sonrotoclax (BGB-11417) / BeOne Medicines - LARVOL DELTA

Updated Interim Results of Sonrotoclax + Dexamethasone in Patients With t(11; 14)-Positive Relapsed/Refractory Multiple Myeloma (R/R MM): An All-Oral Treatment (IMS 2025) - P1/2 | "Sonrotoclax (sonro; BGB-11417), a next-generation BCL2 inhibitor, is a more selective and pharmacologically potent inhibitor of BCL2 than venetoclax, with a shorter half-life and no drug accumulation. This ongoing study showed that the all-oral combination of sonro + dex is tolerable, with low rates of infection and hematologic toxicity, and promising efficacy, with an ORR of 81% in the 640-mg cohort, in this t(11; 14)-positive R/R MM population. Additional tx combinations with sonro are being investigated."

Clinical • CNS Disorders • Fatigue • Hematological Malignancies • Infectious Disease • Insomnia • Multiple Myeloma • Pancreatic Cancer • Pneumonia • Respiratory Diseases • Respiratory Syncytial Virus Infections • Sleep Disorder • Solid Tumor

Sonrotoclax (BGB-11417) monotherapy in patients with Relapsed/Refractory (R/R) Mantle Cell Lymphoma (MCL) previously treated with a bruton tyrosine kinase (BTK) inhibitor: Early results from A phase 1/2 study (ASH 2025) - P1/2 | "Sonrotoclax (BGB-11417), a next-generation B-cell lymphoma 2 (BCL2) inhibitor, is a more selective and pharmacologically potent inhibitorof BCL2 than venetoclax, with a shorter half-life and no drug accumulation. Preliminary results indicate that once daily sonrotoclax 320 mg monotherapy is welltolerated in patients with R/R MCL previously treated with a BTK inhibitor. Clinically meaningful benefits,including median DOR of 15.8 months, were seen in patients with high unmet needs and advanced,aggressive disease. These results support sonrotoclax as a promising treatment option for patients withR/R MCL."

Clinical • Monotherapy • P1/2 data • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Hematological Disorders • Infectious Disease • Lymphoma • Mantle Cell Lymphoma • Neutropenia • Pneumonia • Respiratory Diseases

Novel therapeutic strategies targeting resistance mechanisms in hematologic malignancies: from BCL2 inhibition to immunomodulatory approaches. (PubMed, Front Pharmacol) - "Main Findings: BCL2 inhibitors like venetoclax have achieved high response rates (ORR >70%) in CLL and AML but face resistance via MCL1/BCL-XL upregulation. Next-generation agents (e.g., sonrotoclax) and combinations address this...These strategies represent a paradigm shift toward precision medicine, but challenges like toxicity and biomarker-driven resistance persist. Future directions include AI-guided predictions and novel degraders like proteolysis-targeting chimeras (PROTACs)."

IO biomarker • Journal • Review • Acute Myelogenous Leukemia • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Oncology • Targeted Protein Degradation • BCL2L1 • MCL1

Initial phase 1b/2 study results with sonrotoclax (BGB-11417) in combination with carfilzomib and dexamethasone in patients with t(11; 14)-positive relapsed/refractory multiple myeloma (ASH 2025) - P1/2 | "Sonrotoclax (BGB-11417), a next-generation BCL2 inhibitor, is a more selective and pharmacologically potent inhibitor ofBCL2 than venetoclax, with a shorter half-life and no drug accumulation. Sonrotoclax + K + dex combination therapy demonstrated a tolerable safety profile andencouraging antimyeloma activity, with an 84% ORR and a 32% CR/sCR rate in heavily pretreated patientswith t(11; 14)-positive R/R MM. Enrollment in BGB-11417-105 is ongoing, and additional treatmentcombinations with sonrotoclax are being investigated."

