A Clinical Trial of TQB6426 for Injection in Patients With Advanced Solid Tumors

Официальное название

A Phase I Clinical Trial Evaluating the Tolerability and Pharmacokinetics of TQB6426 for Injection in Patients With Advanced Malignancies

Обзор

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.

Вмешательства

• Препарат TQB6426 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.

Первичные конечные точки

• Dose-Limiting Toxicity (DLT) [Срок оценки: Baseline to 21 days]
• Maximum Tolerated Dose [Срок оценки: Baseline to the end of the first treatment cycle (each cycle is 21 days）]
• Recommended Phase II Dose [Срок оценки: Baseline to study completion (up to 24 months).]
• Incidence and severity of adverse events (AEs) [Срок оценки: up to 24 months]

Вторичные конечные точки (12)

• Maximum Concentration (Cmax) [Срок оценки: up to 24 months]
• Area under the plasma drug concentration-time curve from time zero to the time of the last accurately quantifiable concentration (AUC0-t) [Срок оценки: up to 24 months]
• Area under the plasma concentration-time curve extrapolated from time zero to infinite time（AUC0-∞） [Срок оценки: up to 24 months]
• Time to peak concentration (Tmax) [Срок оценки: up to 24 months]
• Terminal Elimination Rate Constant（λz） [Срок оценки: up to 24 months]
• Terminal Elimination Half-Life (t1/2) [Срок оценки: up to 24 months]
• Apparent Clearance (CL/F) [Срок оценки: up to 24 months]
• Apparent Volume of Distribution (Vz/F) [Срок оценки: up to 24 months]
• Percentage of extrapolated AUC0-∞ (%AUCextrap) [Срок оценки: up to 24 months]
• Incidence of anti-drug antibodies (ADAs) [Срок оценки: up to 24 months]
• Objective Response Rate（ORR） [Срок оценки: up to 24 months]
• Duration of Response （DOR） [Срок оценки: up to 24 months]

Критерии участия

Критерии включения

• Study participants voluntarily enroll in this study, sign the informed consent form, and demonstrate good treatment compliance.
• Age ranging from 18 to 75 years (calculated based on the date of informed consent signature).
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Estimated survival time exceeding 12 weeks.
• Child-Pugh liver function score ≤ 7 points (Class B).
• Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1): - Dose-escalation phase: At least one evaluable tumor lesion; - Dose-expansion phase: At least one measurable tumor lesion. Target lesions must not have received prior local therapies, including transarterial embolization (TAE), transarterial chemoembolization (TACE), transarterial radioembolization (TARE), surgery, radiofrequency ablation (RFA), microwave ablation (MWA), other thermal ablation, percutaneous ethanol injection (PEI), radiotherapy, etc.
• 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.
• Dose-escalation phase: Advanced solid tumors confirmed via histopathological or cytological examination with failure of prior standard systemic anti-tumor therapies.
• Dose-expansion phase: Glypican-3 (GPC3) positivity confirmed by immunohistochemistry (IHC); prior IHC test reports are acceptable.
• 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.
• 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.
• Urinalysis criteria: Urine protein < 2+ on routine urinalysis; if urine protein ≥ 2+, 24-hour urinary protein quantification must be confirmed ≤ 1.0 g.
• 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).
• Thyroid function criteria: Thyroid-Stimulating Hormone (TSH) ≤ ULN; participants with abnormal TSH but normal free T3 and free T4 levels are eligible for enrollment.
• 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.

Критерии исключения

• Exclusion Criteria Subjects satisfying any of the following criteria shall be excluded from this trial: Prior treatment with GPC3-targeted agents or other antibody-drug conjugates (ADCs) utilizing topoisomerase I inhibitors as cytotoxic payloads.
• Diagnosis of another malignant tumor within 5 years prior to the first study dose, or concurrent secondary malignancy at screening. Eligible exceptions are as follows: other malignancies cured by single surgical resection with a continuous 5-year disease-free survival (DFS); cured cervical carcinoma in situ, papillary thyroid carcinoma, non-melanoma skin cancer, and superficial bladder tumors \[Ta (non-invasive carcinoma), Tis (carcinoma in situ), T1 (tumor invading lamina propria)\].
• Medical conditions interfering with intravenous injection or venous blood collection (including but not limited to active phlebitis, severe lymphedema, extensive cutaneous infection, etc.).
• Unresolved adverse toxicities higher than CTCAE Grade 1 stemming from prior therapies, excluding alopecia, skin pigmentation, and toxicities deemed by the Investigator to carry no safety risks.
• Major surgical procedures, significant traumatic injuries within 4 weeks before the first dose, or persistent unhealed wounds/fractures.
• Any hemorrhagic event ≥ CTCAE Grade 3 occurring within 4 weeks prior to the first administration of study drug.
• History of arterial or venous thromboembolic events within 6 months before the first dose, such as cerebrovascular accidents (including transient ischemic attacks), deep vein thrombosis, pulmonary embolism, or any other severe thromboembolism. (Note: Thrombosis related to implantable venous access ports, catheter-induced thrombosis, or superficial venous thrombosis shall not be categorized as "severe" thromboembolism.)
• Poorly controlled active viral hepatitis. Subjects meeting the below criteria may proceed to screening: HBsAg-positive participants with HBV DNA < 2000 IU/mL (or 10,000 copies/mL) who agree to continuous anti-HBV therapy throughout the study; participants with HCV infection requiring treatment may receive approved antiviral regimens during the trial.
• Imaging confirmation of inferior vena cava tumor thrombus, complete occlusion of the main portal vein (tumor thrombus or blood thrombus), concurrent tumor thrombus invasion of the main portal vein plus primary branches, or portal vein tumor thrombus extending into the superior mesenteric vein, splenic vein or more proximal vessels.
• Peptic ulcer disease or inflammatory bowel disease.
• Active syphilis infection requiring clinical treatment.
• Active pulmonary tuberculosis, history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis/radiation pneumonitis requiring treatment, symptomatic active pneumonia; prior interstitial lung disease (ILD) that required intervention or current ILD.
• History of untreatable psychoactive substance abuse or diagnosed psychiatric disorders.
• Candidates scheduled for allogeneic bone marrow transplantation or solid organ transplantation, or those who have received such transplantations previously.
• Documented history of hepatic encephalopathy.
• Subjects with any severe and/or uncontrolled underlying diseases, including:

