^
3d
New P1/2 trial
|
BCL2 (B-cell CLL/lymphoma 2)
|
Brukinsa (zanubrutinib) • sonrotoclax (BGB-11417)
4d
New P2 trial
|
Tevimbra (tislelizumab-jsgr) • Brukinsa (zanubrutinib)
13d
The efficacy of Zebutinib in first-line treatment of localized salivary gland MALT lymphoma (ChiCTR2400090558)
P4, N=33, Recruiting, Shanghai Ninth Peopole's Hospital, Shanghai Jiaotong University School of Medicine; Shanghai Ninth Peopole's Hospital, Shanghai Jiaotong University Sc
New P4 trial
|
Brukinsa (zanubrutinib)
13d
New P2 trial • Circulating tumor DNA
|
Gazyva (obinutuzumab) • Brukinsa (zanubrutinib)
17d
Acalabrutinib, Umbralisib and Ublituximab Regimen (AU2) Demonstrates High Response Rate and Undetectable Molecular Minimal Residual Disease (MRD) in Patients (pts) with De Novo Mantle Cell Lymphoma (MCL) (ASH 2024)
Two pts were switched to zanubrutinib due to PD on U2, both achieved response. AU2 is a highly effective regimen in pts with previously untreated MCL, including those with high-risk genetics (100% CR rate), and achieves a high molecular uMRD rate. Pts who develop progressive disease can be effectively salvaged with subsequent therapies.
Clinical • IO biomarker • Minimal residual disease
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TP53 (Tumor protein P53)
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TP53 mutation
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clonoSEQ
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Brukinsa (zanubrutinib) • Calquence (acalabrutinib) • Ukoniq (umbralisib) • Briumvi (ublituximab-xiiy)
17d
Multicenter Phase II Trial of Zanubrutinib, Obinutuzumab, and Venetoclax (BOVen) in Treatment-Naïve Chronic Lymphocytic Leukemia: 5-Year Follow up, Retreatment Outcomes, and Impact of MRD Kinetics (ΔMRD400) (ASH 2024)
Zanubrutinib is a second-generation BTKi with superior PFS and safety compared with ibrutinib (Brown NEJM 2023). Five-year follow up of the BOVen regimen demonstrates frequent uMRD4 in PB (96%) and BM (92%), and uMRD4 was durable with a median MRD4-free survival of 34 mo. Retreatment with zanubrutinib-venetoclax was also well-tolerated and effective. A phase 2 trial of BOVen with ΔMRD400-directed treatment duration is ongoing.
Clinical • P2 data
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clonoSEQ
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Venclexta (venetoclax) • Imbruvica (ibrutinib) • Gazyva (obinutuzumab) • Brukinsa (zanubrutinib)
17d
Combined Pirtobrutinib, Venetoclax, and Obinutuzumab As First-Line Treatment of Patients with Chronic Lymphocytic Leukemia (CLL) (ASH 2024)
Introduction: Combined treatment with covalent BTK-inhibitor (cBTKi), such as ibrutinib, acalabrutinib, or zanubrutinib with BCL2-inhibitor, venetoclax, +/- CD20 monoclonal antibody obinutuzumab showed high rates of undetectable MRD (U-MRD4, 10-4 sensitivity) remission in patients (pts) with CLL (Jain, NEJM 2019; Munir NEJM 2023; Wierda, JCO 2021; Kater, NEJM Evidence 2022). We report results of combined pirtobrutinib, venetoclax, and obinutuzumab in pts with previously untreated CLL. We observed a very high rate of BM U-MRD6 at 6-months and 12-months of combined treatment. Adverse event profile was similar to what was noted in previous studies with these agents.