Clinical • Combination therapy • P1/2 data • Acute Kidney Injury • Back Pain • Cardiovascular • CNS Disorders • Hematological Disorders • Hematological Malignancies • Hypertension • Infectious Disease • Insomnia • Multiple Myeloma • Musculoskeletal Pain • Nephrology • Pneumonia • Renal Disease • Respiratory Diseases • Sleep Disorder • Thrombocytopenia

A Study to Investigate the Relative Bioavailability and Food Effect of a Fixed-Dose Combination Tablet Containing Zanubrutinib and Sonrotoclax (BG-71332) in Healthy Adults (clinicaltrials.gov) - P1 | N=24 | Active, not recruiting | Sponsor: BeOne Medicines | Recruiting ➔ Active, not recruiting

Enrollment closed

CELESTIAL-TNCLL: An ongoing, open-label, multiregional, phase 3 study of sonrotoclax (BGB-11417) + zanubrutinib vs venetoclax + obinutuzumab for treatment-naïve (TN) CLL. (ASCO 2024) - P3 | "Background: The combination of venetoclax (ven), the first-generation BCL2 inhibitor, and ibrutinib, a BTK inhibitor, has demonstrated efficacy in patients with CLL (Wierda et al. Other secondary endpoints include PFS as assessed by investigator (INV); CRR by INV; rate of uMRD4 based on flow cytometry; overall response rate by IRC and INV; duration of response by IRC and INV; patient-reported outcomes; and safety and tolerability. Recruitment is ongoing."

Clinical • IO biomarker • P3 data • Chronic Lymphocytic Leukemia • Hematological Disorders • Neutropenia • TP53

Sonic: Escalated inpatient ramp-up of sonrotoclax in CLL/SLL and MCL (ASH 2025) - P2 | "Sonrotoclax (BGB-11417) is apromising next generation Bcl-2 inhibitor with better potency and specificity than venetoclax, a firstgeneration Bcl-2 inhibitor, in pre-clinical studies...Patients with a prior othermalignancy within the past 2 years are excluded.Objectives:Primary Objectives:To examine the safety and tolerability of an escalated ramp-up of sonrotoclax (BGB-11417) followinginitial debulking with zanubrutinib or rituximab in patients with treatment-naïve or R/R CLL/SLL andpatients with R/R MCL.To assess safety by measuring the frequency of adverse events (AEs), including episodes of laboratoryand clinical TLS.To evaluate the feasibility of reaching a target dose of sonrotoclax 320mg daily on day 12 +/- 2 daysfollowing a 4-day inpatient ramp-up of sonrotoclax.Secondary Objective:To estimate the efficacy of an escalated ramp-up of sonrotoclax followed by 1 year of combinationtherapy (with either zanubrutinib or rituximab) by assessing the overall..."

Clinical • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Richter's Syndrome • Small Lymphocytic Lymphoma

MRD-guided therapy of sonrotoclax (BGB-11417) + obinutuzumab (O) in patients with treatment-naive CLL: Initial results from an ongoing phase 1/1b study, BGB-11417-101 (ASH 2025) - P1 | "Introduction: The first-generation BCL2 inhibitor, venetoclax, is an effective treatment for CLL/SLL, but itsusage may be limited by toxicity. Sonrotoclax + obinutuzumab was generally well tolerated in patients with TN CLL/SLL, withno sonrotoclax discontinuations or deaths due to TEAEs. No laboratory or clinical TLS events occurredduring sonrotoclax ramp-up. Encouraging antitumor activity was observed with sonrotoclax 320 mg."

Clinical • IO biomarker • P1 data • Chronic Lymphocytic Leukemia • Genito-urinary Cancer • Hematological Malignancies • Neutropenia • Prostate Cancer • Richter's Syndrome • Solid Tumor • Thrombocytopenia • IGH

An Open-Label, Single-Arm Study of Sonrotoclax Plus Zanubrutinib in Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) Without Disease Progression After First-Line BTK Inhibitor Therapy. (ChiCTR) - P=N/A | N=50 | Not yet recruiting | Sponsor: The First Affiliated Hospital of Soochow University; The First Affiliated Hospital of Soochow University

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

A Phase 1 Study with the Novel B-Cell Lymphoma 2 (Bcl-2) Inhibitor Bgb-11417 As Monotherapy or in Combination with Zanubrutinib (ZANU) in Patients (Pts) with CLL/SLL: Preliminary Data (ASH 2022) - P1a/1b | "Background/introduction: The effectiveness of Bcl-2 inhibitors as a treatment for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) was established by the approval of venetoclax in pts with CLL/SLL across all lines of therapy. These preliminary data show BGB-11417, alone or in combination with ZANU, was well-tolerated in most patients. Grade ≥3 neutropenia was uncommon and manageable. Efficacy is supported by the rapid reduction in ALC during ramp-up, and early response data are promising."

