Sonrotoclax: Film-coated tablets administered once daily at a dose as specified in the treatment arm
Zanubrutinib: 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)
Obinutuzumab: Given as an intravenous infusion administered per label.
Study summary
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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Key Inclusion Criteria:
* Confirmed diagnosis of one of the following:
NHL Cohorts:
1. MZL i. R/R extranodal, splenic, or nodal MZL defined as disease that relapsed after, or was refractory to, at least one prior therapy ii. Active disease requiring treatment
2. FL i. R/R FL (Grade 1, 2 or 3a based on the WHO 2008 classification of tumors of hematopoietic and lymphoid tissue) and defined as disease that relapsed after, or was refractory to, at least 1 prior systemic therapy
3. DLBCL i. R/R DLBCL (including all subtypes of DLBCL) defined as disease that relapsed after, or was refractory to, at least two prior systemic therapies and has either progressed following or is not a candidate for autologous stem cell transplant (due to comorbidities or non-responsiveness to salvage chemotherapy)
4. Transformed indolent B-cell NHL i. Any lymphoma otherwise eligible for Part 1 that has transformed into a more aggressive lymphoma. Patients with transformation from CLL or SLL (Richter's transformation) are not eligible for Part 1
CLL/SLL Cohorts:
5. CLL/SLL diagnosis that meets the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria i. Disease characterized as Treatment Naive (TN) or R/R disease defined as disease that relapsed after, or was refractory to, at least 1 prior therapy ii. Requiring treatment as defined by history
MCL cohorts:
6. WHO-defined MCL i. R/R MCL defined as disease that relapsed after, or was refractory to, at least 1 prior systemic therapy; ii. Requiring treatment in the opinion of the investigator
WM cohorts:
g. WHO-defined WM (clinical and definitive histologic diagnosis) i. R/R disease defined as disease that relapsed after, or was refractory to, at least 1 prior therapy; ii. Meeting at least 1 criterion for treatment according to consensus panel criteria from the Seventh International Workshop on Waldenström's Macroglobulinemia (Dimopoulos et al 2014)
* Measurable disease by computed tomography (CT)/magnetic resonance imaging (MRI), defined as:
1. CLL: at least 1 lymph node \> 1.5 cm in longest diameter and measurable in 2 perpendicular dimensions or clonal lymphocytes measured by flow cytometry
2. DLBCL, FL, MZL, MCL, or SLL: at least 1 lymph node \> 1.5 cm in longest diameter OR 1 extranodal lesion \> 1.0 cm in the longest diameter, measurable in at least 2 perpendicular dimensions. For MZL, isolated splenomegaly is considered measurable for this study
3. WM: serum immunoglobulin (Ig) M level \> 0.5 g/dL
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
* Adequate organ function
* Adequate pancreatic function indicated by:
1. Serum amylase ≤ 1.5 x upper limit of normal (ULN)
2. Serum lipase ≤ 1.5 x ULN
Key Exclusion Criteria:
* Known current central nervous system involvement by lymphoma/leukemia
* Known plasma cell neoplasm, prolymphocytic leukemia, history of or currently suspected Richter's syndrome
* Prior therapy ≥ 2 months with or progression on a B-cell lymphoma-2 (Bcl-2) inhibitor
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Primary outcome measure(s)
Number of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) — Up to 30 days after the last dose of study drug, an average of 18 months
Number of Participants Experiencing Serious Adverse Events (SAEs) — 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 — 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 — Up to approximately 2 months
Part 1, Part 3, Part 5: RP2D of Sonrotoclax — 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 — 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 — Up to approximately 2 months
Trial sites (43)
Facility
City
Region
Status
UCLA Hematologyoncology
Los Angeles
California
Northwestern University
Chicago
Illinois
University of Kansas Medical Center Research Institute
Kansas City
Kansas
Massachusetts General Hospital
Boston
Massachusetts
Mayo Clinic Rochester
Rochester
Minnesota
University of Nebraska Medical Center
Omaha
Nebraska
John Theurer Cancer Center Hackensack University Medical Center
Hackensack
New Jersey
Columbia University Medical Center
New York
New York
Memorial Sloan Kettering Cancer Center Mskcc
New York
New York
The James Cancer Hospital and Solove Research Institute At Ohio State University
Columbus
Ohio
Upmc Hillman Cancer Center(Univ of Pittsburgh)
Pittsburgh
Pennsylvania
Md Anderson Cancer Center
Houston
Texas
Fred Hutchinson Cancer Research Center
Seattle
Washington
Concord Repatriation General Hospital
Concord
New South Wales
Orange Health Service (Central West Cancer Care Centre)
Orange
New South Wales
Pindara Private Hospital
Benowa
Queensland
John Flynn Private Hospital
Tugun
Queensland
Royal Adelaide Hospital
Adelaide
South Australia
Flinders Medical Centre
Bedford PK
South Australia
Box Hill Hospital
Box Hill
Victoria
Monash Health
Clayton
Victoria
St Vincents Hospital Melbourne
Fitzroy
Victoria
Peter Maccallum Cancer Centre
Melbourne
Victoria
The Alfred Hospital
Melbourne
Victoria
Linear Clinical Research
Nedlands
Western Australia
Universitatsklinikum Carl Gustav Carus An Der Technischen Universitat Dresden
Dresden
Germany
Ospedale San Raffaele
Milan
Italy
Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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