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

Eligibility Criteria

• * 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 docirbrutinib, except therapeutic monoclonal antibody treatment which must be discontinued at least 4 weeks before the start of docirbrutinib
• * 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 docirbrutinib
• * Current treatment with strong P-glycoprotein inhibitors or strong BCRP inhibitors
• * Refractory to transfusion support
• * Major surgery within 4 weeks before planned start of docirbrutinib
• * 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 docirbrutinib, 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 docirbrutinib
• * Pregnant or lactating.
• * Known hypersensitivity to any component or excipient of docirbrutinib
• * Prior treatment with docirbrutinib
• * 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