catadegbrutinib (BGB-16673) / BeOne Medicines - LARVOL DELTA

Diagnosis and Management of Waldenstrom's Macroglobulinemia (ICML 2025) - P2 | "New or emerging options for patients progressing on c-BTKi include pirtobrutinib, BGB-16673, venetoclax, and sonrotoclax...CXCR4 antagonists such as plerixafor or ulocuplumab can sensitize CXCR4Mut-expressing WM cells to ibrutinib [22-24]...6 BTK Mutations BTKCys481 is the binding site for covalent BTK inhibitors (cBTK-i), including ibrutinib, zanubrutinib, acalabrutinib, orelabrutinib and tirabrutinib...For symptomatic treatment-naïve patients, chemoimmunotherapy with bendamustine and rituximab (Benda-R), dexamethasone, rituximab, and cyclophosphamide (DRC), as well as cBTK-i can be considered...Additional options in second or later relapse include re-use of chemotherapy if a response lasted for > 3 years, alternative chemoimmunotherapy, nucleoside analogs, or everolimus [38]...Zanubrutinib in combination with ixazomib and dexamethasone (ZID) is being investigated in a study in China (NCT04463953) and has shown high levels of response activity and good..."

IO biomarker • Hematological Malignancies • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Waldenstrom Macroglobulinemia • BCLAF1 • CXCL12 • FOXO3 • IL10 • IL6 • IRAK4 • MYD88 • PLCG2 • SYK • TNFAIP3 • TRAF3IP2

The Optimal Management of Waldenström Macroglobulinemia (SOHO 2025) - "Standard treatment options include alkylating agents (eg, bend-amustine or cyclophosphamide) or proteasome inhibitors (eg, bortezomib, carfilzomib, or ixazomib) in combination with anti-CD20 monoclonal antibody rituximab, covalent Bruton tyrosine kinase (BKT) inhibitors (eg ibrutinib, acalabrutinib, or zanubrutinib), BCL2 antagonists (eg, venetoclax), and non-covalent BTK inhibitors (eg, pirtobrutinib) 13–23...The combination of bendamustine and rituximab showed superior progression-free survival (PFS) to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone in a study by the STiL group 13...The all-oral, non-chemo, fixed-duration combination of pirtobrutinib and venetoclax has shown promise in early relapse 29.Inlate relapse, multiple agents are under active development, including second-generation BCL2 antagonists (eg, sonrotoclax), BTK degraders (eg, BGB-16673 30, NX-5948), conjugated radioisotopes (eg, iopofosine I-131 31), antibody-drug conjugates..."

IO biomarker • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Hematological Malignancies • Indolent Lymphoma • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Marginal Zone Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Waldenstrom Macroglobulinemia • B2M • BCL2 • CXCR4 • MYD88 • TP53

Advances in the Management of Relapsed/Refractory CLL and Richter Transformation (ICML 2025) - P=N/A, P2, P3 | "BRUIN CLL-321 is a phase 3, registrational study that evaluated pirtobrutinib compared to the investigator's choice of idelalisib plus rituximab (IdelaR) or bendamustine plus rituximab (BR) [23]...Nemtabrutinib is now being evaluated in the registrational, phase 3 BELLWAVE-010 trial (NCT05947851) for patients with R/R CLL, comparing nemtabrutinib plus venetoclax to venetoclax plus rituximab...An ongoing, open-label, first-in-human phase 1/2 study is evaluating the BTK degrader BGB-16673 as monotherapy in patients with R/R CLL [27, 28]...NX-2127 is an investigational, first-in-class BTK degrader currently being evaluated in a phase 1 trial for patients with relapsed or refractory B-cell malignancies, CLL [29, 30]...NX-5948 is another investigational and more selective BTK degrader in an ongoing Phase 1a/1b clinical trial...This trial aims to establish lisaftoclax plus acalabrutinib as a potential alternative to venetoclax-based BTKi combination..."

