Clinical Trial Evaluating the Efficacy and Safety of TQB3454 Tablets in Participants With Advanced Solid Tumors

Официальное название

Phase II Clinical Trial Evaluating the Efficacy and Safety of TQB3454 Tablets in Participants With Advanced Solid Tumors

Обзор

This is a multicenter phase II study designed to evaluate the efficacy and safety of TQB3454 as monotherapy in patients with advanced solid tumors, divided into three cohorts.Cohort 1: Enrolled patients with diffuse glioma harbouring IDH1 R132 mutations. Cohort 2: Enrolled patients with advanced solid tumours (excluding glioma) harbouring IDH1 R132 mutations who failed standard therapy. Cohort 3: Enrolled patients with locally advanced, recurrent and/or metastatic biliary tract cancer without IDH1 mutations who progressed after gemcitabine or fluoropyrimidine-based treatment.

Вмешательства

• Препарат TQB3454 tablets
  TQB3454 is a selective inhibitor of the IDH1 mutant enzyme.

Первичные конечные точки

• Disease Control Rate (DCR) [Срок оценки: up to 48 weeks]

Вторичные конечные точки (9)

• Progression-free survival (PFS) [Срок оценки: up to 48 weeks]
• Secondary progression-free survival (PFS2) [Срок оценки: up to 48 weeks]
• The 6-month progression-free survival rate [Срок оценки: up to 6 months]
• Objective Response Rate(ORR) [Срок оценки: up to 48 weeks]
• Tumor Growth Rate (TGR) [Срок оценки: up to 48 weeks]
• Disease Remission Time (DOR) [Срок оценки: up to 48 weeks]
• Overall Survival (OS) [Срок оценки: up to 2 years]
• The 12-month overall survival rate [Срок оценки: up to 12 months]
• The incidence and severity of adverse event [Срок оценки: From the time when the participants signed the informed consent form until 30 days after the last medication administration / when they started a new anti-tumor treatment (whichever occurred first)，up to 48 weeks]

Критерии участия

Критерии включения

• Participants voluntarily joined this study and signed the informed consent form, showing good compliance;
• Age 18 years or above and 75 years or below (calculated based on the date of signing the informed consent form);
• Karnofsky Performance Status(KPS) score ≥ 60 points (for the first cohort), Eastern Cooperative Oncology Group(ECOG) score 0-1 point (for the second and third cohorts);
• Patients in Cohort 1 must have at least one radiographically measurable tumour lesion confirmed by magnetic resonance imaging (MRI) in two perpendicular dimensions per the Response Assessment in Neuro-Oncology (RANO) 2.0 criteria.Patients in Cohort 2 and Cohort 3 are required to have at least one measurable lesion in accordance with the Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST v1.1).
• Laboratory tests met the following criteria (within 14 days before screening, no blood transfusion, no use of hematopoietic stimulating drugs within 7 days for correction):

1\) Hemoglobin (HGB) ≥ 90 g/L; 2) Absolute neutrophil count (NEUT) ≥ 1.5×109/L; 3) Platelet count (PLT) ≥ 90×109/L; 4) Total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN); 5) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times ULN. If accompanied by liver metastasis, ALT and AST ≤ 5 times ULN; 6) Serum creatinine (CR) ≤ 1.5×ULN or creatinine clearance rate (CCR) ≥ 50 ml/min; 7) Prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR) ≤ 1.5×ULN (no anticoagulant treatment within 2 weeks previously); (6) Participants agreed to provide tumor tissue specimens obtained through surgery or biopsy, and cohort 1 and cohort 2 were confirmed to carry IDH1 R132 gene mutation by molecular testing; cohort 3 was confirmed not to carry IDH1 R132 gene mutation by molecular testing; (7) Glioma and other advanced solid tumors confirmed by histological or cytological examination;

For cohort 1 participants, they must meet:

• Diffuse glioma confirmed by histopathology (refer to the "WHO (Fifth Edition) Central Nervous System Tumor Classification"), and be patients with recurrence after surgery;
• The time from the last surgery to enrollment is greater than 4-6 weeks (including biopsy, surgical resection or other procedures entering the brain), and the surgical wound is judged to be healed well by the investigator;
• The dose of corticosteroid hormones was stable or gradually reduced within 5 days before administration;

For cohort 2 participants (excluding cholangiocarcinoma):

• Locally advanced progressive/metastatic solid tumors confirmed by tissue and/or cell pathology.
• Standard treatment failure or no standard treatment available.

For cohort 2 and cohort 3 participants with cholangiocarcinoma:

• Histologically or cytologically confirmed biliary tract cancer (BTC), including intrahepatic cholangiocarcinoma (iCCA; participants with mixed hepatocellular-cholangiocarcinoma where the cholangiocarcinoma component accounts for >50%), perihilar cholangiocarcinoma (pCCA), distal cholangiocarcinoma (dCCA), and gallbladder carcinoma (GBC), presenting as unresectable locally advanced, recurrent, and/or metastatic disease.
• Prior disease progression after gemcitabine- or fluoropyrimidine-based therapy. (8) Pregnant women of childbearing age should agree to use effective contraceptive measures during the study period and within 6 months after the study ends. Male participants should agree to use effective contraceptive measures during the study period and within 6 months after the study ends.

Критерии исключения

• Participants who have a history of other malignancies within 3 years prior to the first study drug administration, or who are concurrently diagnosed with other malignancies at screening.
• Presence of diseases interfering with intravenous infusion or venipuncture; or multiple factors impairing oral drug intake (e.g., inability to swallow, chronic diarrhea, intestinal obstruction, etc.).
• Adverse reactions from prior anticancer therapies that have not recovered to Grade ≤1 per CTCAE v6.0.
• Participants who received major surgical procedures or significant traumatic injuries within 4 weeks before the first dose, or those who are expected to undergo major surgery during the study treatment period (excluding surgeries specified in the protocol); or participants with unhealed wounds or fractures.
• Participants with any Grade ≥3 bleeding event(s) per CTCAE v6.0 within 4 weeks prior to the first study drug administration.
• History of arterial or venous thromboembolic events within 6 months before the first dose.
• Uncontrolled active viral hepatitis.
• Active syphilis infection requiring therapeutic intervention.
• Presence of active pulmonary tuberculosis, history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, radiation pneumonitis requiring treatment, or symptomatic active pneumonia.
• History of illicit psychotropic substance abuse with no successful abstinence, or diagnosed psychiatric disorders.
• Planned or prior allogeneic bone marrow transplantation or solid organ transplantation.
• Medical history of hepatic encephalopathy.
• Diagnosis of severe cardiovascular disease defined as any of the following:

New York Heart Association (NYHA) Class ≥II cardiac insufficiency, or echocardiography showing left ventricular ejection fraction (LVEF) <50%; History of clinically significant ventricular arrhythmias, or arrhythmias requiring long-term antiarrhythmic medication; Unstable angina pectoris; Myocardial infarction occurring within the past 12 months; Fridericia-corrected QT interval (QTcF) >450 milliseconds (msec) for male participants, >470 msec for female participants; Personal or family history of congenital long QT syndrome; History of deep vein thrombosis, pulmonary embolism, or any other severe thromboembolic event within 3 months prior to enrollment and first dosing; Current use or recent use (within 7 days before study treatment initiation) of aspirin (>325 mg/day, maximum antiplatelet dose), dipyridamole, ticlopidine, clopidogrel, or cilostazol.

• Active uncontrolled severe infection (Grade ≥2 infection per CTCAE v6.0).
• Renal failure requiring hemodialysis or peritoneal dialysis.
• History of immunodeficiency disorders, including HIV seropositivity or other acquired/congenital immunodeficiency diseases.
• Participants receiving immunosuppressive therapy, systemic hormones, or locally absorbable hormones for immunosuppressive purposes that must be continued within 7 days prior to the first dose (excluding glucocorticoids at a daily dose equivalent to <10 mg prednisone).
• Uncontrolled epilepsy.
• Tumor-related conditions and prior anticancer treatments:

Participants who received chemotherapy or immunotherapy within 3 weeks before the first dose, radiotherapy or small-molecule targeted therapy within 2 weeks before the first dose, or those still within 5 half-lives of prior anticancer agents (whichever duration is shorter). The washout period is calculated from the date of last prior treatment.

Received proprietary Chinese medicines with officially approved anti-tumor indications (per NMPA drug labeling) within 2 weeks prior to the first study drug administration.

Imaging (CT or MRI) confirms tumor invasion into major blood vessels; or the Investigator judges that the tumor is highly likely to invade critical blood vessels during study treatment and cause life-threatening massive hemorrhage.

Uncontrolled pleural effusion, pericardial effusion, or moderate to severe ascites requiring repeated drainage (as assessed by the Investigator).

Known spinal cord compression, leptomeningeal carcinomatosis, symptomatic brain metastases, or brain metastasis symptoms controlled for less than 4 weeks.

• Known hypersensitivity to any excipient component of the investigational product.
• Prior treatment with an IDH1 mutant inhibitor.
• Participation in another clinical trial involving investigational anti-tumor drugs within 4 weeks before the first study drug administration.
• Any condition judged by the Investigator to pose significant safety risks to the participant or interfere with the participant's ability to complete the study.

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 · 22 центра

• Sanbo Brain Hospital,Capital Medical University — Пекин
• Xuanwu Hospital Capital Medical University — Пекин
• Beijing Tiantan Hospital, Capital Medical University — Пекин
• Beijing Cancer Hospital — Пекин
• Peking University People's Hospital — Пекин
• The Second Hospital & Clinical Medical School, Lanzhou University — Lanzhou
• Sun Yat-Sen Uuniversity Cancer Cerntr — Гуанчжоу
• AnYang Tumor Hospital — Anyang
• … и ещё 14 центров

Идентификаторы

NCT: NCT07738679 · TQB3454-II-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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