Clinical Trial of TQB3126 for Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy in Breast Cancer Subjects

Официальное название

Phase I/II Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of TQB3126 in Subjects With Breast Cancer

Обзор

The trial comprises Phase I dose escalation/expansion and Phase II combination therapy. Using a multicenter, open-label, non-randomized design, breast cancer patients will receive TQB3126 to assess its safety, tolerability, pharmacokinetics and preliminary efficacy.

Вмешательства

• Препарат TQB3126
  TQB3126 is a targeted protein degrader.

Первичные конечные точки

• Dose Limiting Toxicity (DLT) [Срок оценки: From first dose of TQB3126 to the end of Cycle 1, approximately 35 days.]
• Maximum Tolerated Dose (MTD) [Срок оценки: From first dose of TQB3126 to the end of Cycle 1, approximately 35 days.]
• Recommended Phase II Dose (RP2D) [Срок оценки: Observation is expected to continue through Cycle 6 Day 28 throughout the study, around 6 months.]
• Adverse Events (AEs) [Срок оценки: From the time of first dose of TQB3126 to 28 days after the last dose or until the start of other anti-tumor therapy, whichever occurs first.]
• Serious Adverse Events (SAEs) [Срок оценки: From the time of first dose of TQB3126 to 28 days after the last dose or until the start of other anti-tumor therapy, whichever occurs first.]
• Abnormal Incidence of Laboratory Test Indicators [Срок оценки: From the time of first dose of TQB3126 to 28 days after the last dose or until the start of other anti-tumor therapy, whichever occurs first.]
• Objective Response Rate (ORR) [Срок оценки: From the date of first dose until the date of first documented disease progression, assessed up to approximately 3 years.]

Вторичные конечные точки (12)

• Peak Concentration (Cmax) [Срок оценки: Escalation: pre-dose+0.5,1,2,3,4,6,8,12,24,48,72,120 hours post single dose (Cycle0); pre-dose Cycle1 Day1. Expansion/combo: pre-dose+0.5-12 hours Cycle1 Day1; 24 hours Day2. All: pre-dose Day 7,14,21; pre-dose+0.5-12 hours Day 28; pre-dose Cycle2 Day1.]
• Time to Reach Maximum Plasma Concentration (Tmax) [Срок оценки: Escalation: pre-dose+0.5,1,2,3,4,6,8,12,24,48,72,120 hours post single dose (Cycle0); pre-dose Cycle1 Day1. Expansion/combo: pre-dose+0.5-12 hours Cycle1 Day1; 24 hours Day2. All: pre-dose Day 7,14,21; pre-dose+0.5-12 hours Day 28; pre-dose Cycle2 Day1.]
• Elimination Half-life (t1/2) [Срок оценки: Escalation: pre-dose+0.5,1,2,3,4,6,8,12,24,48,72,120 hours post single dose (Cycle0); pre-dose Cycle1 Day1. Expansion/combo: pre-dose+0.5-12 hours Cycle1 Day1; 24 hours Day2. All: pre-dose Day 7,14,21; pre-dose+0.5-12 hours Day 28; pre-dose Cycle2 Day1.]
• Area Under the Plasma Concentration-time Curve From Time Zero to Time t (AUC0-t) [Срок оценки: Escalation: pre-dose+0.5,1,2,3,4,6,8,12,24,48,72,120 hours post single dose (Cycle0); pre-dose Cycle1 Day1. Expansion/combo: pre-dose+0.5-12 hours Cycle1 Day1; 24 hours Day2. All: pre-dose Day 7,14,21; pre-dose+0.5-12 hours Day 28; pre-dose Cycle2 Day1.]
• Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) [Срок оценки: Escalation: pre-dose+0.5,1,2,3,4,6,8,12,24,48,72,120 hours post single dose (Cycle0); pre-dose Cycle1 Day1. Expansion/combo: pre-dose+0.5-12 hours Cycle1 Day1; 24 hours Day2. All: pre-dose Day 7,14,21; pre-dose+0.5-12 hours Day 28; pre-dose Cycle2 Day1.]
• Apparent Clearance (CL/F) [Срок оценки: Escalation: pre-dose+0.5,1,2,3,4,6,8,12,24,48,72,120 hours post single dose (Cycle0); pre-dose Cycle1 Day1. Expansion/combo: pre-dose+0.5-12 hours Cycle1 Day1; 24 hours Day2. All: pre-dose Day 7,14,21; pre-dose+0.5-12 hours Day 28; pre-dose Cycle2 Day1.]
• Apparent Volume of Distribution (Vz/F) [Срок оценки: Escalation: pre-dose+0.5,1,2,3,4,6,8,12,24,48,72,120 hours post single dose (Cycle0); pre-dose Cycle1 Day1. Expansion/combo: pre-dose+0.5-12 hours Cycle1 Day1; 24 hours Day2. All: pre-dose Day 7,14,21; pre-dose+0.5-12 hours Day 28; pre-dose Cycle2 Day1.]
• Clinical Benefit Rate (CBR) [Срок оценки: From the date of first dose until the date of first documented disease progression, assessed up to approximately 3 years.]
• Disease Control Rate (DCR) [Срок оценки: From the date of first dose until the date of first documented disease progression, assessed up to approximately 3 years.]
• Duration of Response (DOR) [Срок оценки: From the date of first dose until the date of first documented disease progression, assessed up to approximately 3 years.]
• Progression-Free Survival (PFS) [Срок оценки: From the date of first dose until the date of first documented disease progression, assessed up to approximately 3 years.]
• Time to Response (TTR) [Срок оценки: From the date of first dose until the date of first documented disease progression, assessed up to approximately 3 years.]

