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

B-Cell Malignancies Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05683717
• Other study ID #: TT01488CN02
• Status: Recruiting
• Phase: Phase 1
• Start date: March 30, 2023
• Est. completion date: October 30, 2028

Study information

• Verified date: November 2023
• Source: TransThera Sciences (Nanjing), Inc.
• Contact: Sun Caixia, PhD
• Phone: 025-58216298
• Email: clinicaltrial[@]transtherabio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 37
• Est. completion date: October 30, 2028
• Est. primary completion date: October 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• B-Cell Malignancies
• Neoplasms

Intervention

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

Locations

Country	Name	City	State
China	The First Affiliated Hospital with Nanjing Medical University	Nanjing	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
TransThera Sciences (Nanjing), Inc.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-Limiting Toxicity (DLT) of TT-01488	Safety and tolerability of TT-01488 as a single agent	Up to 28 days after first dose
Primary	Dose recommend for dose expansion (DRDE)	Safety and tolerability of TT-01488 as a single agent	3 years
Primary	Maximum Tolerated Dose (MTD), if reached, of TT-01488	Safety and tolerability of TT-01488 as a single agent	Up to 28 days after first dose
Secondary	Number of participants with treatment-related adverse events (AEs)	Safety and tolerability of TT-01488 as a single agent. AEs will be assessed per CTCAE v5.0 or 2018 IWCLL and may include, but is not limited to, clinically abnormal laboratory tests, physical exams, vital signs, electrocardiograms, and ECOG performance status.	3 years
Secondary	Area under the concentration time curve (AUC 0-t)	Pharmacokinetic (PK) profile of TT-01488 as a single agent	3 years
Secondary	Maximum plasma concentration (Cmax)	Pharmacokinetic (PK) profile of TT-01488 as a single agent	3 years
Secondary	Time to Maximum Plasma Concentration (Tmax)	Pharmacokinetic (PK) profile of TT-01488 as a single agent	3 years
Secondary	Half-life (T1/2)	Pharmacokinetic (PK) profile of TT-01488 as a single agent	3 years
Secondary	Mean Residence Time (MRT)	Pharmacokinetic (PK) profile of TT-01488 as a single agent	3 years
Secondary	Apparent volume of distribution associated with the terminal phase (Vz/F)	Pharmacokinetic (PK) profile of TT-01488 as a single agent	3 years
Secondary	Apparent clearance (CL/F)	Pharmacokinetic (PK) profile of TT-01488 as a single agent	3 years
Secondary	Objective Response Rate (ORR)	Preliminary efficacy profile of TT-01488 as a single agent	3 years
Secondary	Disease Control Rate (DCR)	Preliminary efficacy profile of TT-01488 as a single agent	3 years
Secondary	Duration of Response (DOR)	Preliminary efficacy profile of TT-01488 as a single agent	3 years
Secondary	Progression free survival (PFS)	Preliminary efficacy profile of TT-01488 as a single agent	3 years
Secondary	Overall survival (OS)	Preliminary efficacy profile of TT-01488 as a single agent	3 years