A Dose-Escalation and Expansion Study of Tacabrutideg (BGB-16673) in Participants With B-Cell Malignancies (CaDAnCe-101)

BeOne Medicines

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Richter Transformation; 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: Tacabrutideg

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 tacabrutideg 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)

Full description

A B-cell malignancy is a type of cancer that starts in white blood cells called B-cells. These cancers can affect the lymph nodes, bone marrow, blood, spleen, and other organs. Examples of these cancers include chronic lymphocytic leukemia/small lymphocytic lymphoma, marginal zone lymphoma, follicular lymphoma, Waldenström macroglobulinemia, mantle cell lymphoma, and diffuse large B cell lymphoma.

Tacabrutideg is a type of medicine called a BTK degrader. BTK (Bruton's tyrosine kinase) is a protein that helps cancer cells survive. Tacabrutideg is designed to attach to the BTK protein and tag it for removal, so that the body's own cellular "clean-up" system breaks it down and clears it away. When more BTK is removed from the body, it interferes with the signals needed for the cancer cells to multiply and survive and may also reduce the chance of the cancer becoming resistant to treatment.

The purpose of this study is to test whether tacabrutideg is safe and if it can treat B-cell malignancies. The main goals are to ensure the drug is safe by monitoring side effects and to understand how well patients respond to the treatment and whether their cancers shrink or disappear.

This study consists of two parts: dose escalation and dose expansion. During the dose escalation part, the study doctors will test different doses of the study drug to find the recommended dose that people can take without having serious side effects. During the dose expansion part, the study doctors will test the study drug in a larger number of people using the dose or doses identified from dose escalation. The study is open label, which means that the participants and the study doctors will know what treatment is received.

This study will enroll approximately 689 participants with B-cell malignancies at multiple centers worldwide.

The overall time to participate in this study is approximately 3 years. Participants will make regular visits to the clinic for treatment, health checks, blood tests, and tumor and imaging tests.

Our company, previously known as BeiGene, is now officially BeOne Medicines. Because some of our older studies were sponsored under the name BeiGene, you may see both names used for this study on this website.

Enrollment: 689 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), R/R follicular lymphoma (FL), mantle cell lymphoma (MCL), chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL), Waldenström macroglobulinemia (WM), R/R diffuse large B-cell lymphoma (DLBCL), or 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: Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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689 participants in 7 patient groups

Part 1a (Monotherapy Dose Escalation)

Experimental group

Description:

Dose escalation in specific subtypes of non-Hodgkin lymphoma (NHL), including relapsed or refractory (R/R) marginal zone lymphoma (MZL), R/R follicular lymphoma (FL) Grades 1, 2, and 3a, R/R mantle cell lymphoma (MCL), R/R chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), R/R diffuse large B-cell lymphoma (DLBCL), R/R Richter's transformation (RT), and R/R Waldenström macroglobulinemia (WM), to evaluate the safety and tolerability of tacabrutideg.

Treatment:

Drug: Tacabrutideg

Part 1b (Monotherapy Safety Expansion)

Experimental group

Description:

Participants with R/R MZL, MCL, CLL/SLL, and WM will be enrolled at selected doses to help determine the recommended dose(s) for expansion (RDFE(s)) for tacabrutideg.

Treatment:

Drug: Tacabrutideg

Part 1c (Additional Monotherapy Safety Expansion)

Experimental group

Description:

Additional safety data will be collected from participants with R/R MZL, WM, RT, DLBCL, or FL to confirm the RDFE(s) of tacabrutideg for those with non-CLL/SLL/MCL histologies.

Treatment:

Drug: Tacabrutideg

Part 1d (Additional Monotherapy Safety Expansion in R/R CLL/SLL)

Experimental group

Description:

Participants with R/R CLL/SLL will be enrolled at selected RDFE(s) to generate additional safety and efficacy data for tacabrutideg.

Treatment:

Drug: Tacabrutideg

Part 1e (Japan-only Cohort)

Experimental group

Description:

Japanese participants with R/R MZL, FL, MCL, CLL/SLL, and WM will be enrolled at selected RDFE(s) to assess the safety and tolerability of tacabrutideg.

Treatment:

Drug: Tacabrutideg

Part 1f (Additional Monotherapy Safety Expansion in BTKi Naive B-Cell Malignancies)

Experimental group

Description:

Participants with CLL/SLL, MCL, WM, MZL, or Richter's transformation to DLBCL who have not received a prior BTKi (either covalent or noncovalent) will be enrolled at selected dose levels.

Treatment:

Drug: Tacabrutideg

Phase 2 (Monotherapy Expansion)

Experimental group

Description:

Cohorts of participants with R/R CLL/SLL, R/R MCL, R/R WM, R/R MZL, R/R FL, R/R RT, and R/R DLBCL will be enrolled to receive the RDFE(s) identified in Phase 1 to further evaluate the safety and efficacy of tacabrutideg.

Treatment:

Drug: Tacabrutideg