Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Tacabrutideg · 4 trials · 13 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 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 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: Tacabrutideg monotherapy | EXPERIMENTAL | Participants will receive tacabrutideg 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 idelalisib plus rituximab for CLL only or bendamustine plus rituximab, or venetoclax plus rituximab retreatment. |
| 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. |
| 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 |
| Bendamustine | DRUG | Administered intravenously |
| Idelalisib | DRUG | Administered orally |
| Rituximab | DRUG | Administered intravenously |
| Venetoclax | DRUG | Administered orally |
| Sonrotoclax | DRUG | Administered orally |
| Zanubrutinib | DRUG | Administered orally |
| Mosunetuzumab | DRUG | Administered subcutaneously |
| Glofitamab | DRUG | Administered intravenously |
| Obinutuzumab | 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 being developed for B-cell malignancies, including chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma, mantle cell lymphoma, follicular lymphoma, Waldenström macroglobulinemia, and diffuse large B-cell lymphoma. It is also studied in relapsed or refractory B-cell malignancies and in patients previously exposed to BTK and BCL2 inhibitors.
Tacabrutideg is being developed by BeOne Medicines Ltd., a company listed under the ticker ONC. The drug is currently in clinical development for B-cell malignancies and chronic lymphocytic leukemia.
Tacabrutideg is in Phase 1 clinical trials for B-cell malignancies, with two active Phase 1 studies recruiting participants. It is also being investigated in two Phase 3 trials for chronic lymphocytic leukemia and small lymphocytic lymphoma. The drug is investigational and not yet approved.
Tacabrutideg is being studied in several trials, including NCT05006716, a Phase 1 dose-escalation and expansion study in B-cell malignancies; NCT06634589, a Phase 1 combination study in relapsed or refractory B-cell malignancies; NCT06846671, a Phase 3 trial versus investigator's choice in CLL or SLL previously exposed to BTK and BCL2 inhibitors; and NCT06973187, a Phase 3 trial versus pirtobrutinib in relapsed or refractory CLL or SLL.
Yes, Tacabrutideg is also known as BGB-16673. Clinical trial records refer to the drug by both names, with BGB-16673 appearing in the titles of the studies. This alternative name is used interchangeably in research contexts.
The Tacabrutideg clinical program includes two Phase 1 trials with a combined enrollment of 725 participants, both randomized and controlled but not double-blind. The Phase 3 trials have enrollments of 250 and 500 participants respectively. All trials are actively recruiting and none have been completed.