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

NCT ID: NCT04277637

Last Updated: 2025-02-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1

Total Enrollment

437 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-03-24

Study Completion Date

2027-08-30

Brief Summary

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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

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Conditions

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Mature B-Cell Malignancies

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Sonrotoclax

Intervention Type DRUG

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

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.

Group Type EXPERIMENTAL

Sonrotoclax

Intervention Type DRUG

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

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.

Group Type EXPERIMENTAL

Sonrotoclax

Intervention Type DRUG

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

Zanubrutinib

Intervention Type 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)

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.

Group Type EXPERIMENTAL

Sonrotoclax

Intervention Type DRUG

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

Zanubrutinib

Intervention Type 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)

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.

Group Type EXPERIMENTAL

Sonrotoclax

Intervention Type DRUG

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

Zanubrutinib

Intervention Type 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)

Obinutuzumab

Intervention Type DRUG

Given as an intravenous infusion administered per label.

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.

Group Type EXPERIMENTAL

Sonrotoclax

Intervention Type DRUG

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

Zanubrutinib

Intervention Type 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)

Obinutuzumab

Intervention Type DRUG

Given as an intravenous infusion administered per label.

Interventions

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Sonrotoclax

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

Intervention Type 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)

Intervention Type DRUG

Obinutuzumab

Given as an intravenous infusion administered per label.

Intervention Type DRUG

Other Intervention Names

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BGB-11417 BGB-3111

Eligibility Criteria

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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

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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BeiGene

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Study Director

Role: STUDY_DIRECTOR

BeiGene

Locations

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UCLA Hematologyoncology

Los Angeles, California, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

University of Kansas Medical Center Research Institute

Kansas City, Kansas, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Mayo Clinic Rochester

Rochester, Minnesota, United States

Site Status

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

John Theurer Cancer Center Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center Mskcc

New York, New York, United States

Site Status

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

Columbus, Ohio, United States

Site Status

Upmc Hillman Cancer Center(Univ of Pittsburgh)

Pittsburgh, Pennsylvania, United States

Site Status

Md Anderson Cancer Center

Houston, Texas, United States

Site Status

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Site Status

Concord Repatriation General Hospital

Concord, New South Wales, Australia

Site Status

Orange Health Service (Central West Cancer Care Centre)

Orange, New South Wales, Australia

Site Status

Pindara Private Hospital

Benowa, Queensland, Australia

Site Status

John Flynn Private Hospital

Tugun, Queensland, Australia

Site Status

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Site Status

Flinders Medical Centre

Bedford PK, South Australia, Australia

Site Status

Box Hill Hospital

Box Hill, Victoria, Australia

Site Status

Monash Health

Clayton, Victoria, Australia

Site Status

St Vincents Hospital Melbourne

Fitzroy, Victoria, Australia

Site Status

Peter Maccallum Cancer Centre

Melbourne, Victoria, Australia

Site Status

The Alfred Hospital

Melbourne, Victoria, Australia

Site Status

Linear Clinical Research

Nedlands, Western Australia, Australia

Site Status

Universitatsklinikum Carl Gustav Carus An Der Technischen Universitat Dresden

Dresden, , Germany

Site Status

Ospedale San Raffaele

Milan, , Italy

Site Status

Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda

Milan, , Italy

Site Status

Ospedale Santa Maria Della Misericordia

Perugia, , Italy

Site Status

Azienda Unita Sanitaria Locale Di Ravenna

Ravenna, , Italy

Site Status

Fondazione Policlinico Universitario Agostino Gemelli

Roma, , Italy

Site Status

Centroricerche Cliniche Di Verona Srl

Verona, , Italy

Site Status

Auckland City Hospital

Auckland, , New Zealand

Site Status

North Shore Hospital

Takapuna, , New Zealand

Site Status

Wellington Regional Hospital (Ccdhb)

Wellington, , New Zealand

Site Status

Hospital de La Santa Creu I Sant Pau

Barcelona, , Spain

Site Status

Vall D Hebron Institute of Oncology Vhio

Barcelona, , Spain

Site Status

Ico H Duran I Reynals

Barcelona, , Spain

Site Status

Hospital Clinic de Barcelona

Barcelona, , Spain

Site Status

Start Madrid Fundacion Jimenez Diaz

Madrid, , Spain

Site Status

Clinica Universidad de Navarra Pamplona

Pamplona, , Spain

Site Status

Hospital Universitario de Salamanca

Salamanca, , Spain

Site Status

Hospital Universitario Marques de Valdecilla

Santander, , Spain

Site Status

The Leeds Teaching Hospitals Nhs Trust

Leeds, , United Kingdom

Site Status

Countries

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United States Australia Germany Italy New Zealand Spain United Kingdom

Other Identifiers

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2024-515592-35-00

Identifier Type: CTIS

Identifier Source: secondary_id

2020-004641-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BGB-11417-101

Identifier Type: -

Identifier Source: org_study_id

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