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

NCT05275504 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: TT01488US01
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 2

Brief Summary

This is a first-in-human (FIH), 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.

Conditions

B-Cell Malignancies

Keywords

B-Cell Malignancies; Non-Hodgkin's Lymphomas (NHL); BTK inhibitor; C481S mutation

Outcome Measures

Primary Outcomes (3)

• Dose-Limiting Toxicity (DLT) of TT-01488

  Safety and tolerability of TT-01488 as a single agent

  Up to 28 days after first dose

• Dose recommend for dose expansion (DRDE)

  Safety and tolerability of TT-01488 as a single agent

  1 - 1.5 years

• 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 Outcomes (13)

• Number of participants with treatment-related adverse events (AEs)

  1 - 1.5 years

• Objective Response Rate (ORR)

  1 - 1.5 years

• Disease Control Rate (DCR)

  1 - 1.5 years

• Duration of Response (DOR)

  1 - 1.5 years

• Progression free survival (PFS)

  1 - 1.5 years

Study Arms (2)

Dose Escalation for TT-01488

EXPERIMENTAL

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.

Drug: TT-01488

Dose Expansion for TT-01488

EXPERIMENTAL

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.

Drug: TT-01488

Interventions

TT-01488 DRUG

TT-01488 tablet will be administered orally once daily per protocol defined schedule.

Dose Escalation for TT-01488; Dose Expansion for TT-01488

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women ≥ 18 years of age with histologically or cytologically confirmed R/R B-NHL, including but not limited to chronic lymphocytic leukemia/small lymphocytic leukemia (CLL/SLL), Waldenström macroglobulinemia (WM), follicular lymphoma (FL), marginal zone lymphoma (MZL), diffuse large-b-cell lymphomas (DLBCL), and transformed lymphoma who failed or are intolerant to ≥ 1 prior standard of care regimens.
• Notes:
• Patients with prior treatment of BTK inhibitors are eligible
• Patients with low grade lymphoma must be progressing and requiring treatment:
• Patients with CLL must have disease requiring treatment as specified in 2018 IWCLL Guidelines (Appendix 5)
• Patients with B-cell NHL must have measurable disease per 2014 Lugano Classification (Appendix 6)
• Patients with WM must have minimum serum immunoglobulin M (IgM) level of ≥ 2 times the upper limit of normal (ULN)
• Body weight ≥ 40 kg
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
• Adequate organ function, defined by the following laboratory parameters:
• Hematologic:
• Absolute neutrophil count (ANC) ≥ 750/ul, unless due to bone marrow involvement due to disease
• Platelets ≥ 50,000/ul without transfusion within 7 days
• Hemoglobin ≥ 80 mg/dl without transfusion within 7 days
• Coagulation:

You may not qualify if:

• 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)
• A life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of TT-01488, or put the study outcomes at undue risk
• 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 including left bundle branch block, 2nd degree AV block type II, 3rd degree block, bradycardia, and corrected QT interval using Fridericia's Formula (QTcF) \> 470 msec, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification
• 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
• Any immunotherapy, , radiotherapy (limited-field radiation for palliation within 7 days), or experimental therapy within 4 weeks, or 5-half lives for chemotherapy and small molecule agents (whichever is shorter), before first dose of study drug (corticosteroids for disease-related symptoms allowed but require 1-week washout before study drug administration)
• 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
• Concomitant use of prohibited medications(Section 6.4.2), including:
• Therapeutic doses of warfarin sodium (Coumadin®) or any other coumarin-derivative anticoagulants
• Medications with known risk to cause QT prolongation or Torsades de pointes
• Strong CYP3A inhibitors and inducers (must be discontinued for at least 14 days or 5 half-lives, whichever is longer, before study treatment)

Sponsors & Collaborators

• TransThera Sciences (Nanjing), Inc.: lead

Study Sites (2)

Gabrail Cancer Center

Canton, Ohio, 44718, United States

RECRUITING

The University of Texas MD Anderson Cancer Center (MDACC)

Houston, Texas, 77030, United States

NOT YET RECRUITING

Study Officials

• Nitin Jain, MD

  The University of Texas MD Anderson Cancer Center (MDACC)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Caixia Sun, PhD

CONTACT

025-58216298; clinicaltrial@transtherabio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 21, 2022
• First Posted: March 11, 2022
• Study Start: June 1, 2022
• Primary Completion: September 1, 2022
• Study Completion: April 1, 2023
• Last Updated: June 9, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)