate good treatment compliance. 2. Age ranging from 18 to 75 years (calculated based on the date of informed consent signature). 3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. 4. Estimated survival time exceeding 12 weeks. 5. Child-Pugh liver function score ≤ 7 points (Class B). 6. Per RECIST v1.1 criteria, at least one evaluable tumor lesion must be identified as a target lesion. Lesions previously treated with local therapy (transarterial embolization, transarterial chemoembolization, transarterial radioembolization, surgery, radiofrequency ablation, microwave ablation, other thermal ablation, percutaneous ethanol injection, radiotherapy, etc.) may also serve as target lesions provided there is documented progression in such lesions. 7. Participants must provide qualified tumor tissue specimens, or consent to submit archived tumor tissue samples, or undergo percutaneous core biopsy or surgical biopsy on previously unirradiated tumor lesions to supply specimens for central laboratory biomarker testing. 8. Dose-escalation phase: Advanced solid tumors confirmed via histopathological or cytological examination with failure of prior standard systemic anti-tumor therapies. 9. Dose-expansion phase: Glypican-3 (GPC3) positivity confirmed by immunohistochemistry (IHC); prior IHC test reports are acceptable. 10. Hematology laboratory criteria (no blood transfusion/blood products or hematopoietic stimulating factor administration within 14 days prior to screening): Absolute Neutrophil Count (ANC) ≥ 1.5 × 10⁹/L; Platelet count ≥ 100 × 10⁹/L; Hemoglobin ≥ 90 g/L. 11. Serum biochemistry laboratory criteria: 1) Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤ 3 × Upper Limit of Normal (ULN); for patients with intrahepatic metastases, ALT and AST ≤ 5 × ULN; 2) Total Bilirubin (TBIL) ≤ 3 × ULN (≤ 3 × ULN allowed for patients with Gilbert's syndrome); 3) Serum albumin ≥ 28 g/L; 4) Serum Creatinine (Cr) ≤ 1.5 × ULN, or estimated creatinine clearance ≥ 50 mL/min calculated via the Cockcroft-Gault formula. 12. Urinalysis criteria: Urine protein \< 2+ on routine urinalysis; if urine protein ≥ 2+, 24-hour urinary protein quantification must be confirmed ≤ 1.0 g. 13. Coagulation function criteria: Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT), and International Normalized Ratio (INR) ≤ 1.5 × ULN (for patients without prior anticoagulant therapy). 14. Thyroid function criteria: Thyroid-Stimulating Hormone (TSH) ≤ ULN; participants with abnormal TSH but normal free T3 and free T4 levels are eligible for enrollment. 15. Women of childbearing potential must agree to use effective contraception throughout the study and for 6 months after study completion, and have a negative serum pregnancy test within 7 days prior to enrollment. Male participants must agree to use effective contraception throughout the study and for 6 months following study completion.
Exclusion criteria
1.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-Limiting Toxicity (DLT) | Baseline to 21 days | Study participants experienced protocol-specified adverse events related to the investigational drug within one cycle (21 days) of receiving the investigational drug. |
| Maximum Tolerated Dose | Baseline to the end of the first treatment cycle (each cycle is 21 days） | The highest dose at which less than 33% of study participants experience dose-limiting toxicity (DLT) |
| Recommended Phase II Dose | Baseline to study completion (up to 24 months). | The dose level of TQB6426 recommended for the further clinical trail studies based on assessment of the safety, efficacy and PK data from this study. |
| Incidence and severity of adverse events (AEs) | up to 24 months | Incidence and severity of adverse events (AEs) |
| Maximum Administered Dose | Baseline to the end of the first treatment cycle (each cycle is 21 days） | MAD is defined to be reached if, following the pre-specified dose escalation, a dose-exposure plateau is achieved as judged by PK data, or further dose escalation carries substantial safety risks or subjects cannot tolerate continued dose increase based on available safety data, or model analysis indicates that the optimal safe and effective target dose has been explored. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Concentration (Cmax) | up to 24 months | Cmax refers to the maximum drug concentration in plasma after administration. |
| Area under the plasma drug concentration-time curve from time zero to the time of the last accurately quantifiable concentration (AUC0-t) | up to 24 months | AUC0-t refers to the total systemic exposure to the drug from the time of administration until the last accurately quantifiable concentration is observed. |
| Area under the plasma concentration-time curve extrapolated from time zero to infinite time（AUC0-∞） | up to 24 months | AUC0-∞ refers to the total systemic exposure to the drug from the time of administration to infinite time . |
| Time to peak concentration (Tmax) | up to 24 months | The time from drug administration to the time point of the maximum observed plasma drug concentration. |
| Terminal Elimination Rate Constant（λz） | up to 24 months | First-order rate constant governing the elimination of drug from plasma during the terminal log-linear elimination phase. |
| Terminal Elimination Half-Life (t1/2) | up to 24 months | The time required for the plasma drug concentration to decrease by one-half during the terminal elimination phase. |
| Apparent Clearance (CL) | up to 24 months | Apparent clearance following extravascular administration, calculated as Dose / AUC0-∞ |
| Apparent Volume of Distribution (Vd) | up to 24 months | Volume of Distribution (Vd) is a pharmacokinetic parameter that refers to the ratio of the total amount of drug in the body to its plasma concentration when the drug reaches a dynamic equilibrium in the body. |
| Percentage of extrapolated AUC0-∞ (%AUCextrap) | up to 24 months | The percentage of AUC0-∞ extrapolated refers to the percentage of the area extrapolated from the last accurately quantifiable concentration to infinity (AUCextrap) relative to the total AUC0-∞. It is used to evaluate the reliability of the AUC0-∞ estimation. |
| Incidence of anti-drug antibodies (ADAs) | up to 24 months | Anti-drug antibodies (ADAs) are immune system-produced antibodies that specifically bind to therapeutic drugs (especially biologics or monoclonal antibodies). The development of ADAs can alter the drug's pharmacokinetics, reduce its clinical efficacy, or cause safety issues such as hypersensitivity reactions. |
| Objective Response Rate（ORR） | up to 24 months | The proportion of subjects with confirmed complete response (CR) or partial response (PR). |
| Duration of Response （DOR） | up to 24 months | The time from the date of first confirmed complete response (CR) or partial response (PR) to the date of first documented progressive disease (PD) or death from any cause, whichever occurs first. |
| Disease Control Rate（DCR） | up to 24 months | The proportion of subjects achieving complete response, partial response or stable disease. |
| Progression-Free Survival （PFS） | up to 24 months | The time from the first dose of study drug to the date of first documented disease progression or death from any cause, whichever occurs first. |
| Overall Survival（OS） | up to 24 months | The time from first dose of study drug to date of death from any cause. |
Countries
China
Contacts
CONTACTQiang Xia, Doctor
Outcome results
None listed