Clinical • Combination therapy • IO biomarker • Monotherapy • P1 data • Chronic Lymphocytic Leukemia • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome • Small Lymphocytic Lymphoma • Waldenstrom Macroglobulinemia

PRELIMINARY SAFETY AND ANTILEUKEMIC ACTIVITY OF SONROTOCLAX (BGB-11417), A POTENT AND SELECTIVE BCL2 INHIBITOR, IN PATIENTS WITH RELAPSED/REFRACTORY ACUTE MYELOID LEUKEMIA (EHA 2024) - P1/2, P1b/2 | "Although treatment with the BCL2 inhibitor venetoclax has improved outcomes in some patients (pts) withnewly diagnosed acute myeloid leukemia (AML), it is not approved in relapsed/refractory (R/R) AML. In this ongoing dose escalation phase 1b/2 trial, sonrotoclax + azacitidine was generally well tolerated. Thiscombination demonstrated promising antileukemic activity in pts with R/R AML including in the lowest dosecohorts. Further evaluation in pts with R/R AML is ongoing."

Clinical • IO biomarker • Acute Myelogenous Leukemia • Anemia • Bone Marrow Transplantation • Febrile Neutropenia • Infectious Disease • Lymphoma • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Neutropenia • Thrombocytopenia • Transplantation

Combination Treatment with Sonrotoclax (BGB-11417), a Second-Generation BCL2 Inhibitor, and Zanubrutinib, a Bruton Tyrosine Kinase (BTK) Inhibitor, Is Well Tolerated and Achieves Deep Responses in Patients with Treatment-Naïve Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (TN-CLL/SLL): Data from an Ongoing Phase 1/2 Study (ASH 2023) - P1 | "The combination of venetoclax, a BCL2 inhibitor, and ibrutinib, a BTK inhibitor, is an effective treatment for CLL/SLL. Sonrotoclax (160 mg and 320 mg) in combination with zanubrutinib was well tolerated in patients with TN CLL/SLL. Only one patient discontinued treatment and three patients had dosage reductions. No TLS was seen with either ramp-up schedule."

Clinical • P1/2 data • Atrial Fibrillation • Cardiovascular • Chronic Lymphocytic Leukemia • CNS Disorders • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Novel Coronavirus Disease • Oncology • Small Lymphocytic Lymphoma

Sonrotoclax and Zanubrutinib as Frontline Treatment for CLL Demonstrates High MRD Clearance Rates with Good Tolerability: Data from an Ongoing Phase 1/1b Study BGB-11417-101 (ASH 2024) - P1 | "Introduction : The combination of venetoclax, a BCL2 inhibitor, with ibrutinib, a BTK inhibitor, is effective in CLL/SLL, but their clinical use can be limited by toxicity. With a median follow-up of 18.3 mo, only 1 PFS event occurred in the 160-mg cohort, and none occurred in the 320-mg cohort. A registrational phase 3 study (CELESTIAL-TNCLL, BGB-11417-301) assessing this combination with sonrotoclax 320 mg is recruiting."

IO biomarker • P1 data • Chronic Lymphocytic Leukemia • CNS Disorders • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Neutropenia • Novel Coronavirus Disease • Oncology • IGH • TP53

COMBINATION TREATMENT WITH NOVEL BCL2 INHIBITOR SONROTOCLAX (BGB-11417) AND ZANUBRUTINIB INDUCES HIGH RATE OF COMPLETE REMISSION FOR PATIENTS WITH RELAPSED/REFRACTORY MANTLE CELL LYMPHOMA (EHA 2025) - P1, P3 | "The phase 3 SYMPATICO study showed that combination therapy with venetoclax, a BCL2 inhibitor (BCL2i), and ibrutinib, a Bruton tyrosine kinase inhibitor (BTKi), had efficacy in patients (pts) with relapsed/refractory (R/R) MCL; however, treatment intolerance may impact its use. Sonrotoclax + zanu combination therapy was well tolerated and demonstrated encouraging antitumor activity, with a CR rate of 62.2%, and responses in pts previously treated with a BTKi. A registrational phase 3 study (NCT06742996) further assessing this combination with sonrotoclax 320mg is recruiting."

