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

Summary

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

Eligibility

Inclusion 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

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 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

Conditions9

Locations13 sites

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