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

BeiGene

Status and phase: Enrolling; 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

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 Expansion."

Enrollment: 85 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
   2. R/R FL
   3. R/R MZL
   4. Transformed B-cell NHL
   5. Richter's transformation to DLBCL

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
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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85 participants in 3 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): BGB-21447 Monotherapy Dose Expansion

Experimental group

Description:

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

Treatment:

Drug: BGB-21447