Evaluating TT-01488 for treating B-cell malignancies

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

This study is testing a new drug called TT-01488 to see if it can safely help adults with B-cell cancers.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 37 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: TransThera Sciences (Nanjing), Inc. (industry)
• Drugs / interventions: CAR-T, chimeric antigen receptor, radiation
• Locations: 1 site (Nanjing, Jiangsu)
• Trial ID: NCT05683717 on ClinicalTrials.gov

What this trial studies

This multicenter, open-label Phase I study aims to assess the safety and preliminary efficacy of TT-01488, a non-covalent reversible BTK inhibitor, in adult patients with B-cell malignancies. The study will follow a dose escalation and expansion design, starting with a sentinel cohort at a dose of 50 mg daily. Subsequent patients will be enrolled using a modified 3+3 design to determine the recommended dose for further testing. The study will ultimately evaluate the safety and efficacy of the selected dose in a larger cohort.

Who should consider this trial

Good fit: Ideal candidates are adults with histologically confirmed B-cell malignancies who have failed or are intolerant to multiple prior treatments.

Not a fit: Patients with untreated B-cell malignancies or those who have not received prior therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with B-cell malignancies who have limited treatment alternatives.

How similar studies have performed: Other studies involving BTK inhibitors have shown promise in treating B-cell malignancies, suggesting potential for success with this approach.

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

Where this trial is running

Nanjing, Jiangsu

• The First Affiliated Hospital with Nanjing Medical University — Nanjing, Jiangsu, China (RECRUITING)

Study contacts

• Principal investigator: Li Jianyong — The First Affiliated Hospital with Nanjing Medical University
• Study coordinator: Sun Caixia, PhD

Conditions: B-Cell Malignancies