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

Open to people ages 18 years and up

• Age ≥18 years
• Provided written informed consent
• Histologically confirmed B-cell malignancy, including CLL/SLL, WM, MCL, MZL, or FL.
• Patients with SLL, MCL, MZL, and FL: at least 1 radiographically measurable lesion
• Failed or are intolerant to ≥2 prior lines of systemic therapy
• ECOG Performance Status 0 to 2
• Adequate hematologic status (ie, absolute neutrophil count ≥0.75 × 10⁹/L, platelet count ≥50 × 10⁹/L, hemoglobin ≥8 g/dL) not requiring transfusion support or growth factors
• 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
• Male patients: agree not to donate sperm during and for 6 months after the study
• Dose Expansion Cohort 3 patients: prior treatment with pirtobrutinib (Jaypirca) for an approved indication

• 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 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 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 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.
• 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 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
• Dose Escalation and Cohort 3 patients: prior treatment with noncovalent BTKi except pirtobrutinib (Jaypirca)
• Dose Expansion Cohort 1 and Cohort 2 patients: prior treatment with any noncovalent BTKi