A Dose-Escalation and Expansion Study of BGB-16673 in Participants With B-Cell Malignancies

BeiGene

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Waldenström Macroglobulinemia; Marginal Zone Lymphoma; Mantle Cell Lymphoma; Small Lymphocytic Lymphoma; Follicular Lymphoma; Chronic Lymphocytic Leukemia; B-cell Malignancy; Diffuse Large B Cell Lymphoma; Non-Hodgkin Lymphoma

Treatments: Drug: BGB-16673

Study type: Interventional

Funder types: Industry

Identifiers

NCT05006716

BGB-16673-101

2022-502157-33-00 (Other Identifier)

Details and patient eligibility

About

Study consists of two main parts to explore BGB-16673 recommended dosing, a Phase 1 monotherapy dose finding comprised of monotherapy dose escalation and monotherapy safety expansion of selected doses, and a Phase 2 (expansion cohorts)

Enrollment: 466 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: Marginal Zone Lymphoma (MZL) , Follicular Lymphoma (FL), R/R Mantle Cell Lymphoma (MCL), R/R chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL), Waldenström macroglobulinemia (WM), Diffuse large B-cell lymphoma (DLBCL), or >2 treatments per the Richter's transformation to DLBCL.
2. Participants who have previously received a covalently-binding Bruton´s tyrosine kinase (BTK) inhibitor (BTKi) in any line of therapy must have received treatment with the BTK inhibitor for ≥ 8 weeks (unless reason for discontinuation is intolerance).
3. For dose-finding and dose-expansion, participants who had previously received a covalently-binding BTK inhibitor as monotherapy or in combination with other anticancer agents are eligible for the study if they meet any of the following criteria: discontinued the previous BTK inhibitor due to disease progression, experienced disease progression after completing treatment with a BTK inhibitor or discontinued the BTK inhibitor due to toxicity or intolerance.
4. Measurable disease by radiographic assessment or serum IgM level (WM only)
5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2
6. Participants enrolling in the dose finding phase of the study may be previously treated with a BTKi or may be naïve to BTKi therapy depending on the diagnosis and country of enrollment; participants with MCL enrolling in the expansion cohorts (Phase 2) must have been treated with a BTKi in a prior line of therapy; CLL/SLL participants, in addition to being treated with a BTKi in a prior line of therapy, must also have received a Bcl-2 inhibitor in a prior line of therapy as well (Phase 2).

Exclusion Criteria:

1. Prior malignancy (other than the disease under study) within the past 2 years, except in situ malignancies that have been curatively resected, localized breast cancer treated with curative intent with no evidence of breast active disease for more than 3 years and receiving adjuvant hormonal therapy, localized Gleason score ≤ 6 prostate cancer undergoing observation or treatment with androgen depravation, or any other cancer treated with curative intent, not on adjuvant treatment, and in the opinion of the investigator is unlikely to recur.
2. Requires ongoing systemic treatment for any other malignancy
3. Requires ongoing systemic (defined as ≥ 10 mg/day of prednisone or equivalent) corticosteroid treatment.
4. Current or history of central nervous system involvement including the brain, spinal cord, leptomeninges, and cerebrospinal fluid (as documented by imaging, cytology, or biopsy) by B-cell malignancy, regardless of whether participants had received treatment for central nervous system disease
5. Known active plasma cell neoplasm, prolymphocytic leukemia, T-cell lymphoma, Burkitt lymphoma, acquired immunodeficiency syndrome (AIDS)-related B-cell lymphoma, Castleman disease, post-transplant lymphoproliferative disorders, hairy cell leukemia, germinal center B-cell (GCB), DLBCL, EBV+ DLBCL NOS, primary DLBCL of the central nervous system (CNS), primary cutaneous DLBCL - leg type, DLBCL associated with chronic inflammation, primary mediastinal (thymic) large B-cell lymphoma, intravascular large B-cell lymphoma, ALK+ large B-cell lymphoma, primary effusion lymphoma, high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, high-grade B-cell lymphoma - NOS, B-cell lymphoma unclassifiable with features intermediate between DLBCL and classical Hodgkin lymphoma, or history of or currently suspected transformation of an indolent lymphoma to an aggressive histology (except for participants with Richter Transformation to DLBCL are eligible for Part 1a, 1c, or Phase 2 and participants with history of follicular lymphoma transforming to non-GCB DLBCL who are eligible for Part 1a, 1c, or Phase 2).

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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466 participants in 4 patient groups

Part 1a (Monotherapy Dose Escalation)

Experimental group

Description:

Dose escalation in selected R/R B-Cell malignancies to inform safety, tolerability and MTD.

Treatment:

Drug: BGB-16673

Part 1b (Monotherapy Safety Expansion)

Experimental group

Description:

Additional participants with selected R/R B-Cell malignancies will be enrolled at selected doses to help inform the selection of the recommended phase two dose (RP2D).

Treatment:

Drug: BGB-16673

Part 1c (Additional Monotherapy Safety Expansion)

Experimental group

Description:

After RP2D is determined, additional safety data will be collected to confirm RP2D for participants with selected B-cell malignancies not being evaluated in Part 2

Treatment:

Drug: BGB-16673

Part 2 (Monotherapy Expansion)

Experimental group

Description:

The totality of the data from Part 1a, Part 1b, and Part 1c will be used to further evaluate the safety and efficacy of BGB-16673 at the recommended dose(s) for Phase 2 expansion in specific histologies.

Treatment:

Drug: BGB-16673