Phase 1 Study of BGB-21447, a Bcl-2 Inhibitor, in Mature B-Cell Malignancies
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohort A: Dose escalation in participants with non-Hodgkin lymphoma Participants will receive BGB-21447 once a day, starting with a small dose and increasing to higher doses one at a time. |
Drug: BGB-21447
BGB-21447 will be administered orally
|
| Experimental: Cohort B: Dose escalation in R/R CLL/SLL participants with low tumor burden Participants will receive BGB-21447 once a day, starting with a small doses and increasing to higher doses one at a time. |
Drug: BGB-21447
BGB-21447 will be administered orally
|
| Experimental: Cohort C: Dose confirmation in R/R CLL/SLL participants with high tumor burden Participants will receive BGB-21447 dose as determine in determined in cohort B. |
Drug: BGB-21447
BGB-21447 will be administered orally
|
Outcome Measures
Primary Outcome Measures
- Number of participants with dose limiting toxicities (DLTs) [Up to 4 Years]
Number of participants with dose limiting toxicities, defined as [see text in SAP or protocol for specific definition]
- Number of participants with adverse events (AEs) [Up to 4 Years]
Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) assessed and graded based upon the National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v5.0).
- Number of participants with Tumor Lysis Syndrome (TLS) [Up to 4 Years]
TLS will be determined via laboratory values and assessed by the investigator. In laboratory tumor lysis syndrome, 2 or more metabolic abnormalities must be present during the 24-hour period within 3 days before the start of study drug treatment or up to 7 days afterward. Clinical tumor lysis syndrome requires the presence of laboratory tumor lysis syndrome plus an increased creatinine level, seizures, cardiac dysrhythmia, or death.
Secondary Outcome Measures
- Maximum observed plasma concentration (Cmax) of BGB-21447 [Up to 4 Years]
- Pre-dose trough concentration (Ctrough) of BGB-21447 [Up to 4 Years]
- Area under the curve from time 0 to the last sampling time point within the dose interval (AUClast) of BGB-21447 [Up to 4 Years]
- Area under the curve from time 0 extrapolated to infinity (AUCinf) of BGB-21447 [Up to 4 Years]
- Time to reach maximum observed plasma concentration (Tmax) of BGB-21447 [Up to 4 Years]
- Apparent terminal elimination half life (t1/2) of BGB-21447 [Up to 4 Years]
- Apparent oral clearance (CL/F) of BGB-21447 [Up to 4 Years]
- Apparent volume of distribution (Vz/F) of BGB-21447 [Up to 4 Years]
- Steady state maximum observed plasma concentration (Cmax) of BGB-21447 [Up to 4 Years]
- Steady state pre-dose trough concentration (Ctrough) of BGB-21447 [Up to 4 Years]
- Steady state area under the curve from time 0 to the last sampling time point within the dose interval (AUClast) of *drug name* [Up to 4 Years]
- Steady state area under the curve from time 0 extrapolated to infinity (AUCinf) of BGB-21447 [Up to 4 Years]
- Steady state time to reach maximum observed plasma concentration (Tmax) of BGB-21447 [Up to 4 Years]
- Steady state apparent terminal elimination half life (t1/2) of BGB-21447 [Up to 4 Years]
- Steady state apparent oral clearance (CL/F) of BGB-21447 [Up to 4 Years]
- Steady state apparent volume of distribution (Vz/F) of BGB-21447 [Up to 4 Years]
Eligibility Criteria
Criteria
Inclusion Criteria
- Confirmed diagnosis per WHO guidelines of one of the following:
Cohort A:
-
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)
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R/R Follicular lymphoma (FL):
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R/R Marginal zone lymphoma (MZL)
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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
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Measurable disease by computed tomography (CT)/magnetic resonance imaging (MRI),
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CLL: at least 1 lymph node > 1.5 cm in longest diameter and measurable in 2 perpendicular dimensions or clonal lymphocytes on flow cytometry
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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:
-
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
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Known central nervous system involvement by lymphoma/leukemia
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Known history or currently suspected Richter's syndrome
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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
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Prior allogeneic stem cell transplant.
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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:
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Any biologic and/or immunologic-based therapy(ies) ≤ 28 days before the first dose of study drug
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Any systemic chemotherapy or radiation therapy ≤ 14 days before the first dose of study drug
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Any targeted small molecule agents ≤ 14 days before the first dose of study drug
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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.
-
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.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- BeiGene
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BGB-21447-101