Критерии участия

Критерии включения

• Subjects voluntarily participate in this study, sign the informed consent form, and demonstrate good treatment compliance.
• Aged 18 to 75 years at the time of informed consent signature; Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1; estimated survival expectancy of more than 3 months.
• Histopathologically confirmed breast cancer.
• Documented disease progression confirmed by clinical or imaging evidence during or after the most recent prior systemic therapy prior to the first study drug administration.
• Have evaluable lesions per RECIST v1.1 criteria (measurable lesions; or bone-only metastases with at least one osteolytic or mixed lesion).
• Adequate tissue samples shall be provided at screening for gene mutation testing to clarify genetic status.
• Laboratory test results meet the criteria specified in the protocol (blood routine, liver and renal function, coagulation function, cardiac ultrasound Left Ventricular Ejection Fraction(LVEF) and other indicators are all within the protocol-specified ranges).
• Subjects of childbearing potential must agree to use effective contraceptive measures throughout the study and for 6 months after study completion (the same requirement applies to male subjects); serum or urine pregnancy test result is negative within 7 days prior to enrollment.

Критерии исключения

• Other malignant tumors within 5 years prior to first dose, except those cured by single surgical treatment with at least 5 years of disease-free survival, or cured differentiated thyroid cancer, cervical carcinoma in situ, non-melanoma skin cancer, or superficial bladder tumors.
• Conditions affecting intravenous access or blood sampling, or multiple factors affecting oral drug administration/absorption (e.g., inability to swallow, chronic diarrhea, intestinal obstruction).
• Unresolved toxicity from prior therapy of Grade >1 (CTCAE v6.0), except Grade 2 alopecia, Grade 2 anemia, clinically insignificant laboratory abnormalities, or hypothyroidism stable on hormone replacement therapy.
• Major surgery, significant traumatic injury within 4 weeks before first dose, anticipated need for major surgery during the study, or long-standing unhealed fracture.
• Any bleeding event of Grade >=3 within 4 weeks before first dose.
• Arterial/venous thrombotic events within 6 months before first dose (e.g., cerebrovascular accident, deep vein thrombosis, pulmonary embolism), excluding catheter-related or superficial venous thrombosis.
• Active viral hepatitis that is poorly controlled (Hepatitis B Virus (HBV)/Hepatitis C Virus (HCV)-infected subjects meeting protocol-specified criteria may be enrolled).
• Active syphilis infection requiring treatment.
• Active tuberculosis, idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced or radiation pneumonitis requiring treatment, or history of/current interstitial lung disease (ILD).
• History of psychotropic substance abuse unable to be discontinued, mental disorders, epilepsy requiring treatment, or severe psychiatric/neurological disease.
• Planned or prior allogeneic bone marrow or solid organ transplantation.
• Decompensated cirrhosis (Child-Pugh Class B or C) or history of hepatic encephalopathy.
• Significant cardiovascular disease, including New York Heart Association(NYHA) Class >II heart failure, clinically significant ventricular arrhythmia, unstable angina, myocardial infarction within 12 months, markedly prolonged QT interval corrected by Fridericia's formula (QTcF), or personal/family history of congenital long QT syndrome.
• Poorly controlled hypertension (resting systolic BP >=160 mmHg or diastolic BP >=100 mmHg on at least 2 measurements >=24 hours apart).
• Active or uncontrolled serious infection (Grade >=2).
• Renal failure requiring hemodialysis or peritoneal dialysis; or history of/current nephrotic syndrome (except cured) or chronic nephritis.
• History of immunodeficiency, including HIV infection or other acquired/congenital immunodeficiency diseases.
• Poorly controlled autoimmune disease requiring immunosuppressants or systemic corticosteroids for immunosuppression, continued within 7 days before first dose (except low-dose corticosteroids).
• Clinically significant endometrial abnormalities (including hyperplasia, dysfunctional uterine bleeding, etc.).
• Tumor-related conditions/treatments: anti-cancer therapy within 3 weeks before first dose or still within the drug's washout period; prior local radiotherapy not meeting protocol-specified interval or target lesion requirements; use of National Medical Products Administration (NMPA)-approved proprietary Chinese medicine with anti-tumor indications within 1 week before first dose; imaging showing tumor invasion of major vessels with risk of fatal hemorrhage; uncontrolled pleural effusion/ascites/moderate-or-greater pericardial effusion requiring repeated drainage; known leptomeningeal metastasis or uncontrolled brain metastasis symptoms; severe skeletal-related events due to bone metastases.
• Known hypersensitivity to the study drug or its excipients.
• Participation in and use of another investigational anti-tumor drug within 4 weeks before first dose.
• Any concomitant disease or condition that, in the investigator's judgment, seriously endangers subject safety or study compliance, or any other reason making the subject unsuitable for enrollment.

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 · 6 центров

• Sun Yat-sen Memorial Hospital, Sun Yat-sen University — Гуанчжоу
• Meizhou People's Hospital — Meizhou
• Zhongnan Hospital of Wuhan University — Ухань
• The Third Xiangya Hospital of Central South University — Чанша
• Sichuan Cancer Hospital — Чэнду
• Tianjin Medical University Cancer Institute & Hospital — Тяньцзинь

Идентификаторы

NCT: NCT07697443 · TQB3126-I/II-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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