Study of Bcl-2 Inhibitor Sonrotoclax (BGB-11417) in Participants With Mature B-Cell Malignancies
- Conditions
- Mature B-Cell Malignancies
- Interventions
- Registration Number
- NCT04277637
- Lead Sponsor
- BeiGene
- 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
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 437
- Confirmed diagnosis of one of the following:
NHL Cohorts:
-
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
-
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
-
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)
-
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:
-
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:
-
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:
- 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
- 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
- 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:
- Serum amylase ≤ 1.5 x upper limit of normal (ULN)
- Serum lipase ≤ 1.5 x ULN
Key
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Sonrotoclax Monotherapy Dose Finding: Part 1 Sonrotoclax Participants with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) including follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), marginal zone lymphoma (MZL) or transformed NHL, mantle cell lymphoma (MCL); Waldenströms macroglobulinemia (WM); and chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) will receive oral sonrotoclax evaluated as monotherapy. Sonrotoclax + Zanubrutinib Combination Therapy Dose Finding: Part 3 Zanubrutinib Participants with R/R MCL, R/R or treatment-naïve (TN) CLL/SLL will receive oral sonrotoclax in combination with zanubrutinib. Sonrotoclax + Zanubrutinib Combination Therapy Dose Expansion: Part 4 Zanubrutinib Participants with R/R indolent NHL including FL, MZL; aggressive NHL including DLBCL, transformed NHL; R/R MCL; R/R or treatment-naïve (TN) CLL/SLL will receive oral sonrotoclax in combination with zanubrutinib at an RP2D dose to further define the safety profile. Sonrotoclax + Zanubrutinib Combination Therapy Dose Escalation: Part 5 Sonrotoclax Participants with treatment naïve CLL/SLL will receive oral sonrotoclax in combination with obinutuzumab without and with zanubrutinib. Sonrotoclax + Zanubrutinib Combination Therapy Dose Escalation: Part 5 Zanubrutinib Participants with treatment naïve CLL/SLL will receive oral sonrotoclax in combination with obinutuzumab without and with zanubrutinib. Sonrotoclax + Zanubrutinib Combination Therapy Dose Escalation: Part 5 Obinutuzumab Participants with treatment naïve CLL/SLL will receive oral sonrotoclax in combination with obinutuzumab without and with zanubrutinib. Sonrotoclax + Zanubrutinib Combination Therapy Dose Expansion: Part 6 Zanubrutinib Participants with treatment naïve CLL/SLL will receive oral sonrotoclax in combination with obinutuzumab without and with zanubrutinib at an RP2D dose to further define the safety profile. Sonrotoclax + Zanubrutinib Combination Therapy Dose Expansion: Part 6 Obinutuzumab Participants with treatment naïve CLL/SLL will receive oral sonrotoclax in combination with obinutuzumab without and with zanubrutinib at an RP2D dose to further define the safety profile. Sonrotoclax Monotherapy Expansion Cohorts: Part 2 Sonrotoclax Participants with R/R indolent NHL including FL, MZL; aggressive NHL including DLBCL, transformed NHL; CLL/SLL with low tumor burden or low creatine clearance; CLL/SLL with without high tumor burden or low creatine clearance will receive oral sonrotoclax at the RP2D dose to further define the safety profile. Sonrotoclax + Zanubrutinib Combination Therapy Dose Finding: Part 3 Sonrotoclax Participants with R/R MCL, R/R or treatment-naïve (TN) CLL/SLL will receive oral sonrotoclax in combination with zanubrutinib. Sonrotoclax + Zanubrutinib Combination Therapy Dose Expansion: Part 4 Sonrotoclax Participants with R/R indolent NHL including FL, MZL; aggressive NHL including DLBCL, transformed NHL; R/R MCL; R/R or treatment-naïve (TN) CLL/SLL will receive oral sonrotoclax in combination with zanubrutinib at an RP2D dose to further define the safety profile. Sonrotoclax + Zanubrutinib Combination Therapy Dose Expansion: Part 6 Sonrotoclax Participants with treatment naïve CLL/SLL will receive oral sonrotoclax in combination with obinutuzumab without and with zanubrutinib at an RP2D dose to further define the safety profile.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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
Trial Locations
- Locations (44)
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
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