Clinical • IO biomarker
|
TP53 (Tumor protein P53)
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TP53 mutation • TP53 mutation + Chr del(17p)
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clonoSEQ
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Venclexta (venetoclax) • Imbruvica (ibrutinib) • Gazyva (obinutuzumab) • Brukinsa (zanubrutinib) • Calquence (acalabrutinib) • Jaypirca (pirtobrutinib)
17d
Final Analysis of a Phase 1 Study of Zanubrutinib Plus Lenalidomide in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma (ASH 2024)
In preclinical studies, lenalidomide has been shown to induce cytotoxicity in ABC DLBCL cells by inhibiting NF-κB signaling and a synergistic effect is seen when B-cell receptor signaling is inhibited by the BTK inhibitor ibrutinib. The results of the BGB-3111-110 study demonstrated that the RP2D of zanubrutinib 160 mg twice daily plus lenalidomide 25 mg once daily had a manageable safety profile and promising efficacy in patients with R/R DLBCL. Similar efficacy was observed across DLBCL subtypes; ORR was numerically higher in the ABC subtype. Further molecular analysis is ongoing.
Clinical • P1 data • IO biomarker
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HTG EdgeSeq DLBCL Cell of Origin Assay
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Imbruvica (ibrutinib) • lenalidomide • Brukinsa (zanubrutinib)
19d
Benefit VA: A Randomized Phase II Study Of Bruton Tyrosine Kinase Inhibitor With Or Without Venetoclax In Veterans With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) (clinicaltrials.gov)
P2, N=100, Not yet recruiting, VA Office of Research and Development | Trial completion date: Dec 2029 --> Dec 2030 | Trial primary completion date: Jun 2029 --> Jun 2030
Trial completion date • Trial primary completion date
|
Venclexta (venetoclax) • Imbruvica (ibrutinib) • Brukinsa (zanubrutinib) • Calquence (acalabrutinib)
22d
New P2 trial
|
lenalidomide • Brukinsa (zanubrutinib)
24d
The efficacy and safety of ZR2 versus R-CHOP-like for elderly patients with newly diagnosed diffuse large B cell lymphoma: a single-center prospective study in China. (PubMed, Ann Hematol)
To compare the safety and efficacy of zanubrutinib plus rituximab and lenalidomide (ZR2) and R-CHOP-like for elderly patients with newly diagnosed DLBCL, we conducted this single-center prospective study. Patients with gastrointestinal DLBCL have to be monitored closely by abdominal enhanced CT every cycle. Overall, ZR2 chemo-free regimen might be more appropriate for elderly DLBCL patients.
Journal
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TP53 (Tumor protein P53) • CARD11 (Caspase Recruitment Domain Family Member 11)
|
TP53 mutation • CARD11 mutation
|
Rituxan (rituximab) • lenalidomide • Brukinsa (zanubrutinib)
24d
G-Pola-ZLP in Diffuse Large B-Cell Lymphoma (clinicaltrials.gov)
P2, N=80, Not yet recruiting, Navy General Hospital, Beijing
New P2 trial
|
lenalidomide • Brukinsa (zanubrutinib) • prednisone • Polivy (polatuzumab vedotin-piiq) • Columvi (glofitamab-gxbm)
25d
Pola-ZR2P in Previously Untreated DLBCL (clinicaltrials.gov)
P2, N=80, Not yet recruiting, Navy General Hospital, Beijing
New P2 trial
|
Rituxan (rituximab) • lenalidomide • Brukinsa (zanubrutinib) • prednisone • Polivy (polatuzumab vedotin-piiq)
26d
Phase classification • Combination therapy
|
Gazyva (obinutuzumab) • Brukinsa (zanubrutinib)
27d
Advances in Targeted Therapy: Addressing Resistance to BTK Inhibition in B-Cell Lymphoid Malignancies. (PubMed, Cancers (Basel))
The first-in-class covalent BTK inhibitor, Ibrutinib, binds to the C481 amino acid residue to block the BTK enzyme and prevent the downstream signaling...To bypass the C481S mutation, non-covalent BTKi, such as Pirtobrutinib, were developed and are active against both wild-type and the C481S mutation...In addition, we discuss the new emerging class of BTK degraders, which utilize the evolution of proteolysis-targeting chimeras (PROTACs) to degrade the BTK protein and constitute an important avenue of overcoming resistance. The moving landscape of resistance to BTKi and the development of new therapeutic strategies highlight the ongoing advances being made towards the pursuit of a cure for B-cell lymphoid malignancies.
Review • Journal
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PLCG2 (Phospholipase C Gamma 2)
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BTK C481S • BTK C481
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Imbruvica (ibrutinib) • Brukinsa (zanubrutinib) • Calquence (acalabrutinib) • Jaypirca (pirtobrutinib)
1m
Enrollment open • Combination therapy
|
Gazyva (obinutuzumab) • Brukinsa (zanubrutinib)
1m
R-ICE+X: Novel Targeted Drugs Combined With R-ICE Regimen in Relapsed and Refractory Diffuse Large B-cell Lymphoma (clinicaltrials.gov)
P2, N=76, Recruiting, Ruijin Hospital | Trial primary completion date: Jun 2024 --> Jun 2025
Trial primary completion date
|
carboplatin • Brukinsa (zanubrutinib) • decitabine • Epidaza (chidamide) • pomalidomide • tofacitinib
1m
Zanubrutinib, Obinutuzumab, and Venetoclax for First-Line Treatment of Mantle Cell Lymphoma with a TP53 Mutation. (PubMed, Blood)
These data support its use and further evaluation of the BOVen regimen in this high-risk population. NCT03824483.
Journal • IO biomarker
|
TP53 (Tumor protein P53)
|
TP53 mutation
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Venclexta (venetoclax) • Gazyva (obinutuzumab) • Brukinsa (zanubrutinib)
1m
New P4 trial
|
Venclexta (venetoclax) • Rituxan (rituximab) • Gazyva (obinutuzumab) • Brukinsa (zanubrutinib) • Calquence (acalabrutinib)
1m
New P2 trial
|
cytarabine • Brukinsa (zanubrutinib) • etoposide IV • carmustine • melphalan
1m
New P2 trial
|
Rituxan (rituximab) • Brukinsa (zanubrutinib)
1m
CHESS: Zanubrutinib and Rituximab Followed by R-DHAOx Then Maintenance with Zanubrutinib for Newly-Diagnosed MCL (clinicaltrials.gov)
P2, N=42, Active, not recruiting, Sun Yat-sen University | Recruiting --> Active, not recruiting | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2024
Enrollment closed • Trial completion date • Trial primary completion date
|
TP53 (Tumor protein P53) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CD20 (Membrane Spanning 4-Domains A1)
|
TP53 mutation • CD20 positive
|
Rituxan (rituximab) • cytarabine • oxaliplatin • Brukinsa (zanubrutinib) • dexamethasone injection
1m
New P2 trial
|
Brukinsa (zanubrutinib) • thiotepa • methotrexate IV
1m
New P2 trial
|
Brukinsa (zanubrutinib)
1m
Enrollment closed • CAR T-Cell Therapy
|
BCL2 (B-cell CLL/lymphoma 2) • BCL6 (B-cell CLL/lymphoma 6) • IRF4 (Interferon regulatory factor 4)
|
BCL6 rearrangement • BCL2 rearrangement
|
Brukinsa (zanubrutinib)
1m
GLOASIS: A Phase II Study Evaluating Glofitamab in Combination With Venetoclax Plus Zanubrutinib or Venetoclax Alone in Subjects With Untreated or Relapsed/Refractory High-risk Mantle-cell Lymphoma (clinicaltrials.gov)
