Study of Bcl-2 Inhibitor Sonrotoclax (BGB-11417) in Participants With Mature B-Cell Malignancies

A Phase 1a/1b Open-Label Dose Escalation and Expansion Study of Bcl-2 Inhibitor BGB-11417 in Patients With Mature B-Cell Malignancies

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 Overview

• Status: Active, not recruiting
• Conditions: Mature B-Cell Malignancies
• Intervention / Treatment: Drug: Zanubrutinib; Drug: Sonrotoclax; Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 437
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Concord, New South Wales, Australia, NSW 2139
      • Concord Repatriation General Hospital
    • Orange, New South Wales, Australia, NSW 2800
      • Orange Health Service (Central West Cancer Care Centre)
  • Queensland
    • Benowa, Queensland, Australia, QLD 4217
      • Pindara Private Hospital
    • Tugun, Queensland, Australia, QLD 4224
      • John Flynn Private Hospital
  • South Australia
    • Adelaide, South Australia, Australia, SA 5000
      • Royal Adelaide Hospital
    • Bedford PK, South Australia, Australia, SA 5042
      • Flinders Medical Centre
  • Victoria
    • Box Hill, Victoria, Australia, VIC 3128
      • Box Hill Hospital
    • Clayton, Victoria, Australia, VIC 3168
      • Monash Health
    • Fitzroy, Victoria, Australia, VIC 3065
      • St Vincents Hospital Melbourne
    • Melbourne, Victoria, Australia, VIC 3000
      • Peter Maccallum Cancer Centre
    • Melbourne, Victoria, Australia, VIC 3004
      • The Alfred Hospital
  • Western Australia
    • Nedlands, Western Australia, Australia, WA 6009
      • Linear Clinical Research
• Germany
  • Dresden, Germany, 01307
    • Universitatsklinikum Carl Gustav Carus An Der Technischen Universitat Dresden
• Italy
  • Milan, Italy, 20132
    • Ospedale San Raffaele
  • Milan, Italy, 20162
    • Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
  • Perugia, Italy, 6129
    • Ospedale Santa Maria Della Misericordia
  • Ravenna, Italy, 48121
    • Azienda Unita Sanitaria Locale Di Ravenna
  • Roma, Italy, 00168
    • Fondazione Policlinico Universitario Agostino Gemelli
  • Verona, Italy, 37134
    • Centroricerche Cliniche Di Verona Srl
• New Zealand
  • Auckland, New Zealand, 1023
    • Auckland City Hospital
  • Auckland, New Zealand, 0622
    • North Shore Hospital
  • Wellington, New Zealand, 6021
    • Wellington Regional Hospital (Ccdhb)
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic De Barcelona
  • Barcelona, Spain, 08041
    • Hospital De La Santa Creu I Sant Pau
  • Barcelona, Spain, 08907
    • Ico H Duran I Reynals
  • Barcelona, Spain, 08035
    • Vall D Hebron Institute of Oncology Vhio
  • Madrid, Spain, 28040
    • Start Madrid Fundacion Jimenez Diaz
  • Salamanca, Spain, 37007
    • Hospital Universitario de Salamanca
  • Santander, Spain, 39008
    • Hospital Universitario Marqués de Valdecilla
• United Kingdom
  • Leeds, United Kingdom, LS9 7TF
    • The Leeds Teaching Hospitals Nhs Trust
• United States
  • California
    • Los Angeles, California, United States, 90095-3075
      • UCLA Hematologyoncology
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Kansas
    • Kansas City, Kansas, United States, 66160-8500
      • University of Kansas Medical Center Research Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905-0001
      • Mayo Clinic Rochester
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center Hackensack University Medical Center
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10065-6800
      • Memorial Sloan Kettering Cancer Center Mskcc
  • Ohio
    • Columbus, Ohio, United States, 43210-1240
      • The James Cancer Hospital and Solove Research Institute At Ohio State University
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232-1309
      • Upmc Hillman Cancer Center(Univ of Pittsburgh)
  • Texas
    • Houston, Texas, United States, 77030-3907
      • MD Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109-4433
      • Fred Hutchinson Cancer Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sonrotoclax Monotherapy Dose Finding: Part 1; 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.	Drug: Sonrotoclax; Film-coated tablets administered once daily at a dose as specified in the treatment arm; Other Names: BGB-11417
Experimental: Sonrotoclax Monotherapy Expansion Cohorts: Part 2; 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.	Drug: Sonrotoclax; Film-coated tablets administered once daily at a dose as specified in the treatment arm; Other Names: BGB-11417
Experimental: Sonrotoclax + Zanubrutinib Combination Therapy Dose Finding: Part 3; Participants with R/R MCL, R/R or treatment-naïve (TN) CLL/SLL will receive oral sonrotoclax in combination with zanubrutinib.	Drug: 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); Other Names: BGB-3111; Drug: Sonrotoclax; Film-coated tablets administered once daily at a dose as specified in the treatment arm; Other Names: BGB-11417
Experimental: Sonrotoclax + Zanubrutinib Combination Therapy Dose Expansion: Part 4; 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.	Drug: 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); Other Names: BGB-3111; Drug: Sonrotoclax; Film-coated tablets administered once daily at a dose as specified in the treatment arm; Other Names: BGB-11417
Experimental: Sonrotoclax + Zanubrutinib Combination Therapy Dose Escalation: Part 5; Participants with treatment naïve CLL/SLL will receive oral sonrotoclax in combination with obinutuzumab without and with zanubrutinib.	Drug: 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); Other Names: BGB-3111; Drug: Sonrotoclax; Film-coated tablets administered once daily at a dose as specified in the treatment arm; Other Names: BGB-11417; Drug: Obinutuzumab; Given as an intravenous infusion administered per label.
Experimental: Sonrotoclax + Zanubrutinib Combination Therapy Dose Expansion: Part 6; 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.	Drug: 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); Other Names: BGB-3111; Drug: Sonrotoclax; Film-coated tablets administered once daily at a dose as specified in the treatment arm; Other Names: BGB-11417; Drug: Obinutuzumab; Given as an intravenous infusion administered per label.