1\) Uncontrolled hypertension (systolic BP ≥ 150 mmHg or diastolic BP ≥ 100 mmHg); 2) Poorly managed cardiac symptoms or disorders: a. Myocardial ischemia or myocardial infarction ≥ Grade 2, congestive heart failure ≥ NYHA Class II; b. Myocardial infarction within the past 12 months; c. Arrhythmias: Fridericia-corrected QT interval (QTcF) > 450 msec in males and > 470 msec in females. If QTcF is abnormal, three serial measurements separated by at least 2 minutes shall be performed and the average value adopted; frequent ventricular premature contractions, significant sinus bradycardia, or other conditions assessed by the Investigator and relevant departments to confer high risk of malignant arrhythmia, or other conditions judged by the Investigator to predispose to malignant arrhythmia.

3\) Active or uncontrolled severe infections (≥ CTCAE Grade 2 infection); 4) Evidence of bleeding diathesis or severe coagulopathy; 5) Current or recent use (within 10 days prior to first study treatment) of aspirin (>325 mg/day), dipyridamole, ticlopidine, clopidogrel, cilostazol, or other anticoagulant/antiplatelet agents; 6) Renal failure requiring hemodialysis or peritoneal dialysis; 7) History of immunodeficiency, including HIV positivity or other acquired/congenital immunodeficiency disorders; 8) Subjects requiring immunosuppressants, systemic hormones, or absorbable topical hormones for immunosuppressive purposes and continuing such treatment within 7 days before the first dose (excluding glucocorticoids at a daily dose equivalent to <10 mg prednisone); 9) Diagnosed epilepsy requiring ongoing treatment; 10) Poorly controlled diabetes (fasting blood glucose \[FBG\] > 10 mmol/L); 11) History of gastrointestinal hemorrhage within 6 months before the first dose; portal hypertension with high bleeding risk as assessed by the Investigator, or positive red color sign on gastroscopy.

(17) Tumor-related symptoms and prior anti-tumor therapies:

• Subjects who received chemotherapy or immunotherapy within 2 weeks before the first dose, endovascular interventional therapy, local ablation, radiotherapy or small-molecule targeted agents within 2 weeks before the first dose, or remain within 5 half-lives of the last administered drug (the shorter time frame shall prevail). The washout period shall be calculated from the date of completion of the last prior anti-tumor treatment.
• Treatment with Chinese patent medicines with anti-tumor indications clearly stated in NMPA-approved labeling within 2 weeks before the first dose (including Compound Mylabris Capsules, Kang'ai Injection, Kanglaite Capsules/Injection, Aidi Injection, Brucea Javanica Oil Injection/Capsules, Xiaoaiping Tablets/Injection, Huachansu Capsules, etc.).
• CT/MRI imaging showing tumor invasion into major blood vessels, or tumors assessed by the Investigator to have high risk of invading critical vessels and triggering fatal massive hemorrhage during the trial (e.g., tumors adjacent to or encasing the pulmonary artery or aorta).
• Uncontrolled pleural effusion, pericardial effusion, or moderate to severe ascites requiring repeated drainage.
• Severe biliary obstruction (excluding subjects with total bilirubin ≤ 2 × ULN after endoscopic stenting, percutaneous transhepatic biliary drainage or other interventions).
• Confirmed spinal cord compression, pathological fractures of weight-bearing bones, extensive bone metastases, or intractable tumor-related bone pain.
• Carcinomatous meningitis, symptomatic brain metastases, or brain metastases with symptom control lasting less than 4 weeks. 8) Spontaneous tumor rupture or high risk of impending tumor rupture.

(18) Known hypersensitivity to the study drug or its excipients. (19) Participation in another clinical trial of anti-tumor investigational products with study drug administration within 4 weeks before the first dose.

(20) Lactating female subjects. (21) Any condition judged by the Investigator to pose substantial safety risks to the subject or impair the subject's ability to complete the trial.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 8 центров

• The First Affiliated Hospital of Anhui Medical University — Хэфэй
• Peking University First Hospital — Пекин
• Fujian Provincial Hospital — Фучжоу
• ZhuJiang Hospital of Southern Medical University — Гуанчжоу
• Harbin Medical University Cancer Hospital — Харбин
• Henan Cancer Hospital — Чжэнчжоу
• Hunan Cancer Hospital — Чанша
• Renji Hospital, Shanghai Jiao Tong University School of Medicine — Шанхай

Идентификаторы

NCT: NCT07730190 · TQB6426-I-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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