Recruiting
Phase 1/Phase 2
A Dose-Escalation and Expansion Study of Tacabrutideg (BGB-16673) in Participants With B-Cell Malignancies
Condition(s) studied
B-cell MalignancyMarginal Zone LymphomaFollicular LymphomaNon-Hodgkin LymphomaWaldenström MacroglobulinemiaChronic Lymphocytic LeukemiaSmall Lymphocytic LymphomaMantle Cell LymphomaDiffuse Large B Cell Lymphoma
Investigational drug(s) / intervention(s)
Tacabrutideg
Tacabrutideg: Orally administered
Study summary
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)
Eligibility
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. Phase 2 Cohorts in R/R CLL/SLL, R/R MCL, and R/R WM only: Participants who previously received a BTKi are eligible if they had disease progression on only one regimen containing a covalent BTKi. Note: Participants may have received treatment with ≥ 2 different covalent BTKis if additional BTKis were discontinued secondary to an event other than disease progression.
5. Measurable disease by radiographic assessment or serum IgM level (WM only)
6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2
7. 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.
Primary outcome measure(s)
- Phase 1: Number of Participants with Adverse Events (AEs) — From the first dose of tacabrutideg until 30 days after the last dose of the study drug or before the initiation of a new anticancer therapy, whichever occurs first (Up to 47 weeks)
Number of participants with Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) including results from laboratory assessments, electrocardiograms (ECGs), and physical examinations, and that meet protocol-defined dose-limiting toxicities (DLTs); as graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0.
- Phase 1: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of Tacabrutideg — Approximately 28 days
MTD is defined as the highest evaluated dose with an estimated toxicity rate closest to the target, while MAD is the highest dose given if MTD is not reached.
- Phase 1: Recommended dose(s) for Expansion (RDFE) of tacabrutideg — Approximately 3 years
RDFE of tacabrutideg alone will be determined based upon the MTD or MAD.
- Phase 2: Overall response rate (ORR) — approximately 3 years
Defined as the percentage of participants achieving a best overall response of partial response (PR) or better, assessed by the Independent Review Committee for participants with R/R CLL/SLL and R/R WM (in participants with WM, this is also referred to as major response rate) and by the investigator for other cohorts (R/R MCL, R/R MZL, R/R FL, R/R non-GCB DLBCL, R/R Richter's transformation to DLBCL), evaluated using the Lugano criteria for NHL and SLL, International Workshop of Chronic Lymphocytic Leukemia (iwCLL) criteria for CLL, and the 11th International Workshop on Waldenstrom's Macroglobulinemia (IWWM-11) criteria for WM.
Trial sites (115)
| Facility | City | Region | Status |
| University of Alabama At Birmingham Hospital |
Birmingham |
Alabama |
Recruiting |
| Mayo Clinic Phoenix |
Phoenix |
Arizona |
Completed |
| Honor Health Research Institute |
Scottsdale |
Arizona |
Recruiting |
| University of Arizona Cancer Center |
Tucson |
Arizona |
Recruiting |
| University of California San Diego (Ucsd) Moores Cancer Center |
La Jolla |
California |
Recruiting |
| Stanford Medicine |
Palo Alto |
California |
Recruiting |
| UCLA Santa Monica Cancer Care |
Santa Monica |
California |
Recruiting |
| Uchealth North |
Fort Collins |
Colorado |
Recruiting |
| Mayo Clinic Jacksonville |
Jacksonville |
Florida |
Recruiting |
| Mount Sinai Medical Center Braman Comprehensive Cancer Center |
Miami |
Florida |
Recruiting |
| Tampa General Hospital Cancer Institute |
Tampa |
Florida |
Recruiting |
| Augusta University |
Augusta |
Georgia |
Recruiting |
| Southeastern Regional Medical Center |
Newnan |
Georgia |
Recruiting |
| Midwestern Regional Medical Center |
Zion |
Illinois |
Completed |
| University of Iowa Hospitals and Clinics |
Iowa City |
Iowa |
Recruiting |
| Norton Cancer Institute Pavilion |
Louisville |
Kentucky |
Active Not Recruiting |
| Mary Bird Perkins Cancer Center |
Baton Rouge |
Louisiana |
Recruiting |
| American Oncology Partners of Maryland Pa |
Bethesda |
Maryland |
Recruiting |
| Dana Farber Cancer Institute |
Boston |
Massachusetts |
Recruiting |
| Karmanos Cancer Institute |
Detroit |
Michigan |
Recruiting |
| Mayo Clinic Rochester |
Rochester |
Minnesota |
Recruiting |
| Comprehensive Cancer Centers of Nevada |
Las Vegas |
Nevada |
Recruiting |
| Roswell Park Comprehensive Cancer Center |
Buffalo |
New York |
Recruiting |
| Columbia University Medical Center |
New York |
New York |
Recruiting |
| Weill Cornell Medical College Newyork Presbyterian Hospital |
New York |
New York |
Recruiting |
| Memorial Sloan Kettering Cancer Center Mskcc |
New York |
New York |
Recruiting |
| Tennesse Oncology Chattanooga Downtown |
Chattanooga |
Tennessee |
Recruiting |
| Tennessee Oncology, Pllc Nashville |
Nashville |
Tennessee |
Recruiting |
| Md Anderson Cancer Center |
Houston |
Texas |
Recruiting |
| Virginia Commonwealth University Massey Cancer Center |
Richmond |
Virginia |
Recruiting |
| Fred Hutchinson Cancer Research Center |
Seattle |
Washington |
Recruiting |
| Concord Repatriation General Hospital |
Concord |
New South Wales |
Recruiting |
| Calvary Mater Newcastle |
Waratah |
New South Wales |
Recruiting |
| Princess Alexandra Hospital |
Woolloongabba |
Queensland |
Recruiting |
| St Vincents Hospital Melbourne |
Fitzroy |
Victoria |
Recruiting |
| Austin Health |
Heidelberg |
Victoria |
Recruiting |
| Peter Maccallum Cancer Centre |
Melbourne |
Victoria |
Recruiting |
| The Alfred Hospital |
Melbourne |
Victoria |
Recruiting |
| Linear Clinical Research |
Nedlands |
Western Australia |
Recruiting |
| Perth Blood Institute |
West Perth |
Western Australia |
Recruiting |
+ 75 more sites — see the full list on the official registry below.