Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as BGB-16673, [14C]-BGB-16673
Tacabrutideg · 7 trials · 18 indications
PFS is defined as time from the date of randomization to the date of first disease progression or death, whichever occurs first, as determined by IRC using modified 2018 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria for participants with chronic lymphocytic leukemia (CLL) and Lugano classification for participants with small lymphocytic lymphoma (SLL).
PFS is defined as time from the date of randomization to the date of first disease progression or death, whichever occurs first, as determined by IRC using modified 2018 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria for participants with R/R CLL and the Lugano Classification for patients with R/R SLL.
PFS is defined as time from the date of randomization to the date of first disease progression or death, whichever occurs first, as determined by IRC using modified 2018 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria for participants with chronic lymphocytic leukemia (CLL) and Lugano classification for participants with small lymphocytic lymphoma (SLL).
Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including findings from laboratory tests and electrocardiogram results.
Number of participants with TEAEs and SAEs, including findings from laboratory tests and electrocardiogram results.
Number of participants with AEs and SAEs as graded by the National Cancer Institute- Common Terminology Criteria for Adverse Events Version 5 (NCI CTCAE 5.0), including AEs that meet protocol-defined dose-limiting toxicity (DLT) criteria.
As determined by the sponsor based on the Safety Monitoring Committee's recommendation considering totality of the available clinical safety, clinical efficacy, pharmacokinetics, and pharmacodynamics data.
The highest dose evaluated as recommended by the Bayesian Optimal Interval Design with Informative Prior (iBOIN) design or the maximum assessed dose (MAD).
ORR is defined as the percentage of participants with partial response or better according to the Independent Review Committee (IRC) assessment and as determined by Lugano criteria.
ORR is defined as the percentage of participants with partial response or better as assessed by the IRC and determined by the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria for CLL and by Lugano criteria for SLL
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.
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.
RDFE of tacabrutideg alone will be determined based upon the MTD or MAD.
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.
| Arm | Type | Description |
|---|---|---|
| Arm A: Tacabrutideg | EXPERIMENTAL | Participants will receive tacabrutideg orally. |
| Arm B: Pirtobrutinib | ACTIVE_COMPARATOR | Participants will receive pirtobrutinib orally. |
| Arm A: BGB-16673 Monotherapy | EXPERIMENTAL | Participants will receive BGB-16673 once daily until any of the treatment discontinuation criteria are met |
| Arm B: Investigator's Choice | ACTIVE_COMPARATOR | Participants will receive investigator's choice of bendamustine plus rituximab or high-dose methylprednisolone plus rituximab or chlorambucil plus obinutuzumab for up to six 28-day cycles. Participants with unequivocal disease progression confirmed by Independent Review Committee (IRC) may cross over to receive treatment with BGB-16673 at the Investigator's discretion |
| Arm A: Tacabrutideg monotherapy | EXPERIMENTAL | Participants will receive tacabrutideg once daily until any of the treatment discontinuation criteria are met |
| Part A (CSU): Tacabrutideg | EXPERIMENTAL | Sequential cohorts of increasing dose levels of tacabrutideg will be evaluated in participants with CSU. |
| Part A (CSU): Placebo | PLACEBO_COMPARATOR | Participants with CSU will receive matching placebo orally for 28 days and then crossover to receive tacabrutideg. |
| Part B (Healthy Participants): Tacabrutideg | EXPERIMENTAL | Sequential cohorts of increasing dose levels of tacabrutideg will be evaluated in healthy participants. |
| Substudy 1 Part 1a: Dose Escalation | EXPERIMENTAL | Sequential cohorts of increasing dose level combinations of tacabrutideg and sonrotoclax will be evaluated in participants with selected B-cell malignancies. |
| Substudy 1 Part 1b: Safety Expansion | EXPERIMENTAL | Cohorts of select dose level combinations of tacabrutideg and sonrotoclax will be evaluated in participants with selected B-cell malignancies. |
| Substudy 2 Part 1a: Dose Escalation | EXPERIMENTAL | Sequential cohorts of increasing dose level combinations of tacabrutideg and zanubrutinib will be evaluated in participants with selected B-cell malignancies. |
| Substudy 2 Part 1b: Safety Expansion | EXPERIMENTAL | Cohorts of select dose level combinations of tacabrutideg and zanubrutinib will be evaluated in participants with selected B-cell malignancies. |
| Substudy 3 Part 1a: Dose Escalation | EXPERIMENTAL | Sequential cohorts of increasing dose level combinations of tacabrutideg and mosunetuzumab will be evaluated in participants with selected B-cell malignancies. |
| Substudy 3 Part 1b: Safety Expansion | EXPERIMENTAL | Cohorts of select dose level combinations of tacabrutideg and mosunetuzumab will be evaluated in participants with selected B-cell malignancies. |
| Substudy 4 Part 1a: Dose Escalation | EXPERIMENTAL | Sequential cohorts of increasing dose level combinations of tacabrutideg and glofitamab will be evaluated in participants with selected B-cell malignancies. Participants will receive obinutuzumab as pretreatment prior to the start of combination treatment. |
| Substudy 4 Part 1b: Safety Expansion | EXPERIMENTAL | Cohorts of select dose level combinations of tacabrutideg and glofitamab will be evaluated in participants with selected B-cell malignancies. |
| Phase 1a Monotherapy Dose Escalation | EXPERIMENTAL | BGB-16673 will be orally administered. |
| Phase 1b Monotherapy Safety Expansion | EXPERIMENTAL | BGB-16673 will be orally administered. |
| Phase 2 Monotherapy Dose Expansion | EXPERIMENTAL | BGB-16673 will be administered at the recommended Phase 2 dose (RP2D) that was identified in Part 1. |
| Part 1a (Monotherapy Dose Escalation) | EXPERIMENTAL | 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. |
| Part 1b (Monotherapy Safety Expansion) | EXPERIMENTAL | 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. |
| Part 1c (Additional Monotherapy Safety Expansion) | EXPERIMENTAL | 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. |
| Part 1d (Additional Monotherapy Safety Expansion in R/R CLL/SLL) | EXPERIMENTAL | Participants with R/R CLL/SLL will be enrolled at selected RDFE(s) to generate additional safety and efficacy data for tacabrutideg. |
| Part 1e (Japan-only Cohort) | EXPERIMENTAL | 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. |
| Part 1f (Additional Monotherapy Safety Expansion in BTKi Naive B-Cell Malignancies) | EXPERIMENTAL | 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. |
| Phase 2 (Monotherapy Expansion) | EXPERIMENTAL | 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. |
| Name | Type | Description |
|---|---|---|
| Tacabrutideg | DRUG | Tacabrutideg will be administered orally |
| Pirtobrutinib | DRUG | Pirtobrutinib will be administered orally |
| BGB-16673 | DRUG | Administered orally |
| Bendamustine | DRUG | Administered intravenously |
| Rituximab | DRUG | Administered intravenously |
| Methylprednisolone | DRUG | Administered intravenously |
| Chlorambucil | DRUG | Administered orally |
| Obinutuzumab | DRUG | Administered intravenously |
| Idelalisib | DRUG | Administered orally |
| Venetoclax | DRUG | Administered orally |
| Placebo | DRUG | Administered orally |
| Sonrotoclax | DRUG | Administered orally |
| Zanubrutinib | DRUG | Administered orally |
| Mosunetuzumab | DRUG | Administered subcutaneously |
| Glofitamab | DRUG | Administered intravenously |
Inclusion Criteria: * Confirmed diagnosis of CLL or SLL, requiring treatment, based on 2018 iwCLL criteria * Previously received treatment for CLL/SLL with a covalent Bruton tyrosine kinase inhibitor (cBTKi). Patients should have disease relapsed after or refractory to at least 1 line of therapy in...
Tacabrutideg is an investigational small molecule drug being developed by BeOne Medicines Ltd. for B-cell malignancies and chronic spontaneous urticaria. It is designed to target the BCL2 protein. The drug is currently in clinical development, with trials enrolling patients with chronic lymphocytic leukemia, small lymphocytic lymphoma, and chronic spontaneous urticaria.
Tacabrutideg is being studied for the treatment of chronic lymphocytic leukemia and small lymphocytic lymphoma, including relapsed or refractory cases. It is also being evaluated in chronic spontaneous urticaria. The drug is investigational and has not been approved for any indication.
Tacabrutideg targets BCL2, a protein involved in regulating cell survival. By binding to BCL2, the drug is designed to promote apoptosis in malignant B cells. This mechanism is being explored in B-cell malignancies such as chronic lymphocytic leukemia and small lymphocytic lymphoma.
Tacabrutideg is being developed by BeOne Medicines Ltd., which trades under the ticker ONC. The company is running multiple clinical trials of the drug across oncology and immunology indications.
Tacabrutideg is in Phase 1 and Phase 3 clinical development. Three active trials are ongoing, including a Phase 1 study in chronic spontaneous urticaria and two Phase 3 studies in chronic lymphocytic leukemia and small lymphocytic lymphoma. The drug is investigational and not approved.
Tacabrutideg is being evaluated in three active trials: NCT07005713, a Phase 1 study in chronic spontaneous urticaria; NCT06973187, a Phase 3 study versus pirtobrutinib in relapsed or refractory CLL/SLL; and NCT06846671, a Phase 3 study in patients previously exposed to BTK and BCL2 inhibitors. Another Phase 3 trial, NCT06970743, is active but not recruiting.
Yes, Tacabrutideg is also known as BGB-16673. The alternative name [14C]-BGB-16673 refers to a radiolabeled version used in research. Both names refer to the same investigational BCL2-targeting small molecule developed by BeOne Medicines Ltd.