Clinical Trial 22263

• Overview

  Study Title:

  A Phase 1b Study of Oral AS-1763 in Patients with Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma or B-cell Non-Hodgkin Lymphoma

  Summary:

  This is an open-label, multi-center Phase 1b clinical study of oral AS-1763 in patients with CLL/SLL or B-cell NHL who have failed or are intolerant to ≥2 lines of systemic therapy.

  Objective:

  Primary Objective: To determine the MTD and DLTs in patients with previously treated CLL/SLL or B-cell NHL. Secondary Objective(s): To evaluate the safety profile and tolerability of AS-1763 in patients with previously treated CLL/SLL or B-cell NHL. To evaluate the plasma PK of AS-1763. To assess the preliminary anti-tumor activity of AS-1763 based on ORR according to iwCLL 2018 for CLL, IWWM6 for WM, Lugano Treatment Response Criteria for MCL, MZL, SLL, FL, and other B-cell NHL, or other criteria as appropriate to tumor type, as assessed by the investigator.

• Treatments

  Therapies:

  Therapy (NOS)

  Medications:

  AS-1763 ()

• Inclusion Criteria

  Inclusion Criteria:
  • Age ≥18 years
  • Provided written informed consent
  • Histologically confirmed B-cell malignancy, including CLL/SLL, WM, MCL, MZL, or FL. Patients must have failed or are intolerant to ≥2 prior lines of systemic therapy
  • ECOG Performance Status 0 to 2
  • Adequate organ function
  • Ability to swallow tablets and comply with study requirements for the duration of study participation.
  • Male and female patients of reproductive potential: Willing to observe conventional and effective birth control methods
  • Other criteria apply

• Exclusion Criteria

  Exclusion Criteria:
  • Transformed disease (eg, Richter's transformation) prior to or during Screening
  • Investigational agent or anticancer therapy within 5 half-lives before the planned start of AS-1763, except therapeutic monoclonal antibody treatment which must be discontinued at least 4 weeks before the start of AS-1763. Current treatment with investigational therapy or planned investigational therapy which would be concurrent with this study.
  • Requiring therapeutic anticoagulation with warfarin.
  • Current treatment with certain strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers
  • Treatment with proton pump inhibitors within 7 days before first dose of AS-1763
  • Current treatment with strong P-glycoprotein inhibitors or strong breast cancer resistance protein (BCRP) inhibitors.
  • Refractory to transfusion support.
  • Major surgery within 4 weeks before planned start of AS-1763.
  • Radiotherapy with a limited field of radiation for palliation within 7 days of the first dose of study treatment
  • Any unresolved toxicities from prior therapy greater than NCI CTCAE Version 5.0 Grade 2 at the time of starting study treatment except for alopecia.
  • History of allogeneic or autologous stem cell transplant or chimeric antigen receptor T-cell (CAR-T) therapy within the last 30 days.
  • Active second malignancy unless in remission with life expectancy >2 years
  • Known central nervous system (CNS) involvement by systemic lymphoma. Patients with previous treatment for CNS involvement who are neurologically stable and without evidence of disease may be eligible if a compelling clinical rationale is provided by the investigator and with documented Sponsor approval.
  • Active uncontrolled autoimmune cytopenia (eg, autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura) where new therapy introduced or concomitant therapy escalated within the 4 weeks before study enrollment is required to maintain adequate blood counts.
  • Clinically significant, uncontrolled cardiac, cardiovascular disease or history of myocardial infarction within 6 months before planned start of AS-1763, or prolongation of the QT interval corrected for heart rate using Fridericia's Formula (QTcF) >470 msec on at least 2 of 3 consecutive ECGs, and mean QTcF >470 msec on all 3 ECGs, during Screening.
  • Active uncontrolled systemic bacterial, viral, fungal, or parasitic infection
  • Positive for human immunodeficiency virus (HIV). For patients with unknown HIV status, HIV testing will be performed at Screening.
  • Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal absorption of AS-1763
  • Pregnant or lactating.
  • Known hypersensitivity to any component or excipient of AS-1763.
  • Prior treatment with AS-1763 or other noncovalent BTKi such as pirtobrutinib or nemtabrutinib
  • Other exclusions may apply

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