Clinical trial NCT05683717: A Phase 1 Study to Evaluate the Safety and Tolerability of TT-01488 in Patients With B-Cell Malignancies
Official title: A Phase I, Multicenter, Open Label, and Dose-Escalation Study of TT-01488, Administered Orally in Adult Patients With B-Cell Malignancies
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: B-Cell Malignancies
Lead sponsor: TransThera Sciences (Nanjing), Inc.
Sponsor class: INDUSTRY
First posted: 2023-01-13
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Dose-Limiting Toxicity (DLT) of TT-01488
timeFrame: Up to 28 days after first dose
measure: Dose recommend for dose expansion (DRDE)
timeFrame: 3 years
measure: Maximum Tolerated Dose (MTD), if reached, of TT-01488
timeFrame: Up to 28 days after first dose
Secondary outcomes:
measure: Number of participants with treatment-related adverse events (AEs)
timeFrame: 3 years
measure: Area under the concentration time curve (AUC 0-t)
timeFrame: 3 years
measure: Maximum plasma concentration (Cmax)
timeFrame: 3 years
measure: Time to Maximum Plasma Concentration (Tmax)
timeFrame: 3 years
measure: Half-life (T1/2)
timeFrame: 3 years
measure: Mean Residence Time (MRT)
timeFrame: 3 years
measure: Apparent volume of distribution associated with the terminal phase (Vz/F)
timeFrame: 3 years
measure: Apparent clearance (CL/F)
timeFrame: 3 years
measure: Objective Response Rate (ORR)
timeFrame: 3 years
measure: Disease Control Rate (DCR)
timeFrame: 3 years
measure: Duration of Response (DOR)
timeFrame: 3 years
measure: Progression free survival (PFS)
timeFrame: 3 years
measure: Overall survival (OS)
timeFrame: 3 years
Other outcomes:
Locations:
city: Nanjing
country: China
facility: The First Affiliated Hospital with Nanjing Medical University
state: Jiangsu
Study officials:
affiliation: The First Affiliated Hospital with Nanjing Medical University
name: Li Jianyong
role: PRINCIPAL_INVESTIGATOR
affiliation: The First Affiliated Hospital with Nanjing Medical University
name: Xu Wei
role: PRINCIPAL_INVESTIGATOR
References: