catadegbrutinib (BGB-16673) / BeiGene - LARVOL DELTA

BGB-16673, a BTK Degrader, in Patients With R/R CLL/SLL: Preliminary Phase 1 Results from CaDAnCe-101 (BSH 2025) - No abstract available

Clinical • P1 data • Chronic Lymphocytic Leukemia • Small Lymphocytic Lymphoma

Effect of Phenytoin or Itraconazole on How BGB-16673 is Absorbed and Removed From the Body in Healthy Participants (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: BeiGene | Not yet recruiting ➔ Recruiting

Enrollment open

A Study of BGB-16673 Compared to Investigator's Choice in Participants With Chronic Lymphocytic Leukemia Previously Exposed to Both Bruton Tyrosine Kinase (BTK) and B-cell Leukemia/Lymphoma 2 Protein (BCL2) Inhibitors (clinicaltrials.gov) - P3 | N=250 | Recruiting | Sponsor: BeiGene | Not yet recruiting ➔ Recruiting

Enrollment open • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology

An oral BTK degrader TGRX-3911 overcomes resistance conferred by kinase-proficient and kinase-impaired mutations (AACR 2025) - "TGRX-3911 potently inhibited proliferation of TMD8 parental cells and those harboring knock-in BTK mutations that are resistant to currently approved ibrutinib, zanubrutinib and/or pirtobrutinib, including C481S, T474I, L528W, V416L, A428D, T474I/C481S, T474I/L528W and C481S/L528W (IC50 from 0.4 to 9.9 nM). Remarkably, TGRX-3911 potently inhibited the A428D mutant which is still resistant to current BTK degraders, NX-5948, BGB-16673 and ABBV-101...By eliminating both the catalytic and scaffold functions of BTK, TGRX-3911 has the potential to overcome clinical resistance which can hardly be achieved by conventional BTKi. The potential clinical application of TGRX-3911 for patients with B-cell malignancies is worth exploring."

B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD86 • PLCG2

The BTK degrader BGB-16673 shows anti-tumor activity in marginal zone lymphoma models (AACR 2025) - "Effect on cell viability was assessed by MTT assay after 5 days of exposure to increasing concentrations of compounds or DMSO (control) in MZL cell lines and in cell lines with secondary resistance to idelalisib (n.=2), copanlisib (n.=1), ibrutinib (n.=2), and copanlisib/venetoclax. Oxidative phosphorylation, commonly associated with resistance to multiple therapies, was repressed by BGB-16673 but upregulated by zanubrutinib.Conclusions. Its ability to degrade BTK protein and its antitumor activity position the BTK degrader BGB-16673 as a promising candidate for further development in MZL patients."

B Cell Lymphoma • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CRBN

Effect of Phenytoin or Itraconazole on How BGB-16673 is Absorbed and Removed From the Body in Healthy Participants (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: BeiGene

New P1 trial

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

Breakthroughs in treatment for hematological malignancies: latest updates on molecular glue, PROTACs and RNA degraders from ASH 2024. (PubMed, J Hematol Oncol) - "Currently, the main categories developed based on degraders include molecular glue (such as Cemsidomide, NX-5948), PROTACs (such as BGB-16673, AC-676, KT-333 ), and RNA degraders (such as SKY-1214). This correspondence summarizes the preclinical and clinical updates on degrader therapies presented at the ASH 2024 annual meeting."

Journal • Review • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Targeted Protein Degradation

BeiGene Announces Fourth Quarter and Full Year 2024 Financial Results and Business Updates (Businesswire) - "BGB-16673: Continued to enroll potentially registration enabling R/R CLL Phase 2 study with data readout expected in 2026...Anticipate initiation of Phase 3 trial in R/R CLL compared to physician’s choice in the first half of 2025; and Anticipate initiation of Phase 3 head-to-head trial against noncovalent BTK inhibitor pirtobrutinib in R/R CLL in the second half of 2025."

New P3 trial • P2 data • Chronic Lymphocytic Leukemia

A Study of BGB-16673 Compared to Investigator's Choice in Participants With Chronic Lymphocytic Leukemia Previously Exposed to Both Bruton Tyrosine Kinase (BTK) and B-cell Leukemia/Lymphoma 2 Protein (BCL2) Inhibitors (clinicaltrials.gov) - P3 | N=250 | Not yet recruiting | Sponsor: BeiGene

New P3 trial • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology

BGB-16673-102: Treatment of Chinese Participants With B-Cell Malignancies With BGB-16673, a Bruton Tyrosine Kinase-Targeted Protein-Degrader (clinicaltrials.gov) - P1/2 | N=127 | Recruiting | Sponsor: BeiGene | Trial completion date: Mar 2027 ➔ Sep 2027 | Trial primary completion date: Mar 2027 ➔ Feb 2026

Trial completion date • Trial primary completion date • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome • Small Lymphocytic Lymphoma • Waldenstrom Macroglobulinemia

A Study of How [14C]-BGB-16673 is Absorbed, Broken Down, and Removed From the Body After a Single Oral Dose in Healthy Participants (clinicaltrials.gov) - P1 | N=8 | Recruiting | Sponsor: BeiGene | Not yet recruiting ➔ Recruiting

Enrollment open

Bruton Tyrosine Kinase Degraders: Current Concepts. (PubMed, Am J Clin Oncol) - "While BTK inhibitors (BTKi), such as ibrutinib, have been effective, resistance-both intrinsic and acquired-poses a significant challenge, often associated with BTK mutations like C481S...Agents such as NRX-0492, BGB-16673, NX-5948, NX-2127, HZ-Q1060, ABBV-101, and AC676 have shown significant BTK degradation in preclinical and early clinical trials...These BTK degraders have demonstrated favorable safety profiles, with manageable adverse events, and offer a novel therapeutic avenue for patients with BTKi-resistant malignancies. As clinical trials progress, these degraders hold the potential to significantly enhance treatment outcomes, offering a new frontier in personalized cancer therapy."

Journal • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Targeted Protein Degradation • BTK

BTK Is the Target That Keeps on Giving: A Review of BTK-Degrader Drug Development, Clinical Data, and Future Directions in CLL. (PubMed, Cancers (Basel)) - "We focus on four agents which are under investigation in B-cell malignancies in early clinical trials: BGB-16673, NX-2127, NX-5948, and AC676. Further trials investigating these agents in combination with other targeted CLL agents may help to further understand their applicability. An effective, tolerable oral class of drugs would be invaluable in the treatment of patients with multiply relapsed CLL/SLL."

Clinical data • Journal • Review • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • Targeted Protein Degradation • BCL2

BTK Is the Target That Keeps on Giving: A Review of BTK-Degrader Drug Development, Clinical Data, and Future Directions in CLL (Multidisciplinary Digital Publishing Institute) - "Encouraging pre-clinical data show that this MOA allows BTK protein degraders to overcome common BTK mutations. We focus on four agents which are under investigation in B-cell malignancies in early clinical trials: BGB-16673, NX-2127, NX-5948, and AC676. Preliminary data suggest a comparable safety and toxicity profile between agents across this drug class with many patients on phase 1 trials deriving durable clinical benefit. Optimal sequencing of BTK degraders in the therapeutic landscape of CLL/SLL treatment is yet to be established."

Review • Chronic Lymphocytic Leukemia • Small Lymphocytic Lymphoma

CaDAnCe-101: A Dose-Escalation and Expansion Study of BGB-16673 in Participants With B-Cell Malignancies (clinicaltrials.gov) - P1/2 | N=621 | Recruiting | Sponsor: BeiGene | Trial completion date: Mar 2028 ➔ Dec 2028 | Trial primary completion date: Mar 2025 ➔ Dec 2025

Trial completion date • Trial primary completion date • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • Waldenstrom Macroglobulinemia

A Study of How [14C]-BGB-16673 is Absorbed, Broken Down, and Removed From the Body After a Single Oral Dose in Healthy Participants (clinicaltrials.gov) - P1 | N=8 | Not yet recruiting | Sponsor: BeiGene

New P1 trial

Bgb-16673, a Selective BTK Degrader, Exhibits Deeper Inhibition of Cancer Cell Signaling Pathways and Better Efficacy in MCL Models (ASH 2024) - P1/2 | "Over the past decade, the development and approval of covalent BTK inhibitors (cBTKis) like ibrutinib, acalabrutinib, and zanubrutinib, as well as the non-covalent BTK inhibitor (ncBTKi) pirtobrutinib, have marked substantial progress of targeting BTK in MCL. Results also support the combination of BGB-16673 with Bcl-2 inhibitors in MCL. These discoveries highlight the potential of BGB-16673 in treating MCL patients."

Clinical • IO biomarker • Chronic Lymphocytic Leukemia • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology

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=170 | Recruiting | Sponsor: BeiGene | Not yet recruiting ➔ Recruiting

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

CaDAnCe-101: A Dose-Escalation and Expansion Study of BGB-16673 in Participants With B-Cell Malignancies (clinicaltrials.gov) - P1/2 | N=621 | Recruiting | Sponsor: BeiGene | N=466 ➔ 621

Enrollment change • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • Waldenstrom Macroglobulinemia

Preliminary Efficacy and Safety of the Bruton Tyrosine Kinase Degrader BGB-16673 in Patients with Relapsed or Refractory (R/R) Indolent NHL: Results from the Phase 1 CaDAnCe-101 Study (ASH 2024) - P1/2 | "Responses were seen in patients previously treated with a cBTKi (2/4 in MZL and 0/1 in FL with prior cBTKi) and a ncBTKi (0/1 in MZL and 1/1 in FL with prior ncBTKi). Conclusions : Emerging data from this ongoing, first-in-human study demonstrate that the novel BTK degrader BGB-16673 has a tolerable safety profile and shows clinically meaningful, durable responses in heavily pretreated patients with FL and MZL, including those with prior BTK inhibitor treatment."

Clinical • IO biomarker • P1 data • Atrial Fibrillation • Cardiovascular • Fatigue • Febrile Neutropenia • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Hypertension • Indolent Lymphoma • Infectious Disease • Lymphoma • Marginal Zone Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Respiratory Diseases • Targeted Protein Degradation • BTK

Preliminary Efficacy and Safety of the Bruton Tyrosine Kinase Degrader BGB-16673 in Patients with Relapsed or Refractory Waldenström Macroglobulinemia: Results from the Phase 1 CaDAnCe-101 Study (ASH 2024) - P1/2 | "One patient had IgM flare at initial response assessment and went on to develop PR. Conclusions : Early data from this ongoing, first-in-human study demonstrate that the novel BTK degrader BGB-16673 has a tolerable safety profile and shows promising antitumor activity in heavily pretreated patients with BTK inhibitor–exposed R/R WM, including those with BTK and CXCR4 mutations."

Clinical • IO biomarker • P1 data • Atrial Fibrillation • Cardiovascular • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Hypertension • Infectious Disease • Lymphoma • Lymphoplasmacytic Lymphoma • Neutropenia • Oncology • Otorhinolaryngology • Respiratory Diseases • Septic Shock • Sinusitis • Targeted Protein Degradation • Waldenstrom Macroglobulinemia • BTK • CXCR4 • MYD88

Preliminary 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 Phase 1 CaDAnCe-101 Study (ASH 2024) - P1/2 | "Responses were seen at the lowest dose, as well as in patients previously treated with a cBTKi, ncBTKi, double- (cBTKi and BCL2i) and triple- (cBTKi, BCL2i, ncBTKi) exposed patients, and in patients with and without BTK mutations. Conclusions : Emerging data from this ongoing, first-in-human study demonstrate that the novel BTK degrader BGB-16673 has a tolerable safety profile and shows promising and deep overall responses in heavily pretreated patients with R/R CLL/SLL, including those with prior BTK inhibitor treatment and BTK resistance mutations."

Clinical • IO biomarker • P1 data • Atrial Fibrillation • Cardiovascular • Chronic Lymphocytic Leukemia • Fatigue • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Hypertension • Infectious Disease • Leukemia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Novel Coronavirus Disease • Oncology • Pneumonia • Respiratory Diseases • Septic Shock • Small Lymphocytic Lymphoma • Targeted Protein Degradation • BTK • IGH • TP53

BeiGene Advances Leadership in CLL at ASH 2024 with New Data From Its Hematology Franchise Including...Novel Pipeline Assets (Businesswire) - P1/2 | N=466 | CaDAnCe-101 CLL (NCT05006716) | Sponsor: BeiGene | "Data from the Phase 1/2 CaDAnCe-101 CLL study (NCT05006716) demonstrated that treatment with BGB-16673 was generally well tolerated in this heavily pretreated population of patients...From the cohort of CLL/SLL patients, BGB-16673 demonstrated an ORR of 94% at the 200mg dose. Furthermore, amongst all doses delivered, 2 patients achieved a complete remission/complete remission with incomplete count recovery (CR/CRi). Grade ≥3 TEAEs were reported in 57% of patients. The most common grade ≥3 TEAEs (≥10%) were neutropenia/neutrophil count decreased (20%) and pneumonia (10%). (Abstract 885)....From the cohort of Waldenström's macroglobulinemia patients, BGB-16673 demonstrated a 93% disease control rate (DCR) and 26% very good partial response (VGPR). Grade ≥3 TEAEs were reported in 45% of patients. The most common grade ≥3 TEAE (≥20%) was neutropenia/neutrophil count decreased. (Abstract 860)."

P1/2 data • Chronic Lymphocytic Leukemia • Hematological Malignancies • Oncology • Small Lymphocytic Lymphoma • Waldenstrom Macroglobulinemia