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.
This study consists of 2 parts. Dose escalation part will enroll up to 27 patients to evaluate safety profile and tolerance of docirbrutinib using 3+3 design. The starting dose of docirbrutinib in oral tablet form is 100 mg twice daily (200 mg/day). Dose escalation will continue up to the planned maximum dose level or until the maximum tolerated dose (MTD) has been identified. Dose expansion part will enroll up to 48 CLL/SLL patients (Cohort 1), up to 35 NHL patients (Cohort 2), and up to 10 patients with prior pirtobrutinib treatment for an approved indication (Cohort 3). The first 30 patients in each Cohort 1 or 2 will be allocated to three dose levels (n=10 at each dose level) which will be selected based on the data from dose escalation. Preliminary efficacy and safety data from the first 30 patients in one of cohorts will be used to identify the provisional recommended Phase 2 dose (RP2D) level. Thereafter, up to a further 18 patients for Cohort 1 and up to a further 5 patients for Cohort 2 will be enrolled and allocated to the provisional RP2D level. Cohort 3 will be enrolled in parallel with Cohorts 1 and 2 and will be allocated to up to two dose levels (either n=10 at a single dose level or n=5 at each of 2 dose levels). Study assessments will continue for 24 cycles (1 cycle = 28 days) or until disease progression, occurrence of unacceptable toxicity, or discontinuation because of other reasons. Patients will then be followed for survival status for a further 2 years. RP2D will be determined based on all the data generated in the study.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
120
oral tablet, twice daily
UC Irvine Health
Orange, California, United States
RECRUITINGMount Sinai Comprehensive Cancer Center
Miami Beach, Florida, United States
RECRUITINGMoffitt Cancer Center
Tampa, Florida, United States
RECRUITINGNorthwestern Memorial Hospital
Chicago, Illinois, United States
RECRUITINGAmerican Oncology Partners
Fort Wayne, Indiana, United States
RECRUITINGUniversity of Maryland Medical Center - Greenebaum Comprehensive Cancer Center
Baltimore, Maryland, United States
RECRUITINGUniversity of Massachusetts Memorial Medical Center
Worcester, Massachusetts, United States
RECRUITINGOptum Medical Care PC
Westbury, New York, United States
RECRUITINGDuke University
Durham, North Carolina, United States
RECRUITINGTaylor Cancer Research Center
Maumee, Ohio, United States
RECRUITING...and 3 more locations
Number of patients with dose limiting toxicities (DLTs) and determination of maximum tolerated dose (MTD)
Dose escalation
Time frame: Up to 24 cycles (1 cycle = 28 days)
Overall response rate (ORR) as assessed by investigator
Dose expansion
Time frame: Up to 24 cycles (1 cycle = 28 days)
Number of patients with adverse events (AEs) and clinical laboratory abnormalities
Dose escalation, dose expansion
Time frame: Up to 24 cycles (1 cycle = 28 days)
Area under the plasma concentration versus time curve (AUC) of docirbrutinib
Dose escalation, dose expansion
Time frame: Up to 24 cycles (1 cycle = 28 days)
Peak Plasma Concentration (Cmax) of docirbrutinib
Dose escalation, dose expansion
Time frame: Up to 24 cycles (1 cycle = 28 days)
Time to maximum plasma concentration (tmax) of docirbrutinib
Dose escalation, dose expansion
Time frame: Up to 24 cycles (1 cycle = 28 days)
ORR as assessed by investigator
Dose escalation
Time frame: Up to 24 cycles (1 cycle = 28 days)
Best overall response as assessed by investigator
Dose expansion
Time frame: Up to 24 cycles (1 cycle = 28 days)
Duration of response as assessed by investigator
Dose expansion
Time frame: Up to 24 cycles (1 cycle = 28 days)
Progression free survival as assessed by investigator
Dose expansion
Time frame: Up to 24 cycles (1 cycle = 28 days)
Overall survival
Dose expansion
Time frame: Up to 4 years
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