Active, not recruiting
Phase 1
Study of Bcl-2 Inhibitor Sonrotoclax (BGB-11417) in Participants With Mature B-Cell Malignancies
Condition(s) studied
Mature B-Cell Malignancies
Investigational drug(s) / intervention(s)
SonrotoclaxZanubrutinibObinutuzumab
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
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 |
Milan |
Italy |
|
| Ospedale Santa Maria Della Misericordia |
Perugia |
Italy |
|
| Azienda Unita Sanitaria Locale Di Ravenna |
Ravenna |
Italy |
|
| Fondazione Policlinico Universitario Agostino Gemelli |
Roma |
Italy |
|
| Centroricerche Cliniche Di Verona Srl |
Verona |
Italy |
|
| North Shore Hospital |
Auckland |
New Zealand |
|
| Auckland City Hospital |
Auckland |
New Zealand |
|
| Wellington Regional Hospital (Ccdhb) |
Wellington |
New Zealand |
|
| Vall D Hebron Institute of Oncology Vhio |
Barcelona |
Spain |
|
| Hospital Clinic de Barcelona |
Barcelona |
Spain |
|
| Hospital de La Santa Creu I Sant Pau |
Barcelona |
Spain |
|
| Ico H Duran I Reynals |
Barcelona |
Spain |
|
| Start Madrid Fundacion Jimenez Diaz |
Madrid |
Spain |
|
+ 3 more sites — see the full list on the official registry below.
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