P2, N=100, Not yet recruiting, The Lymphoma Academic Research Organisation | Trial completion date: Dec 2031 --> Mar 2032 | Initiation date: Sep 2024 --> Dec 2024 | Trial primary completion date: Feb 2028 --> May 2028
Trial completion date • Trial initiation date • Trial primary completion date • Combination therapy
|
Venclexta (venetoclax) • Gazyva (obinutuzumab) • Brukinsa (zanubrutinib) • Columvi (glofitamab-gxbm)
1m
New P2 trial
|
BCL2 (B-cell CLL/lymphoma 2)
|
Brukinsa (zanubrutinib) • sonrotoclax (BGB-11417)
1m
Comparative safety of novel targeted therapies in relapsed/refractory chronic lymphocytic leukemia: a network meta-analysis. (PubMed, Ther Adv Med Oncol)
However, bendamustine + rituximab had a more favorable safety profile for grade ⩾3 AEs when compared with ibrutinib (risk ratio 0.62 (95% credible interval 0.40-0.86)), acalabrutinib (0.69 (0.45-0.94)), zanubrutinib (0.64 (0.42-0.91)), and venetoclax + rituximab (0.87 (0.79-0.96)). Our findings showed that venetoclax + rituximab, acalabrutinib, and zanubrutinib have acceptable safety profiles, which indicates that they may be the preferred therapeutic options in the setting of relapsed/refractory CLL. PROSPERO CRD42022304330.
Clinical • Retrospective data • Journal
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BCL2 (B-cell CLL/lymphoma 2)
|
Venclexta (venetoclax) • Imbruvica (ibrutinib) • Rituxan (rituximab) • Brukinsa (zanubrutinib) • Calquence (acalabrutinib) • bendamustine
1m
New P1/2 trial
|
Brukinsa (zanubrutinib) • sonrotoclax (BGB-11417) • BGB-16673
2ms
BGB-3111-111: Study of Zanubrutinib in Japanese Participants With B-Cell Malignancies (clinicaltrials.gov)
P1/2, N=55, Active, not recruiting, BeiGene | Trial completion date: Sep 2024 --> Jun 2025
Trial completion date
|
Brukinsa (zanubrutinib)
2ms
ARIADNE: Zanubrutinib in Patients With Waldenström's Macroglobulinemia, Chronic Lymphocytic Leukemia, Marginal Zone Lymphoma and Follicular Lymphoma (clinicaltrials.gov)
P=N/A, N=605, Recruiting, iOMEDICO AG | N=400 --> 605 | Trial completion date: Apr 2027 --> Aug 2028 | Trial primary completion date: Apr 2027 --> Aug 2028
Enrollment change • Trial completion date • Trial primary completion date
|
Gazyva (obinutuzumab) • Brukinsa (zanubrutinib)
2ms
Sustained Benefit of Zanubrutinib vs Ibrutinib in Patients With R/R CLL/SLL: Final Comparative Analysis of ALPINE. (PubMed, Blood)
Incidence of atrial fibrillation/flutter was lower with zanubrutinib vs ibrutinib (7.1% vs 17.0%); no cardiac deaths were reported with zanubrutinib vs six cardiac deaths with ibrutinib. This analysis, at 42.5 months median follow-up, demonstrates that zanubrutinib remains more efficacious than ibrutinib with an improved overall safety/tolerability profile.