Clinical • Atrial Fibrillation • Cardiovascular • CNS Disorders • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Mantle Cell Lymphoma • Myelodysplastic Syndrome • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Septic Shock

SAFETY AND EFFICACY RESULTS OF A PHASE 1 STUDY OF THE NOVEL BCL2 INHIBITOR SONROTOCLAX (BGB-11417) FOR RELAPSED/REFRACTORY WALDENSTRÖM'S MACROGLOBULINEMIA (EHA 2024) - P1 | "In previous studies, theBCL2 inhibitor venetoclax demonstrated antitumor activity in patients with WM (Castillo 2022), but it is notapproved for the treatment of this disease. Sonrotoclax monotherapy was well tolerated in patients with R/R WM, and the preliminary antitumor activity isencouraging in this heavily pretreated R/R WM population. Based on findings of this study, further evaluationof sonrotoclax monotherapy in patients with R/R WM is ongoing in a potentially pivotal phase 2 study."

Clinical • P1 data • Anemia • Cardiovascular • CNS Disorders • Dermatology • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Lymphoplasmacytic Lymphoma • Neutropenia • Novel Coronavirus Disease • Oncology • Pneumonia • Pruritus • Respiratory Diseases • Waldenstrom Macroglobulinemia

UPDATED INTERIM RESULTS OF SONROTOCLAX + DEXAMETHASONE IN PATIENTS WITH T(11; 14)-POSITIVE RELAPSED/REFRACTORY MULTIPLE MYELOMA: AN ALL-ORAL TREATMENT (EHA 2025) - P1/2 | "Sonrotoclax (BGB-11417), a next-generation BCL2 inhibitor, is a more selective and pharmacologically potent inhibitor of BCL2 than venetoclax, with a shorter half-life and no drug accumulation. The all-oral combination of sonrotoclax + dex continued to show a tolerable safety profile, with low rates of infection and hematologic toxicity, and promising efficacy, with an ORR of 81% in the 640-mg cohort, in this t(11; 14)-positive R/R MM population. The study is ongoing; additional tx combinations with sonrotoclax are being investigated."

Clinical • CNS Disorders • Fatigue • Hematological Malignancies • Infectious Disease • Insomnia • Multiple Myeloma • Oncology • Pancreatic Cancer • Pneumonia • Respiratory Diseases • Respiratory Syncytial Virus Infections • Sleep Disorder • Solid Tumor

SONROTOCLAX PLUS DEXAMETHASONE IS TOLERABLE AND DEMONSTRATES ANTIMYELOMA ACTIVITY IN PATIENTS WITH RELAPSED/REFRACTORY (R/R) MULTIPLE MYELOMA HARBORING T(11; 14) (EHA 2024) - P1/2 | "Background: BCL2 is an attractive therapeutic target in multiple myeloma (MM) with t(11; 14), in that MM cells are primedfor BCL2 and responsive to oral BCL2 inhibitors, such as venetoclax, a first-generation BCL2 inhibitor. With longer follow-up, sonrotoclax plus dexamethasone continues to demonstrate** a manageable safetyprofile, with low rates of hematologic toxicities and infections. The combination provided deep and durableresponses in this R/R population. The study is ongoing, and other combination treatments with sonrotoclax arebeing investigated."

Clinical • CNS Disorders • Fatigue • Gastrointestinal Cancer • Hematological Disorders • Hematological Malignancies • Hepatocellular Cancer • Hepatology • Infectious Disease • Insomnia • Liver Failure • Multiple Myeloma • Neutropenia • Novel Coronavirus Disease • Oncology • Pancreatic Cancer • Sleep Disorder • Solid Tumor • Thrombocytopenia

Sonrotoclax (BGB-11417) in Combination with Dexamethasone for the Treatment of Relapsed/Refractory Multiple Myeloma with t(11; 14): Safety, Efficacy, and Determination of Recommended Phase 2 Dose (ASH 2023) - P1/2 | "In patients with relapsed/refractory (R/R) MM harboring t(11; 14) for whom multiple prior lines of therapy failed, single-agent venetoclax, a first generation BCL2 inhibitor, demonstrated antimyeloma activity (Kumar S, et al. Sonrotoclax plus dexamethasone was generally well tolerated in patients with R/R MM harboring t(11; 14) at doses up to 640 mg, and initial safety and efficacy results are promising. The SMC has recommended 640 mg in combination with dexamethasone as the RP2D. Recruitment is ongoing for the sonrotoclax in combination with dexamethasone and carfilzomib dose-finding arms and the sonrotoclax plus dexamethasone indication expansion cohort."

