Mature B-Cell Malignancies
Conditions
Keywords
NHL, BCL2 Inhibitor, CLL, MCL, MZL, SLL, WM, Bcl-2i, BTKi
Brief 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.
Detailed description
Our company, previously known as BeiGene, is now officially BeOne Medicines. Because some of our older studies were sponsored under the name BeiGene, you may see both names used for this study on this website.
Interventions
DRUGSonrotoclax
Film-coated tablets administered once daily at a dose as specified in the treatment arm
DRUGZanubrutinib
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)
DRUGObinutuzumab
Given as an intravenous infusion administered per label.
Sponsors
BeOne Medicines
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) After a Single Dose of Sonrotoclax | 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 | Predose up to 12 hours postdose | — |
| Area Under the Concentration-Time Curve from Time 0 to Infinity (AUC0-∞) After a Single Dose of Sonrotoclax | Predose up to 12 hours postdose | — |
| Time Taken for Half the Initial Dose Administered to Be Eliminated from The Body (T1/2) of Sonrotoclax | Predose up to 12 hours postdose | — |
| Time to Maximum Plasma Concentration (Tmax) After a Single Dose of Sonrotoclax | Predose up to 12 hours postdose | — |
| Apparent Clearance (CL/F) After a Single Dose of Sonrotoclax | Predose up to 12 hours postdose | — |
| Apparent volume of distribution (Vz/F) After a Single Dose of Sonrotoclax | Predose up to 12 hours postdose | — |
| Steady State Area Under the Concentration-Time Curve of 0 - Last Day (AUCLast, ss) of Sonrotoclax | 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 | Predose up to 12 hours postdose | — |
| Steady State Maximum Observed Plasma Concentration (Cmax, ss) of Sonrotoclax | Predose up to 12 hours postdose | — |
| Part 3, Part 4: Steady State Maximum Observed Plasma Concentration (Cmax, ss) of zanubrutinib | Predose up to 12 hours postdose | — |
| Steady State Trough Observed Plasma Concentration (Ctrough, ss) of Sonrotoclax | Predose up to 12 hours postdose | — |
| Part 3, Part 4: Steady State Trough Observed Plasma Concentration (Ctrough, ss) of zanubrutinib | Predose up to 12 hours postdose | — |
| Steady State Time to Maximum Plasma Concentration (Tmax, ss) of Sonrotoclax | Predose up to 12 hours postdose | — |
| Part 3, Part 4: Steady State Time to Maximum Plasma Concentration (Tmax, ss) of zanubrutinib | Predose up to 12 hours postdose | — |
| Part 2: AUC of Sonrotoclax administered after a high fat/calorie meal (HF-Fed) | Predose up to 12 hours postdose | — |
| Part 2: Cmax of Sonrotoclax administered after a high fat/calorie meal (HF-Fed) | Predose up to 12 hours postdose | — |
| Part 2, Part 4, Part 6: Overall Response Rate (ORR) as Assessed by the Investigator | Up to 18 months | ORR is defined as the proportion of participants who had confirmed complete response Complete Response (CR) or Partial Response (PR) |
| Part 2: Major Response Rate (MRR) for WM as Assessed by the Investigator | Up to 18 months | — |
| Part 6: Minimum residual disease (MRD) negativity as measured by next generation sequencing | Up to 18 months | — |
Countries
Australia, Germany, Italy, New Zealand, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORStudy Director
BeOne Medicines
Outcome results
None listed