A Study of BGB-21447, a Bcl-2 Inhibitor, in Mature B-Cell Malignancies

BeOne Medicines

Status and phase: Active, not recruiting; Phase 1

Conditions: Refractory Small Lymphocytic Lymphoma; Transformed Non-Hodgkin Lymphoma; Refractory Diffuse Large B-cell Lymphoma; Relapsed Non-Hodgkin Lymphoma; Relapsed Chronic Lymphocytic Leukemia; Richter Transformation; Relapsed Follicular Lymphoma; Relapsed Marginal Zone Lymphoma; Refractory Marginal Zone Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Follicular Lymphoma; Relapsed Small Lymphocytic Lymphoma; Relapse Diffuse Large B Cell Lymphoma; Refractory Non-Hodgkin Lymphoma

Treatments: Drug: BGB-21447

Study type: Interventional

Funder types: Industry

Identifiers

NCT05828589

CTR20231287 (Registry Identifier)

BGB-21447-101

2025-521600-21-00 (EU Trial (CTIS) Number)

CT-2023-CTN-05421-1 (Other Identifier)

Details and patient eligibility

About

This study is testing the safety and tolerability of BGB-21447 monotherapy in participants with relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The study aims to determine the maximum tolerated dose (MTD), maximum administered dose (MAD), recommended Phase 2 dose (RP2D), and pharmacokinetic profile of the drug. Additionally, preliminary antitumor activity will be characterized. The study is divided into 2 main parts: Part 1 "Monotherapy Dose Finding" and Part 2 "Monotherapy Dose Optimization."

Full 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.

Enrollment: 112 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

1. Confirmed diagnosis (per World Health Organization [WHO] guidelines, unless otherwise noted) of one of the following:

   Cohort A1 and Cohort A2:

   1. R/R DLBCL (for Cohort A1 and Cohort A2.1)

      • High-grade B-cell lymphomas with translocations of MYC and Bcl-2 and/or Bcl-6 are not allowed in Cohort A1 but may be allowed in Cohort A2.1

   2. R/R FL (for Cohort A1 and Cohort A2.2)

   3. R/R MZL (for Cohort A1 and Cohort A2.2)

   4. Transformed B-cell NHL (for Cohort A1 only)

   5. Richter's transformation to DLBCL (for Cohort A1 only)

2. Measurable disease by computed tomography/magnetic resonance imaging.

Exclusion Criteria:

1. Prior malignancy (other than the disease under study) within the past 2 years, except for curatively treated basal or squamous skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score ≤ 6 prostate cancer or lentigo maligna melanoma that has been curatively resected
2. Known central nervous system involvement by lymphoma/leukemia
3. Prior autologous stem cell transplant < 3 months before the first dose of study drug. Or prior chimeric antigen receptor T-cell (CAR-T) therapy < 3 months before the first dose of study drug
4. Prior allogeneic stem cell transplant.
5. Major surgery < 4 weeks before the first dose of study treatment

NOTE: Other protocol-defined Inclusion/Exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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112 participants in 4 patient groups

Part 1 (Cohort A1): Dose escalation in patients with B-cell non-Hodgkin lymphoma (NHL)

Experimental group

Description:

Participants with R/R B-cell NHL (including diffuse large B-cell lymphoma \[DLBCL\], follicular lymphoma \[FL\], marginal zone lymphoma \[MZL\], transformed B-cell NHL (B-NHL), and Richter's transformation to DLBCL) will receive BGB-21447 once a day.

Treatment:

Drug: BGB-21447

Part 1 (Cohort B): Dose escalation in R/R CLL/SLL participants with low tumor burden

Experimental group

Description:

Participants with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) will receive BGB-21447 once a day.

Treatment:

Drug: BGB-21447

Part 2 (Cohort A2.1): BGB-21447 Monotherapy Dose Optimization in R/R DLBCL

Experimental group

Description:

Participants will receive BGB-21447 with two dose levels from Cohort A1 for further evaluation of safety and efficacy.

Treatment:

Drug: BGB-21447

Part 2 (Cohort A2.2): BGB-21447 Monotherapy Dose Optimization in R/R FL or R/R MZL

Experimental group

Description:

Participants will receive BGB-21447 with two dose levels from Cohort A1 for further evaluation of safety and efficacy.

Treatment:

Drug: BGB-21447