Clinical • Combination therapy • IO biomarker • P2 data • B Cell Lymphoma • Cataract • CNS Disorders • Fatigue • Hematological Malignancies • Infectious Disease • Insomnia • Lymphoma • Multiple Myeloma • Musculoskeletal Pain • Oncology • Ophthalmology • Pain • Retinal Disorders • Sleep Disorder

Preliminary Safety of a Bcl-2 Inhibitor, Bgb-11417, in Patients with Relapsed/Refractory Multiple Myeloma Harboring t(11,14): A Non-Randomized, Open-Label, Phase 1b/2 Study (ASH 2022) - P1b/2 | "Compared to venetoclax, BGB-11417 is a more potent (>10 fold in biochemical assays) and highly selective Bcl-2 inhibitor.The ongoing BGB-11417-105 trial (NCT04973605) is a phase 1b/2 study determining the safety and efficacy of BGB-11417 as monotherapy, in combination with dexamethasone, or with dexamethasone plus carfilzomib in patients with t(11; 14) positive R/R MM. BGB-11417 in combination with dexamethasone was generally well tolerated in patients with R/R MM harboring t(11; 14) at doses up to 640 mg. Efficacy data are forthcoming. Recruitment is ongoing in the US, Australia, and New Zealand; the BGB-11417, dexamethasone, and carfilzomib combination arm will open in the future."

Clinical • P1/2 data • Back Pain • CNS Disorders • Fatigue • Hematological Malignancies • Immune Modulation • Infectious Disease • Inflammation • Insomnia • Lymphoma • Multiple Myeloma • Musculoskeletal Pain • Novel Coronavirus Disease • Oncology • Pain • Sleep Disorder

BGB-11417-302, A PHASE 3, RANDOMIZED, DOUBLE-BLIND STUDY OF SONROTOCLAX (BGB-11417) + ZANUBRUTINIB VERSUS PLACEBO + ZANUBRUTINIB IN RELAPSED/REFRACTORY MANTLE CELL LYMPHOMA (ICML 2025) - P1, P3 | "Inhibition of B-cell lymphoma 2 (BCL2) and Bruton tyrosine kinase (BTK) with venetoclax + ibrutinib, respectively, has demonstrated efficacy in patients with relapsed or refractory MCL; however, use of this regimen can be limited by toxicity and development of treatment resistance. Secondary endpoints include overall survival, PFS (assessed by investigator), overall response rate, complete response rate, duration of response, and safety/tolerability. Recruitment is ongoing."

Clinical • P3 data • B Cell Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell 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) - P1/2 | "Sonrotoclax (sonro; BGB-11417), a next-generation BCL2 inhibitor, is a more selective and pharmacologically potent inhibitor of BCL2 than venetoclax, with a shorter half-life and no drug accumulation. This ongoing study showed that the all-oral combination of sonro + dex is tolerable, with low rates of infection and hematologic toxicity, and promising efficacy, with an ORR of 81% in the 640-mg cohort, in this t(11; 14)-positive R/R MM population. Additional tx combinations with sonro are being investigated."

Clinical • Hematological Malignancies • Lymphoma • Multiple Myeloma • Oncology

Sonrotoclax Plus Zanubrutinib in Patients With Relapsed/Refractory Mantle Cell Lymphoma Planned for Standard of Care CAR-T Cell Therapy (clinicaltrials.gov) - P2 | N=40 | Not yet recruiting | Sponsor: Canadian Cancer Trials Group

New P2 trial • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology • BCL2

Sonrotoclax Plus Dexamethasone With or Without Daratumumab Regimen in Patients With t(11;14) Primary AL Amyloidosis (clinicaltrials.gov) - P2 | N=39 | Not yet recruiting | Sponsor: Peking University People's Hospital

New P2 trial • Amyloidosis • BCL2

Sonrotoclax: Regulatory approval in US for r/r MCL in H1 2026 (BeOne Medicines, 44th Annual J.P. Morgan Healthcare Conference)

FDA approval • Hematological Malignancies • Mantle Cell Lymphoma • Oncology

Sonrotoclax: Regulatory approval in US for r/r MCL in H1 2026 (BeOne Medicines, 44th Annual J.P. Morgan Healthcare Conference)

FDA approval • Hematological Malignancies • Mantle Cell Lymphoma • Oncology