Journal
|
TP53 (Tumor protein P53)
|
TP53 mutation • TP53 mutation + Chr del(17p)
|
Imbruvica (ibrutinib) • Brukinsa (zanubrutinib)
2ms
HOVON169CAD: Zanubrutinib in Primary Cold Agglutinin Disease (clinicaltrials.gov)
P2, N=25, Recruiting, Stichting Hemato-Oncologie voor Volwassenen Nederland | Not yet recruiting --> Recruiting
Enrollment open
|
CD20 (Membrane Spanning 4-Domains A1)
|
CD20 positive
|
Brukinsa (zanubrutinib)
2ms
New trial
|
Rituxan (rituximab) • Brukinsa (zanubrutinib) • etoposide IV • leucovorin calcium
2ms
New P2 trial
|
Rituxan (rituximab) • doxorubicin hydrochloride • cyclophosphamide • Brukinsa (zanubrutinib)
2ms
BGB-3111-217: Zanubrutinib in Participants With Active Proliferative Lupus Nephritis (clinicaltrials.gov)
P2, N=177, Completed, BeiGene | Active, not recruiting --> Completed
Trial completion
|
Brukinsa (zanubrutinib)
2ms
Trial completion • Combination therapy
|
MSI (Microsatellite instability)
|
MSI-H/dMMR
|
paclitaxel • Tevimbra (tislelizumab-jsgr) • Brukinsa (zanubrutinib) • BGB-10188
2ms
Zanubrutinib and Lenalidomide as Maintenance Therapy in DLBCL (clinicaltrials.gov)
P2, N=240, Recruiting, Navy General Hospital, Beijing | Not yet recruiting --> Recruiting
Enrollment open
|
lenalidomide • Brukinsa (zanubrutinib)
2ms
CELESTIAL-TNCLL: AN ONGOING, OPEN-LABEL, MULTIREGIONAL, PHASE 3 STUDY OF SONROTOCLAX (BGB-11417) + ZANUBRUTINIB VS VENETOCLAX + OBINUTUZUMAB IN TREATMENT-NAIVE CLL (SIE 2024)
The combination of venetoclax (ven), the first-generation BCL2 inhibitor, and ibrutinib, a BTK inhibitor, has efficacy in CLL. Other secondary endpoints include investigator (INV)-assessed PFS, CRR-INV, uMRD4 rate by flow cytometry, ORR-IRC and -INV, DOR-IRC and -INV, patient-reported outcomes, and safety and tolerability. Recruitment is ongoing.
Clinical • P3 data • IO biomarker
|
TP53 (Tumor protein P53)
|
TP53 mutation • TP53 mutation + Chr del(17p)
|
clonoSEQ
|
Venclexta (venetoclax) • Imbruvica (ibrutinib) • Gazyva (obinutuzumab) • Brukinsa (zanubrutinib) • sonrotoclax (BGB-11417)
2ms
A highly selective PI3Kδ inhibitor BGB-10188 shows superior preclinical anti-tumor activities and decreased on-target side effects on colon. (PubMed, Neoplasia)
BGB-10188 showed significant antitumor effects in human B cell lymphoma xenograft models as single agent or in combination with the BTK inhibitor zanubrutinib. BGB-10188 showed significant Treg inhibition in blood but not in colon, along with less drug accumulation in colon compared with idelalisib, which is an approved PI3Kdelta inhibitor with high incidence of gastrointestinal side effects in clinic. In summary, BGB-10188 is a novel PI3Kδ inhibitor with high selectivity, potency and improved safety profile shown in preclinical studies, which is showing the potential as a best-in-class PI3Kδ inhibitor.
Preclinical • Journal • Adverse events
|
PIK3CD (Phosphatidylinositol-4 5-Bisphosphate 3-Kinase Catalytic Subunit Delta)
|
Brukinsa (zanubrutinib) • Zydelig (idelalisib) • BGB-10188
3ms
Zanubrutinib, Lenalidomide and Rituximab (ZR2) in Elderly Treatment-naive Patients with Diffuse Large B-cell Lymphoma (DLBCL) (clinicaltrials.gov)
P2, N=40, Active, not recruiting, Ruijin Hospital | Trial completion date: Aug 2023 --> Dec 2024
Trial completion date
|
Rituxan (rituximab) • lenalidomide • Brukinsa (zanubrutinib)
3ms
ZBR: Zanubrutinib Plus BR in Newly Diagnosed Symptomatic WM (clinicaltrials.gov)
P2, N=42, Recruiting, Institute of Hematology & Blood Diseases Hospital, China | N=30 --> 42
Enrollment change
|
Rituxan (rituximab) • Brukinsa (zanubrutinib) • bendamustine