The purpose of this study is to determine the safety, tolerability; and to define the maximum tolerated dose (MTD) and Recommended Phase 2 Dose (RP2D); and to evaluate the safety and tolerability of the ramp-up dosing schedule and at the RP2D of BGB-11417 monotherapy, and when given in combination with zanubrutinib and obinutuzumab.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
437
Film-coated tablets administered once daily at a dose as specified in the treatment arm
320 mg daily administered as two 80-mg capsules twice a day (160 mg twice a day) or as four 80-mg capsules once a day (320 mg once a day)
Given as an intravenous infusion administered per label.
Number of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)
Time frame: Up to 30 days after the last dose of study drug, an average of 18 months
Number of Participants Experiencing Serious Adverse Events (SAEs)
Time frame: Up to 30 days after the last dose of study drug, an average of 18 months
Number of Participants Experiencing Adverse Events (AEs) leading to discontinuation of Sonrotoclax
Time frame: Up to 30 days after the last dose of study drug, an average of 18 months
Part 1, Part 3: Maximum Tolerated Dose (MTD) of Sonrotoclax
Time frame: Up to approximately 2 months
Part 1, Part 3, Part 5: RP2D of Sonrotoclax
Time frame: Day 1 to last dose of study drug, an average of 18 months
Part 1, Part 3, Part 5: Number of participants experiencing tumor lysis syndrome (TLS) relevant events
Time frame: Up to 30 days after the last dose of study drug, an average of 18 months
Part 1, Part 3, Part 5: Number of Participants Experiencing Dose-Limiting Toxicities (DLTs
Time frame: Up to approximately 2 months
Maximum Observed Plasma Concentration (Cmax) After a Single Dose of Sonrotoclax
Time frame: Predose up to 12 hours postdose
Area Under the Concentration-Time Curve from Time 0 to the Last Quantifiable Concentration (AUC0-last) After a Single Dose of Sonrotoclax
Time frame: Predose up to 12 hours postdose
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UCLA Hematologyoncology
Los Angeles, California, United States
Northwestern University
Chicago, Illinois, United States
University of Kansas Medical Center Research Institute
Kansas City, Kansas, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Mayo Clinic Rochester
Rochester, Minnesota, United States
University of Nebraska Medical Center
Omaha, Nebraska, United States
John Theurer Cancer Center Hackensack University Medical Center
Hackensack, New Jersey, United States
Columbia University Medical Center
New York, New York, United States
Memorial Sloan Kettering Cancer Center Mskcc
New York, New York, United States
The James Cancer Hospital and Solove Research Institute At Ohio State University
Columbus, Ohio, United States
...and 34 more locations
Area Under the Concentration-Time Curve from Time 0 to Infinity (AUC0-∞) After a Single Dose of Sonrotoclax
Time frame: Predose up to 12 hours postdose
Time Taken for Half the Initial Dose Administered to Be Eliminated from The Body (T1/2) of Sonrotoclax
Time frame: Predose up to 12 hours postdose
Time to Maximum Plasma Concentration (Tmax) After a Single Dose of Sonrotoclax
Time frame: Predose up to 12 hours postdose
Apparent Clearance (CL/F) After a Single Dose of Sonrotoclax
Time frame: Predose up to 12 hours postdose
Apparent volume of distribution (Vz/F) After a Single Dose of Sonrotoclax
Time frame: Predose up to 12 hours postdose
Steady State Area Under the Concentration-Time Curve of 0 - Last Day (AUCLast, ss) of Sonrotoclax
Time frame: Predose up to 12 hours postdose
Part 3, Part 4: Steady State Area Under the Concentration-Time Curve of 0 - Last Day (AUCLast, ss) of zanubrutinib
Time frame: Predose up to 12 hours postdose
Steady State Maximum Observed Plasma Concentration (Cmax, ss) of Sonrotoclax
Time frame: Predose up to 12 hours postdose
Part 3, Part 4: Steady State Maximum Observed Plasma Concentration (Cmax, ss) of zanubrutinib
Time frame: Predose up to 12 hours postdose
Steady State Trough Observed Plasma Concentration (Ctrough, ss) of Sonrotoclax
Time frame: Predose up to 12 hours postdose
Part 3, Part 4: Steady State Trough Observed Plasma Concentration (Ctrough, ss) of zanubrutinib
Time frame: Predose up to 12 hours postdose
Steady State Time to Maximum Plasma Concentration (Tmax, ss) of Sonrotoclax
Time frame: Predose up to 12 hours postdose
Part 3, Part 4: Steady State Time to Maximum Plasma Concentration (Tmax, ss) of zanubrutinib
Time frame: Predose up to 12 hours postdose
Part 2: AUC of Sonrotoclax administered after a high fat/calorie meal (HF-Fed)
Time frame: Predose up to 12 hours postdose
Part 2: Cmax of Sonrotoclax administered after a high fat/calorie meal (HF-Fed)
Time frame: Predose up to 12 hours postdose
Part 2, Part 4, Part 6: Overall Response Rate (ORR) as Assessed by the Investigator
ORR is defined as the proportion of participants who had confirmed complete response Complete Response (CR) or Partial Response (PR)
Time frame: Up to 18 months
Part 2: Major Response Rate (MRR) for WM as Assessed by the Investigator
Time frame: Up to 18 months
Part 6: Minimum residual disease (MRD) negativity as measured by next generation sequencing
Time frame: Up to 18 months