AS-1763 in Patients With Previously Treated CLL/SLL or Non-Hodgkin Lymphoma

• Status: Not yet recruiting
• Trial end date: 2028-01-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Carna Biosciences, Inc.

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

• Absolute neutrophil count ≥0.75 × 10⁹/L

• Platelet count ≥50 × 10⁹/L

• Hemoglobin ≥8 g/dL

• Adequate hepatic function

• Adequate renal 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

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 National Cancer Institute - Common Terminology Criteria for Adverse Events (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