sonrotoclax (BGB-11417) / BeiGene - LARVOL DELTA

Sonrotoclax (BGB–11417), A Novel BCL2 Inhibitor, Plus Zanubrutinib (Zanu) Demonstrates Deep and Durable Responses in Relapsed/Refractory CLL/SLL: Updated Phase 1 Results (ICML 2025) - No abstract available

P1 data • Lymphoma • Small Lymphocytic Lymphoma

Combination Treatment With Novel BCL2 Inhibitor Sonrotoclax (BGB–11417) + Zanubrutinib Induces High Rate of Complete Remission in Relapsed/Refractory Mantle Cell Lymphoma (ICML 2025) - No abstract available

Clinical • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology

The BTK degrader BGB–16673 and the BCL2 inhibitor sonrotoclax shows anti–tumor activity as single agents and in combination in marginal zone lymphoma models (ICML 2025) - No abstract available

Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Oncology

Updated Interim Results of Sonrotoclax + Dexamethasone in Patients With t(11; 14)–Positive Relapsed/Refractory Multiple Myeloma (R/R MM): an All–Oral Treatment (ICML 2025) - No abstract available

Clinical • Hematological Malignancies • Lymphoma • Oncology

CLL-RT1 extension trial: Zanubrutinib, a BTK inhibitor, plus tislelizumab, a PD1 inhibitor, plus sonrotoclax, a BCL2 inhibitor, for treatment of Richter Transformation (ICML 2025) - No abstract available

Lymphoma • Richter's Syndrome

BGB–11417–302, A Phase 3, Randomized, Double–Blind Study of Sonrotoclax (BGB–11417) + Zanubrutinib Vs Placebo + Zanubrutinib in Relapsed/Refractory Mantle Cell Lymphoma (ICML 2025) - No abstract available

Clinical • P3 data • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology

Sonrotoclax (BGB-11417) synergistically amplifies the radiotherapy-elicited anti-tumor immune response. (PubMed, Cancer Lett) - "Further combination of sonrotoclax and radiotherapy plus anti-PD-L1 exerted the most significant anti-tumor effects. Overall, our study indicated that sonrotoclax enhanced the anti-tumor immune response of radiotherapy through non-apoptotic roles of BCL-2, and shed light on the further clinical evaluation of the triple combination therapy of sonrotoclax, radiotherapy and immunotherapy."

IO biomarker • Journal • Oncology • CD8 • GPX4 • GZMB

Sonrotoclax, Rituximab, and Zanubrutinib in Treating Participants With Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, and Mantle Cell Lymphoma (clinicaltrials.gov) - P2 | N=20 | Recruiting | Sponsor: Fred Hutchinson Cancer Center | Not yet recruiting ➔ Recruiting

Enrollment open • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

Profiling protein-protein interactions to predict sensitivity to drugs targeting BCL2 family members in lymphoma models (AACR 2025) - "Drug sensitivity parameters were integrated with protein data using Spearman Correlation and Multiple Linear Regression (MLR, Lasso). We exposed MCL (n=10, JVM2, REC1, JEKO1, UPN1, SP49, SP53, MAVER1, GRANTA519, Z138, MINO), MZL (n=6, VL51, SSK41, Karpas1718, HC1, HAIRM, ESKOL) cell lines and MZL models of secondary resistance (MZL-RES) to idelalisib (n=2), copanlisib (n=2), ibrutinib (n=2), venetoclax (n=1) and copanlisib/venetoclax (n=2), to BCL2i (venetoclax, sonrotoclax), BCL2/BCXLi (navitoclax), and MCL1i (S63845). Anti-apoptotic inhibitors show variable heterogeneous activity in MCL and MZL models, including those resistant to PI3Ki and BTKi, which could be predicted quantifying the BCL2-family members levels and interactions using the SPID. Such an approach might have a clinical potential to predict the sensitivity of patients with mature B cell lymphomas to this class of agents."

IO biomarker • Acute Myelogenous Leukemia • B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL2L1

A Study to Investigate Progression-Free Survival With Sonrotoclax Plus Obinutuzumab Or Sonrotoclax Plus Rituximab Compared With Venetoclax Plus Rituximab Treatment In Patients With Relapsed and/or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CELESTIAL-RRCLL) (clinicaltrials.gov) - P3 | N=630 | Not yet recruiting | Sponsor: BeiGene

New P3 trial • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

BeiGene's BCL-2 inhibitor to be included in priority review for two indications [Google translation] (Sina Corp) - "On April 17, the website of the Drug Review Center of the National Medical Products Administration (CDE) showed that BeiGene's...sonrotoclax tablets (sonrotoclax) are planned to be included in the priority review. It is suitable for the treatment of adult patients with mantle cell lymphoma (MCL) who have previously received anti-CD20 treatment and BTKi treatment, as well as adult patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) who have received previous treatment."

Priority review • Chronic Lymphocytic Leukemia • Mantle Cell Lymphoma • Small Lymphocytic Lymphoma

Study of BGB-11417 Monotherapy in Participants With Relapsed or Refractory Mantle Cell Lymphoma (clinicaltrials.gov) - P1/2 | N=126 | Active, not recruiting | Sponsor: BeiGene | Trial primary completion date: Apr 2025 ➔ Jul 2025

Trial primary completion date • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology • CD20

The BCL2 family: from apoptosis mechanisms to new advances in targeted therapy. (PubMed, Signal Transduct Target Ther) - "The first BCL2-selective BH3-mimetic, venetoclax, showed remarkable efficacy with manageable toxicities and has transformed the treatment of several hematologic malignancies. Following its success, several chemically similar BCL2 inhibitors such as sonrotoclax and lisaftoclax are currently under clinical evaluation, alone and in combination...Tumor-specific BCL-XL or MCL1 inhibition may be achieved by novel targeting approaches using PROTACs or selective drug delivery strategies and would be transformational in many subtypes of malignancy. Taken together, we envision that the targeting of BCL2 proteins, while already a success story of translational research, may in the foreseeable future have broader clinical applicability and improve the treatment of multiple diseases."