IO biomarker • Acute Myelogenous Leukemia • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome • Small Lymphocytic Lymphoma • BCL2L1 • TP53

BeOne Medicines Announces Second Quarter 2025 Financial Results and Business Updates (Businesswire) - "BGB-16673 (BTK CDAC): Achieved first subject enrolled for global Phase 3 BGB-16673-302 trial for the treatment of R/R CLL. Achieved first subject enrolled for China Phase 3 BGB-16673-303 trial for the treatment of R/R/ CLL. Initiated enrollment of potentially registration enabling Phase 2 trial for the treatment of R/R WM. Tarlatamab (AMG 757): Achieved acceptance of BLA and priority review in China for the treatment of 3L+ small cell lung cancer (SCLC). Achieved acceptance of BLA in China for the treatment of 2L SCLC."

China filing • Priority review • Trial status • Chronic Lymphocytic Leukemia • Small Cell Lung Cancer • Waldenstrom Macroglobulinemia

New Targets and Drugs on the Horizon in Chronic Lymphocytic Leukemia (SOHO 2025) - P1, P1/2 | "12 Treatment planning for patients with " double refractory " CLL — CLL that is resistant to a covalent BTKi and venetoclax — is a relatively novel but emerging scenario in the clinic...Noncovalent (Reversible) BTK Inhibitors In the BRUIN-321 phase 3 randomized trial of pirtobrutinib monotherapy versus the control arm of the investigator's choice between idealisib plus rituximab or bendamustine plus rituximab, pirtobrutinib had improved PFS (14 vs 8.7 months, Hazard ratio [HR] 0.54, P = 0.0002) and a superior time to next treatment or death compared to the control arm (24 vs 10.9 months, HR 0.37, P < 0.0001)...Nemtabrutinib is another noncovalent BTKi under clinical investigation, demonstrating an overall response rate (ORR) of 36.4% in CLL patients in the phase 1 study (n = 22 patients)...23,24 Thus far, data for three orally administered BTK degraders — NX-2127, NX-5948 and BGB-16673 23–25— have been presented, and there are ongoing clinical..."

IO biomarker • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Leukemia • Lymphoma • Oncology • CD20 • PRKCB • PRKCH • ROR1

Updated Efficacy and Safety of the Bruton Tyrosine Kinase Degrader BGB-16673 in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: Results From the Ongoing Phase 1 CaDAnCe-101 Study (IWCLL 2025) - No abstract available

Clinical • P1 data • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Small Lymphocytic Lymphoma • BTK

BeOne Medicines Receives PRIME Designation from the European Medicines Agency for BGB-16673 in Waldenstrom’s Macroglobulinemia (Yahoo Finance) - "BeOne Medicines Ltd...announced that the European Medicines Agency (EMA) has granted PRIority MEdicines (PRIME) designation to the Company’s investigational Bruton’s tyrosine kinase (BTK) degrader, BGB-16673, for the treatment of patients with Waldenstrom’s macroglobulinemia (WM) previously treated with a BTK inhibitor...In addition to the PRIME designation, the EMA’s Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion on the EU Orphan Drug Designation (ODD) application for BGB-16673 in WM. A final decision is anticipated in the coming weeks...The EMA’s CHMP granted PRIME designation to BGB-16673 based on data demonstrating its novel mechanism and anti-tumor activity in B-cell malignancies."

CHMP • European regulatory • Waldenstrom Macroglobulinemia

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) - "The activity did not differ from the BTK inhibitor zanubrutinib and, accordingly, was limited in cells resistant to ibrutinib (n. = 2), idelalisib (n...= 1), and copanlisib/venetoclax (n...Karpas1718, SSK41, VL51 and HC1 were exposed to BGB-16673 plus lenalidomide, selinexor, venetoclax, sonrotoclax (BGB-11417), bendamustine, tazemetostat and rituximab... Its ability to degrade BTK protein, combined with its synergistic effects with other targeted therapies, positions BGB-16673 as a promising candidate for further development in MZL patients. The 2nd generation BCL2 inhibitor sonrotoclax appears as another drug to be explored in the same patient populations, possibly combining the two molecules."

B Cell Lymphoma • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Oncology • BCL2L1 • CRBN • MCL1

CaDAnCe-303: A Study of BGB-16673 Compared to Investigator's Choice in Participants With Relapsed/Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Previously Exposed to Covalent Bruton Tyrosine Kinase (BTK) Inhibitors (clinicaltrials.gov) - P3 | N=150 | Recruiting | Sponsor: BeiGene | Not yet recruiting ➔ Recruiting

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

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple-Ascending Doses of BGB-16673 in Adults With Chronic Spontaneous Urticaria (clinicaltrials.gov) - P1 | N=27 | Recruiting | Sponsor: BeiGene | Not yet recruiting ➔ Recruiting

Enrollment open • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria

INTERNATIONAL OVERVIEW OF CHINESE NOVEL DRUGS IN INDOLENT LYMPHOMA (ICML 2025) - "China's groundbreaking advancements have been achieved in indolent lymphoma therapies, anchored by Zanubrutinib, a best-in-class BTK inhibitor. Key clinical trials (ALPINE, ROSEWOOD) demonstrate its superior progression-free survival in CLL/SLL and FL, supported by global expansion into over 70 markets. Beyond BTK inhibition, other novel drugs include BTK degrader (BGB-16673), BCL-2 inhibitor (Sonrotoclax), and CAR-T (Axi-cel and Rel-cel), positioning China at the forefront of indolent lymphoma research."

Chronic Lymphocytic Leukemia • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Oncology

MECHANISMS OF RESISTANCE TO SMALL MOLECULE INHIBITORS (ICML 2025) - "The relevant approved agents are: Ibrutinib, acalbrutinib and Zanubrutinib as covalent inhibitors, and Pirtobrutinib as a non-covalent inhibitor of BTK, Idelalisib as a PI3K inhibitor and Venetoclax as a BCL2 inhibitor. Although these pathway specific resistance mechanisms do not predict for intrinsic resistance to the other drug class (BTK vs. BCL2 inhibitors), early single-cell data suggest that "double class" resistant disease can involve both compound mutant clones (harboring both BTK and BCL2) mutations, or heterogeneous multi-clonal mechanisms. The mechanisms of acquired resistance to currently approved agents have significant implications both for clinical management and treatment sequencing decisions and the potential utility of novel agents targeting these same pathways (such as BTK-degraders BGB-16673 and NX-5984 and the BCL2 inhibitor sonrotoclax)."

IO biomarker • Chronic Lymphocytic Leukemia • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Richter's Syndrome • Waldenstrom Macroglobulinemia • BCL2L1 • MCL1

UPDATED EFFICACY & SAFETY OF BTK DEGRADER BGB-16673 IN PATIENTS (PTS) WITH RELAPSED/REFRACTORY WALDENSTRÖM MACROGLOBULINEMIA (R/R WM): ONGOING PHASE 1 CaDAnCe-101 RESULTS (ICML 2025) - P1/2 | "Updated data from this ongoing study show that the novel BTK degrader BGB-16673 is tolerable and has substantial antitumor activity in heavily pretreated BTKi–exposed pts with WM, including those with BTK, CXCR4, and TP53 mutations."

Clinical • IO biomarker • P1 data • Lymphoma • Lymphoplasmacytic Lymphoma • Waldenstrom Macroglobulinemia • CXCR4 • MYD88 • TP53

UPDATED EFFICACY/SAFETY OF THE BRUTON TYROSINE KINASE (BTK) DEGRADER BGB-16673 IN RELAPSED/REFRACTORY (R/R) CLL/SLL: RESULTS FROM THE ONGOING PHASE 1 CaDAnCe-101 STUDY (ICML 2025) - P1/2 | "The novel BTK degrader BGB-16673 has a tolerable safety profile, and robust and deepening responses in pts with heavily pretreated R/R CLL/SLL, including pts with prior BTKis and BTKi mutations."

Clinical • IO biomarker • P1 data • Chronic Lymphocytic Leukemia • Lymphoma • Small Lymphocytic Lymphoma • BTK • IGH • TP53

UPDATED EFFICACY/SAFETY OF BRUTON TYROSINE KINASE DEGRADER BGB-16673 IN PATIENTS WITH RELAPSED/REFRACTORY INDOLENT NHL: ONGOING PHASE 1 CaDAnCe-101 RESULTS (ICML 2025) - P1/2 | "These data demonstrate that the novel BTK degrader BGB-16673 is tolerable and shows durable responses in heavily pretreated patients with FL and, particularly, MZL, including those receiving a prior BTKi. CaDAnCe-101 enrollment continues for patients with FL and MZL."

Clinical • P1 data • Follicular Lymphoma • Indolent Lymphoma • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • BTK

UPDATED EFFICACY AND SAFETY OF THE BRUTON TYROSINE KINASE (BTK) DEGRADER BGB-16673 IN PATIENTS (PTS) WITH RELAPSED OR REFRACTORY (R/R) CLL/SLL: RESULTS FROM THE ONGOING PHASE (PH) 1 CADANCE-101 STUDY (EHA 2025) - P1/2 | "Data from this ongoing study demonstrate that the novel BTK degrader BGB-16673 has a tolerable safety profile and shows robust and deepening responses in pts with heavily pretreated R/R CLL/SLL, including those with prior BTKi tx and BTKi mutations."

Clinical • IO biomarker • Atrial Fibrillation • Cardiovascular • Chronic Lymphocytic Leukemia • CNS Disorders • Fatigue • Febrile Neutropenia • Hematological Disorders • Hypertension • Infectious Disease • Neutropenia • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases • Septic Shock • Small Lymphocytic Lymphoma • Subarachnoid Hemorrhage • BTK • IGH • TP53

UPDATED EFFICACY & SAFETY OF THE BRUTON TYROSINE KINASE (BTK) DEGRADER BGB-16673 IN PATIENTS WITH RELAPSED/REFRACTORY WALDENSTRÖM MACROGLOBULINEMIA (WM): ONGOING PHASE (PH) 1 CADANCE-101 STUDY RESULTS (EHA 2025) - P1/2 | "Data from this ongoing study demonstrate that the novel BTK degrader BGB-16673 was well tolerated and continued to show substantial antitumor activity in pts with heavily pretreated BTK inhibitor-exposed R/R WM, including those with BTK, CXCR4, and TP53 mutations."

Clinical • IO biomarker • Anemia • Atrial Fibrillation • Cardiovascular • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Hypertension • Infectious Disease • Lymphoma • Lymphoplasmacytic Lymphoma • Neutropenia • Oncology • Respiratory Diseases • Septic Shock • Thrombocytopenia • Waldenstrom Macroglobulinemia • BTK • CXCR4 • MYD88 • TP53

BTK-A428D IS A CROSS-RESISTANT MUTATION TO BOTH BTK INHIBITORS AND DEGRADERS (EHA 2025) - "BTK-A428D is a mutation that exhibits cross-resistance to multiple BTK degraders (BGB-16673, NX-2127, NX-5948, Abbv Compound 1) and inhibitors (ibrutinib, acalabrutinib, zanubrutinib, and pirtobrutinib) both in vitro and in vivo, as supported by evidence from multiple aspects. In the future, BTK-A428D mutated cancer cells may be treated by other targeted therapies."

Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • PLCG2

Diagnosis and Management of Waldenstrom's Macroglobulinemia. (PubMed, Hematol Oncol) - "The cBTK-i zanubrutinib shows greater response activity and/or improved progression-free survival in WM patients with wild-type MYD88, mutated CXCR4, or altered TP53. New or emerging options for patients progressing on c-BTKi include pirtobrutinib, BGB-16673, venetoclax, and sonrotoclax. Combinations of BTK inhibitors with chemoimmunotherapy and BCL2 antagonists have advanced. Algorithms for patients with treatment-naïve and previously treated WM based on genomics, disease characteristics, and co-morbidities are discussed."

