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

Phase 1Active Not RecruitingNCT05828589

BeiGene112 enrolled

Overview

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."

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

112

Conditions

Relapsed Non-Hodgkin Lymphoma Refractory Non-Hodgkin Lymphoma Relapsed Chronic Lymphocytic Leukemia Refractory Chronic Lymphocytic Leukemia

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Part 1: Number of participants with dose limiting toxicities (DLTs)

Number of participants with dose limiting toxicities, as defined in the study protocol.

Time frame: Up to approximately 1 month

Number of participants with adverse events (AEs)

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).

Time frame: From the first dose of study drug to 30 days after the last dose or initiation of new anticancer therapy, whichever occurs first; up to approximately 12 months

Number of participants with Tumor Lysis Syndrome (TLS)

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.

Time frame: From the first dose of study drug to 30 days after the last dose or initiation of new anticancer therapy, whichever occurs first; up to approximately 12 months