IO biomarker • Journal • Review • B Cell Lymphoma • Hematological Disorders • Lymphoma • Oncology • Targeted Protein Degradation • Thrombocytopenia • BCL2 • BCL2L1

BeiGene Announces Fourth Quarter and Full Year 2024 Financial Results and Business Updates (Businesswire) - "Anticipate FDA and EC approvals of BRUKINSA tablet formulation in the second half of 2025; Anticipate an interim analysis of progression-free survival for the Phase 3 MANGROVE study in TN mantle cell lymphoma (MCL) in the second half of 2025; and Anticipate completing enrollment for the relapsed/refractory (R/R) follicular lymphoma portion of the Phase 3 MAHOGANY study in the second half of 2025. Sonrotoclax: Planned data readouts in R/R CLL and R/R MCL Phase 2 trials and potential accelerated approval submissions in the second half of 2025...Anticipate enrolling first subjects in global Phase 3 trials in R/R CLL and R/R MCL in the first half of 2025."

Approval • Clinical data • Enrollment status • FDA filing • New P3 trial • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Small Lymphocytic Lymphoma

BGB-16673-104: A Study to Investigate Safety and Effectiveness of BGB-16673 in Combination With Other Agents in Participants With Relapsed or Refractory B-Cell Malignancies (clinicaltrials.gov) - P1/2 | N=80 | Recruiting | Sponsor: BeiGene | N=170 ➔ 80

Enrollment change • B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

BOSon: Zanubrutinib, Obinutuzumab, and Sonrotoclax in Previously Untreated Patients with CLL or SLL (clinicaltrials.gov) - P2 | N=40 | Not yet recruiting | Sponsor: Massachusetts General Hospital

New P2 trial • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

WAZABI: Study Evaluating the Efficacy and Tolerance of a Zanubrutinib and BGB-11417 Combination in Patients Previously Treated for Waldenström Macroglobulinemia (clinicaltrials.gov) - P2 | N=102 | Not yet recruiting | Sponsor: French Innovative Leukemia Organisation | Trial completion date: Mar 2031 ➔ Dec 2031 | Initiation date: Oct 2024 ➔ Jun 2025 | Trial primary completion date: Mar 2028 ➔ Dec 2028

Trial completion date • Trial initiation date • Trial primary completion date • Hematological Disorders • Hematological Malignancies • Lymphoma • Lymphoplasmacytic Lymphoma • Non-Hodgkin’s Lymphoma • Waldenstrom Macroglobulinemia

Zanubrutinib in Combination With Sonrotoclax for the Treatment of Underrepresented Ethnic and Racial Minorities With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1 | N=37 | Not yet recruiting | Sponsor: City of Hope Medical Center

New P1 trial • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Extranodal Marginal Zone Lymphoma • Follicular Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Nodal Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • Splenic Marginal Zone Lymphoma

Risk-stratified treatment of sonrotoclax with chemotherapy in newly diagnosed acute myeloid leukemia: a study protocol. (PubMed, Future Oncol) - P2 | "Acute myeloid leukemia (AML) treatment relied on anthracyclines and cytarabine based intensive chemotherapy. We hypothesize that the addition of sonrotoclax to intensive chemotherapy may enhance the treatment efficacy for AML without untoward toxicity. Here, we describe the rationale and design of a single-arm, multicenter, phase 2 study evaluating the efficacy and safety of sonrotoclax combined with chemotherapy as an induction therapy in newly diagnosed patients with AML who are fit for intensive chemotherapy, followed by stratified subsequent consolidation and maintenance treatment based on patients' ELN2022 at diagnosis and MRD results after induction.Clinical Trail Registration: NCT06497062."

IO biomarker • Journal • Acute Myelogenous Leukemia • B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Oncology

Sonrotoclax: Completion of enrollment of P3 CELESTIAL-TN trial (NCT06073821) for CLL in H1 2025 (BeiGene) - Q4 2024 Results

Enrollment status • Chronic Lymphocytic Leukemia • Hematological Malignancies • Oncology

BRAZAN Trial in Frontline MCL (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: Christine Ryan

New P2 trial • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology

A Study to Investigate the Efficacy and Safety of Sonrotoclax Plus Zanubrutinib Compared With Placebo Plus Zanubrutinib in Adults With Relapsed/Refractory Mantle Cell Lymphoma (clinicaltrials.gov) - P3 | N=300 | Recruiting | Sponsor: BeiGene | Not yet recruiting ➔ Recruiting

Enrollment open • B Cell Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Sonrotoclax + Zanubrutinib Has High uMRD Rates and Good Tolerability in Ongoing Phase 1/1b Study in Treatment-Naive CLL (JSMO 2025) - No abstract available

P1 data • Chronic Lymphocytic Leukemia • Oncology

Sonrotoclax, Rituximab, and Zanubrutinib in Treating Participants With Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, and Mantle Cell Lymphoma (clinicaltrials.gov) - P2 | N=20 | Not yet recruiting | Sponsor: Fred Hutchinson Cancer Center

New P2 trial • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

Study of BGB-11417 in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma (clinicaltrials.gov) - P2 | N=100 | Active, not recruiting | Sponsor: BeiGene | Trial primary completion date: Apr 2025 ➔ Jan 2025

Trial primary completion date • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma