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

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.

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 regimenAdequate organ function, defined by the following laboratory parameters:Hematologic:Absolute neutrophil count (ANC) ≥ 0.75×10^9/L, unless due to bone marrow involvement due to diseasePlatelets ≥ 50×10^9/L without transfusion within 7 daysHemoglobin ≥ 8.0 g/dl without transfusion within 7 daysCoagulation:Prothrombin time (PT) ≤ 1.5 × ULNActivated partial thromboplastin time (aPTT) ≤ 1.5 × ULNRenal function:Creatinine clearance ≥ 30 mL/min estimated glomerular filtration rate based on Cockcroft-Gault formulaLiver function:Total bilirubin ≤ 1.5 × ULN (unless due to Gilbert's disease)Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.5 × ULN unless disease-relatedExclusion Criteria:Women who are pregnant or lactatingPrior 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 abnormalitiesMalabsorption 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 obstructionHistory 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 therapyGrade ≥ 2 toxicity (other than alopecia) continuing from prior anticancer therapy, including radiation