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

NCT04277637 | Active Not Recruiting Phase 1 FDA Drug

• 3 other identifiers: BGB-11417-1012024-515592-35-002020-004641-37
• Study Type: interventional
• Target: 437
• Locations: 7 countries
• Sites: 43

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.

Conditions

Mature B-Cell Malignancies

Keywords

NHL; BCL2 Inhibitor; CLL; MCL; MZL; SLL; WM; Bcl-2i; BTKi

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (20)

• 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

Study Arms (6)

Sonrotoclax Monotherapy Dose Finding: Part 1

EXPERIMENTAL

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

Sonrotoclax Monotherapy Expansion Cohorts: Part 2

EXPERIMENTAL

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

Sonrotoclax + Zanubrutinib Combination Therapy Dose Finding: Part 3

EXPERIMENTAL

Participants with R/R MCL, R/R or treatment-naïve (TN) CLL/SLL will receive oral sonrotoclax in combination with zanubrutinib.

Drug: Sonrotoclax; Drug: Zanubrutinib

Sonrotoclax + Zanubrutinib Combination Therapy Dose Expansion: Part 4

EXPERIMENTAL

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: Sonrotoclax; Drug: Zanubrutinib

Sonrotoclax + Zanubrutinib Combination Therapy Dose Escalation: Part 5

EXPERIMENTAL

Participants with treatment naïve CLL/SLL will receive oral sonrotoclax in combination with obinutuzumab without and with zanubrutinib.

Drug: Sonrotoclax; Drug: Zanubrutinib; Drug: Obinutuzumab

Sonrotoclax + Zanubrutinib Combination Therapy Dose Expansion: Part 6

EXPERIMENTAL

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: Sonrotoclax; Drug: Zanubrutinib; Drug: Obinutuzumab

Interventions

Sonrotoclax DRUG

Film-coated tablets administered once daily at a dose as specified in the treatment arm

Also known as: BGB-11417

Sonrotoclax + Zanubrutinib Combination Therapy Dose Escalation: Part 5; Sonrotoclax + Zanubrutinib Combination Therapy Dose Expansion: Part 4; Sonrotoclax + Zanubrutinib Combination Therapy Dose Expansion: Part 6; Sonrotoclax + Zanubrutinib Combination Therapy Dose Finding: Part 3; Sonrotoclax Monotherapy Dose Finding: Part 1; Sonrotoclax Monotherapy Expansion Cohorts: Part 2

Zanubrutinib DRUG

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)

Also known as: BGB-3111

Sonrotoclax + Zanubrutinib Combination Therapy Dose Escalation: Part 5; Sonrotoclax + Zanubrutinib Combination Therapy Dose Expansion: Part 4; Sonrotoclax + Zanubrutinib Combination Therapy Dose Expansion: Part 6; Sonrotoclax + Zanubrutinib Combination Therapy Dose Finding: Part 3

Obinutuzumab DRUG

Given as an intravenous infusion administered per label.

Sonrotoclax + Zanubrutinib Combination Therapy Dose Escalation: Part 5; Sonrotoclax + Zanubrutinib Combination Therapy Dose Expansion: Part 6

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• BeOne Medicines: lead

Study Sites (43)

UCLA Hematologyoncology

Los Angeles, California, 90095-3075, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Kansas Medical Center Research Institute

Kansas City, Kansas, 66160-8500, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905-0001, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

John Theurer Cancer Center Hackensack University Medical Center

Hackensack, New Jersey, 07601-2191, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center Mskcc

New York, New York, 10065-6800, United States

Location

The James Cancer Hospital and Solove Research Institute At Ohio State University

Columbus, Ohio, 43210-1240, United States

Location

Upmc Hillman Cancer Center(Univ of Pittsburgh)

Pittsburgh, Pennsylvania, 15232-1309, United States

Location

Md Anderson Cancer Center

Houston, Texas, 77030-3907, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109-4433, United States

Location

Concord Repatriation General Hospital

Concord, New South Wales, NSW 2139, Australia

Location

Orange Health Service (Central West Cancer Care Centre)

Orange, New South Wales, NSW 2800, Australia

Location

Pindara Private Hospital

Benowa, Queensland, QLD 4217, Australia

Location

John Flynn Private Hospital

Tugun, Queensland, QLD 4224, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, SA 5000, Australia

Location

Flinders Medical Centre

Bedford PK, South Australia, SA 5042, Australia

Location

Box Hill Hospital

Box Hill, Victoria, VIC 3128, Australia

Location

Monash Health

Clayton, Victoria, VIC 3168, Australia

Location

St Vincents Hospital Melbourne

Fitzroy, Victoria, VIC 3065, Australia

Location

Peter Maccallum Cancer Centre

Melbourne, Victoria, VIC 3000, Australia

Location

The Alfred Hospital

Melbourne, Victoria, VIC 3004, Australia

Location

Linear Clinical Research

Nedlands, Western Australia, WA 6009, Australia

Location

Universitatsklinikum Carl Gustav Carus An Der Technischen Universitat Dresden

Dresden, 01307, Germany

Location

Ospedale San Raffaele

Milan, 20132, Italy

Location

Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy

Location

Ospedale Santa Maria Della Misericordia

Perugia, 6129, Italy

Location

Azienda Unita Sanitaria Locale Di Ravenna

Ravenna, 48121, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli

Roma, 00168, Italy

Location

Centroricerche Cliniche Di Verona Srl

Verona, 37134, Italy

Location

North Shore Hospital

Auckland, 0622, New Zealand

Location

Auckland City Hospital

Auckland, 1023, New Zealand

Location

Wellington Regional Hospital (Ccdhb)

Wellington, 6021, New Zealand

Location

Vall D Hebron Institute of Oncology Vhio

Barcelona, 08035, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hospital de La Santa Creu I Sant Pau

Barcelona, 08041, Spain

Location

Ico H Duran I Reynals

Barcelona, 08907, Spain

Location

Start Madrid Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitario Marques de Valdecilla

Santander, 39008, Spain

Location

The Leeds Teaching Hospitals Nhs Trust

Leeds, LS9 7TF, United Kingdom

Location

MeSH Terms

Interventions

zanubrutinib; obinutuzumab

Study Officials

• Study Director

  BeOne Medicines

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 18, 2020
• First Posted: February 20, 2020
• Study Start: March 24, 2020
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): May 31, 2027
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: See plan description
• Access Criteria: See plan description

Locations

US (13); ES (7); DE (1); NZ (3); AU (12); GB (1); IT (6)