IO biomarker • Journal • Review • Hematological Disorders • Hematological Malignancies • Lymphoma • Lymphoplasmacytic Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Waldenstrom Macroglobulinemia • BCL2 • CXCR4 • MYD88 • TP53

Robust Early Results in CLL and WM with Potentially First-in-Class BTK Degrader (Businesswire) - P1 | N=621 | CaDAnCe-101 (NCT05006716) | Sponsor: BeiGene | "As the most clinically advanced BTK degrader, BGB-16673 continues to show potential in patients with various hematological malignancies. Updated data from the ongoing Phase 1 CaDAnCe-101 study of BGB-16673 in R/R CLL/SLL and R/R Waldenström macroglobulinemia (WM) showed substantial antitumor activity and a tolerable safety profile across heavily pretreated populations...R/R CLL/SLL (Oral Presentation S158):ORR: 84.8% across all dose levels and 93.8% at the recommended phase 2 dose of 200mg; R/R Waldenström Macroglobulinemia (Oral Presentation S231):ORR: 84.4%; major response rate: 75.0%; very good partial response rate (VGPR): 31.3%"

P1 data • Chronic Lymphocytic Leukemia • Small Lymphocytic Lymphoma • Waldenstrom Macroglobulinemia

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple-Ascending Doses of BGB-16673 in Adults With Chronic Spontaneous Urticaria (clinicaltrials.gov) - P1 | N=27 | Not yet recruiting | Sponsor: BeiGene

New P1 trial • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria

BeiGene Showcases Strength of Hematology Portfolio at EHA 2025 with New Data Highlighting BRUKINSA’s Leadership and Next-Generation Innovation (BeiGene Press Release) - "BeiGene, Ltd...announced it will share data across a range of hematologic malignancies at the European Hematology Association (EHA) Congress in Milan, Italy, June 12–15. BeiGene has 31 abstracts accepted at EHA 2025, with four selected for oral presentations, featuring data from its best-in-class Bruton’s tyrosine kinase (BTK) inhibitor BRUKINSA (zanubrutinib) and its investigational pipeline assets – a next-generation BCL2 inhibitor, sonrotoclax, and BTK protein degrader, BGB-16673."

Clinical data • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Mantle Cell Lymphoma • Small Lymphocytic Lymphoma • Waldenstrom Macroglobulinemia

BeiGene Announces First Quarter 2025 Financial Results and Business Updates (Businesswire) - "Sonrotoclax (BCL2 inhibitor): Continued enrollment of global Phase 2 trial for the treatment of Waldenström’s macroglobulinemia. Sonrotoclax BGB-11417-202: Filed in China for the treatment of relapsed/refractory (R/R) CLL. Sonrotoclax CELESTIAL-RR MCL BGB-11417-302: Achieved first subject enrolled for Phase 3 trial for the treatment of R/R MCL. Sonrotoclax CELESTIAL-TN CLL BGB-11417-301: Achieved last subject enrolled for Phase 3 trial for the treatment of treatment-naïve (TN) CLL. BGB-16673: Initiated Phase 3 trial compared to physician’s choice (IR/VR/BR) for treatment of R/R CLL."

China filing • Enrollment status • Trial status • Chronic Lymphocytic Leukemia • Waldenstrom Macroglobulinemia

A Study of BGB-16673 Compared to Investigator's Choice in Participants With Relapsed/Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Previously Exposed to Covalent BTK Inhibitors (clinicaltrials.gov) - P3 | N=150 | Not yet recruiting | Sponsor: BeiGene

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

A Study to Evaluate the Safety and Efficacy of BGB-16673 Compared to Pirtobrutinib in Adults With Relapsed/Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma (clinicaltrials.gov) - P3 | N=500 | Not yet recruiting | Sponsor: BeiGene

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