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Part 3, Part 4: Steady State Maximum Observed Plasma Concentration (Cmax, ss) of zanubrutinib		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
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
Steady State Maximum Observed Plasma Concentration (Cmax, ss) of Sonrotoclax		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 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	ORR is defined as the proportion of participants who had confirmed complete response Complete Response (CR) or Partial Response (PR)	Up to 18 months
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

Collaborators and Investigators

• Sponsor: BeOne Medicines
• Investigators: Study Director: Study Director, BeOne Medicines

Study record dates

Study Major Dates

• Study Start (Actual): March 24, 2020
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): May 31, 2027

Study Registration Dates

• First Submitted: February 18, 2020
• First Submitted That Met QC Criteria: February 18, 2020
• First Posted (Actual): February 20, 2020

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: NHL; MCL; MZL; CLL; SLL; BTKi; WM; BCL2 Inhibitor; Bcl-2i
• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents, Immunological; Tyrosine Kinase Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; zanubrutinib; obinutuzumab
• Other Study ID Numbers: BGB-11417-101; 2024-515592-35-00 (Ctis); 2020-004641-37 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

BeOne shares data on completed studies responsibly and provides qualified scientific and medical researchers access to data and supporting documentation for clinical trials in dossiers for medicines and indications after submission and approval in the United States, China, and Europe. Clinical trials supporting subsequent local approvals, new indications, or combination products are eligible for sharing once corresponding regulatory approvals are achieved.

BeOne shares data only when permitted by applicable data privacy and security laws and regulations, when it is feasible to do so without compromising the privacy of study participants, and other considerations.

Qualified researchers with appropriate competencies who are engaged in novel scientific research may submit a request for participant-level data with a research proposal for BeOne review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.

• IPD Sharing Time Frame: See plan description
• IPD Sharing Access Criteria: See plan description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No