A Phase I, Multicenter, Open Label, and Dose-Escalation Study of TT-01488, Administered Orally in Adult Patients With B-Cell Malignancies
Overview
- Phase
- Phase 1
- Intervention
- TT-01488 Tablets
- Conditions
- B-Cell Malignancies
- Sponsor
- TransThera Sciences (Nanjing), Inc.
- Enrollment
- 37
- Locations
- 1
- Primary Endpoint
- Dose recommend for dose expansion (DRDE)
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
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.
Investigators
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:
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
Arms & Interventions
Dose Escalation for TT-01488
TT-01488 tablets will be administered once daily in a 28-day cycle in increasing strength in order to determine the recommended dose for dose expansion.
Intervention: TT-01488 Tablets
Dose Expansion for TT-01488
TT-01488 tablets will be administered once daily in 28-day cycles to verify the safety and preliminary efficacy as observed in the dose escalation cohorts.
Intervention: TT-01488 Tablets
Outcomes
Primary Outcomes
Dose recommend for dose expansion (DRDE)
Time Frame: 3 years
Safety and tolerability of TT-01488 as a single agent
Dose-Limiting Toxicity (DLT) of TT-01488
Time Frame: Up to 28 days after first dose
Safety and tolerability of TT-01488 as a single agent
Maximum Tolerated Dose (MTD), if reached, of TT-01488
Time Frame: Up to 28 days after first dose
Safety and tolerability of TT-01488 as a single agent
Secondary Outcomes
- Area under the concentration time curve (AUC 0-t)(3 years)
- Apparent volume of distribution associated with the terminal phase (Vz/F)(3 years)
- Apparent clearance (CL/F)(3 years)
- Half-life (T1/2)(3 years)
- Mean Residence Time (MRT)(3 years)
- Objective Response Rate (ORR)(3 years)
- Duration of Response (DOR)(3 years)
- Progression free survival (PFS)(3 years)
- Overall survival (OS)(3 years)
- Maximum plasma concentration (Cmax)(3 years)
- Time to Maximum Plasma Concentration (Tmax)(3 years)
- Disease Control Rate (DCR)(3 years)
- Number of participants with treatment-related adverse events (AEs)(3 years)