A Phase 1 Study to Evaluate the Safety and Tolerability of TT-01488 in Patients With B-Cell Malignancies

Официальное название

A Phase I, Multicenter, Open Label, and Dose-Escalation Study of TT-01488, Administered Orally in Adult Patients With B-Cell Malignancies

Обзор

This is a multicenter, open-label Phase I dose escalation study to evaluate the safety and preliminary efficacy of the TT-01488 tablet, a non-covalent reversible BTK inhibitor, for the treatment of adult patients with B-cell malignancies.

Подробное описание

The study will consist of two parts, dose escalation and dose expansion. A modified 3+3 design will be used to guide the dose escalation and the determination of the dose recommended for dose expansion (DRDE). A sentinel cohort comprising of one subject will be enrolled at a starting dose of 50 mg q.d. Subsequently, patients will be enrolled according to the standard 3+3 dose escalation design to determine the DRDE. Once the DRDE has been selected, TT-01488 of DRDE will be further tested in the dose expansion cohort to verify the safety and preliminary efficacy as observed in the dose escalation cohorts. A recommended Phase II dose (RP2D) may be determined based on the totality of safety, pharmacokinetics, and efficacy data from the dose escalation cohorts and dose expansion cohort.

Вмешательства

• Препарат TT-01488 Tablets
  TT-01488 tablet will be administered orally once daily per protocol defined schedule.

Первичные конечные точки

• Dose-Limiting Toxicity (DLT) of TT-01488 [Срок оценки: Up to 28 days after first dose]
• Dose recommend for dose expansion (DRDE) [Срок оценки: 3 years]
• Maximum Tolerated Dose (MTD), if reached, of TT-01488 [Срок оценки: Up to 28 days after first dose]

Вторичные конечные точки (12)

• Number of participants with treatment-related adverse events (AEs) [Срок оценки: 3 years]
• Area under the concentration time curve (AUC 0-t) [Срок оценки: 3 years]
• Maximum plasma concentration (Cmax) [Срок оценки: 3 years]
• Time to Maximum Plasma Concentration (Tmax) [Срок оценки: 3 years]
• Half-life (T1/2) [Срок оценки: 3 years]
• Mean Residence Time (MRT) [Срок оценки: 3 years]
• Apparent volume of distribution associated with the terminal phase (Vz/F) [Срок оценки: 3 years]
• Apparent clearance (CL/F) [Срок оценки: 3 years]
• Objective Response Rate (ORR) [Срок оценки: 3 years]
• Disease Control Rate (DCR) [Срок оценки: 3 years]
• Duration of Response (DOR) [Срок оценки: 3 years]
• Progression free survival (PFS) [Срок оценки: 3 years]

Критерии участия

Критерии включения

• Participants with histologically confirmed B-cell malignancy, failed or intolerant to either ≥ 2 prior standard/common regimens given in combination or sequentially OR have received 1 prior BTK-containing regimen, relapse/refractory, and with treatment indication:

• CLL/SLL treated with prior immunochemistry or BTK inhibitor containing regimen;
• DLBCL treated with prior CD20 or anthracyclines containing regimen;
• Other types of B-cell NHL treated with prior CD20 containing regimen
• Adequate organ function, defined by the following laboratory parameters:

• Hematologic:
• Absolute neutrophil count (ANC) ≥ 0.75×10\^9/L, and ≥ 0.5×10\^9/L if bone marrow involved
• Platelets ≥ 50×10\^9/L without transfusion within 7 days, and ≥ 30×10\^9/L if bone marrow involved
• Hemoglobin ≥ 8.0 g/dL without transfusion within 7 days, and ≥ 7.0 g/dL if bone marrow involved

• Coagulation:
• Prothrombin time (PT) ≤ 1.5 × ULN
• Activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN

• Renal function:
• Creatinine clearance ≥ 30 mL/min estimated glomerular filtration rate based on Cockcroft-Gault formula

• Liver function:
• Total bilirubin ≤ 1.5 × ULN (unless due to Gilbert's disease)
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.5 × ULN unless disease-related

Критерии исключения

• Women who are pregnant or lactating
• Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease-free for at least 2 years or which will not limit survival to < 2 years (Note: these cases must be discussed with the Medical Monitor and/or Investigator)
• Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or significant screening ECG abnormalities
• Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction
• History of allogeneic or autologous stem cell transplant (SCT) or chimeric antigen receptor-modified T-cell (CAR-T) therapy within the past 60 days or with any of the following:

• Active graft versus host disease (GvHD);
• Cytopenias from incomplete blood cell count recovery post-transplant;
• Need for anti-cytokine therapy for toxicity from CAR-T therapy; residual symptoms of neurotoxicity > Grade 1 from CAR-T therapy;
• Ongoing immunosuppressive therapy
• Grade ≥ 2 toxicity (other than alopecia) continuing from prior anticancer therapy, including radiation

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• The First Affiliated Hospital with Nanjing Medical University — Нанкин

Идентификаторы

NCT: NCT05683717 · TT01488CN02

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