Phase 1 Study of BGB-21447, a Bcl-2 Inhibitor, in Mature B-Cell Malignancies

• Status: Not yet recruiting
• Trial end date: 2026-10-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a Phase 1 study 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, recommended Phase 2 dose, and pharmacokinetic profile of the drug. Additionally, preliminary antitumor activity will be characterized. The study includes three cohorts and will also evaluate the safety and tolerability of a ramp-up dosing schedule.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: BeiGene

Criteria

Inclusion Criteria

1. Confirmed diagnosis per WHO guidelines of one of the following:

Cohort A:

1. Relapsed/refractory (R/R) Diffuse large B-cell lymphoma (DLBCL)(excluding high-grade B-cell lymphomas with translocations of MYC and Bcl-2 and/or Bcl-2; primary cutaneous DLBCL, leg type; gray zone lymphoma; and primary mediastinal large B-cell lymphoma)

2. R/R Follicular lymphoma (FL):

3. R/R Marginal zone lymphoma (MZL)

4. Transformed B-Cell non-Hodgkin lymphoma (NHL)

Cohorts B and C:

R/R CLL/SLL diagnosis that meets the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria

2. Measurable disease by computed tomography (CT)/magnetic resonance imaging (MRI),

1. CLL: at least 1 lymph node > 1.5 cm in longest diameter and measurable in 2 perpendicular dimensions or clonal lymphocytes on flow cytometry

2. DLBCL, FL, MZL, 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 2 perpendicular dimensions. For MZL, isolated splenomegaly is considered measurable.

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. Known history or currently suspected Richter's syndrome

4. 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

5. Prior allogeneic stem cell transplant.

6. Major surgery < 4 weeks before the first dose of study treatment

Use of the following substances prior to the first dose of the study drug:

1. Any biologic and/or immunologic-based therapy(ies) ≤ 28 days before the first dose of study drug

2. Any systemic chemotherapy or radiation therapy ≤ 14 days before the first dose of study drug

3. Any targeted small molecule agents ≤ 14 days before the first dose of study drug

4. Corticosteroid given with antineoplastic intent ≤ 7 days before the first dose of study drug. Short course of systemic corticosteroid treatment for control of lymphomarelated symptoms is allowed prior to enrollment, provided it is tapered off within 5 days after initiation of study treatment.

5. Any treatment with a strong/moderate cytochrome P450 (CYP)3A inhibitor or inducer ≤ 14 days (or 5 half-lives for inhibitors, whichever is longer) before the first dose of study drug OR requiring long-term use of strong CYP3A inhibitors or inducers

NOTE: Other Inclusion/Exclusion criteria may apply.