- |||||||||| Brukinsa (zanubrutinib) / BeiGene
Enrollment open, Trial initiation date: Zanubrutinib in the Treatment of Relapsed/Refractory wAIHA (clinicaltrials.gov) - Apr 25, 2024
P2, N=22, Recruiting,
Overall, the addition of zanubrutinib to selinexor monotreatment had a synergistic effect in Not yet recruiting --> Recruiting | Initiation date: Jun 2023 --> Nov 2023
- |||||||||| Brukinsa (zanubrutinib) / BeiGene
Trial completion, Enrollment change, Trial completion date, Trial primary completion date, Monotherapy: Zanubrutinib for HLH (clinicaltrials.gov) - Apr 11, 2024
P3, N=16, Completed,
Enrolling by invitation --> Recruiting Recruiting --> Completed | N=30 --> 16 | Trial completion date: Apr 2023 --> Aug 2023 | Trial primary completion date: Jan 2023 --> Aug 2023
- |||||||||| Brukinsa (zanubrutinib) / BeiGene, Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku, Calquence (acalabrutinib) / AstraZeneca
Journal: An indirect comparison of acalabrutinib with and without obinutuzumab versus zanubrutinib in treatment-naive CLL. (Pubmed Central) - Apr 10, 2024
No other significant differences in safety were observed. In summary, compared with zanubrutinib, acalabrutinib plus obinutuzumab had longer INV-PFS with increased odds of neutropenia and arthralgia, whereas acalabrutinib monotherapy had similar INV-PFS with lower odds of any grade hypertension.
- |||||||||| dasatinib / Generic mfg.
Journal, Combination therapy: Development of combination therapies with BTK inhibitors and dasatinib to treat CNS-infiltrating E2A-PBX1+/preBCR+ ALL. (Pubmed Central) - Apr 10, 2024
Hence, dasatinib with ibrutinib reduced pPLCG2 and pBTK in primary ALL patient samples, including E2A-PBX1+ ALLs. In summary, genetic depletion and pharmacological inhibition of BTK increase dasatinib effects in human and mouse E2A-PBX1+/preBCR+ ALL in most of performed assays, and the combination of dasatinib and BTKi is very effective in reducing CNS-infiltration of E2A-PBX1+/preBCR+ ALL cells in vivo.
- |||||||||| Journal: New means and challenges in the targeting of BTK. (Pubmed Central) - Apr 5, 2024
Newer noncovalent BTK inhibitors, such as pirtobrutinib, overcome C481 mutation-mediated resistance but are susceptible to other kinase domain mutations, particularly at residues Threonine 474 and Leucine 528...Importantly, newer generation covalent BTK inhibitors zanubrutinib and acalabrutinib are susceptible to the same mutations which confer resistance to non-covalent inhibitors...This observation suggests that BTK may act independently of its kinase activity as a scaffold. Thus, the timely development of BTK degrading proteolysis targeting drugs has allowed for degradation, rather than just enzymatic inhibition, of BTK in B-cell lymphomas and early clinical trials to evaluate BTK degraders are underway.
- |||||||||| Brukinsa (zanubrutinib) / BeiGene, Calquence (acalabrutinib) / AstraZeneca, Imbruvica (ibrutinib) / AbbVie, J&J
Journal, Adverse events: Investigating bleeding adverse events associated with BTK inhibitors in the Food and Drug Administration adverse event reporting system (FAERS). (Pubmed Central) - Apr 3, 2024
The incidence of bleeding AEs was higher with ibrutinib (Case number?=?10,696) than with zanubrutinib (Case number?=?213) and acalabrutinib (Case number?=?314). Our findings indicate that bleeding AEs linked to BTK inhibitors in various conditions underscore the need for cautious clinical decision-making, particularly in nervous system disorders, injuries, poisoning, surgical complications, vascular disorders, and others.
- |||||||||| Brukinsa (zanubrutinib) / BeiGene
Trial completion: BGB-3111-110: Zanubrutinib, in Combination With Lenalidomide, With or Without Rituximab in Participants With Relapsed/Refractory Diffuse Large B-Cell Lymphoma (clinicaltrials.gov) - Apr 3, 2024
P1, N=66, Completed,
Our findings indicate that bleeding AEs linked to BTK inhibitors in various conditions underscore the need for cautious clinical decision-making, particularly in nervous system disorders, injuries, poisoning, surgical complications, vascular disorders, and others. Recruiting --> Completed
- |||||||||| Review, Journal: Targeting BTK in B Cell Malignancies: From Mode of Action to Resistance Mechanisms. (Pubmed Central) - Apr 1, 2024
Non-covalent BTKi, such as pirtobrutinib, have been developed and proven effective in patients carrying both Cys-481-mutated and unmutated BTK. Moreover, targeting BTK with proteolysis-targeting chimeras (PROTACs) represents a promising strategy to overcome resistance to BTKi in B cell neoplasms.
- |||||||||| Brukinsa (zanubrutinib) / BeiGene, Rituxan (rituximab) / Roche
Enrollment open, Trial completion date, Trial primary completion date, Combination therapy: Zanubrutinib in Combination With R-CHOP (ZaR-CHOP) for Newly Diagnosed Diffuse Large B-Cell Lymphoma (clinicaltrials.gov) - Mar 21, 2024
P1, N=24, Recruiting,
Combination chemotherapy-free fixed-duration regimens with targeted molecules will allow for MRD-driven approach in patients with CLL/SLL in the near future. Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024 | Suspended --> Recruiting
- |||||||||| Brukinsa (zanubrutinib) / BeiGene, Calquence (acalabrutinib) / AstraZeneca, Imbruvica (ibrutinib) / AbbVie, J&J
Journal: Molecular Insights into the Impact of Mutations on the Binding Affinity of Targeted Covalent Inhibitors of BTK. (Pubmed Central) - Mar 19, 2024
The TCIs studied include ibrutinib, acalabrutinib, and zanubrutinib?all of which are FDA-approved drugs for treating multiple forms of leukemia and lymphoma. Our results offer useful molecular insights into the structural determinants, thermodynamics, and conformational energies that impact ligand binding for this biological target of clinical relevance.
- |||||||||| Brukinsa (zanubrutinib) / BeiGene
Journal: Cardiovascular events reported in patients with B-cell malignancies treated with zanubrutinib. (Pubmed Central) - Mar 19, 2024
P1, P1/2,
These data support zanubrutinib as a treatment option with improved cardiovascular tolerability over ibrutinib for patients with B-cell malignancies in need of BTK inhibitors. CT# NCT03053440 NCT03336333 NCT03734016 NCT04170283 NCT03206918 NCT03206970 NCT03332173 NCT03846427 NCT02343120 NCT03189524.
- |||||||||| Tevimbra (tislelizumab) / BeiGene, Brukinsa (zanubrutinib) / BeiGene
Trial initiation date, CAR T-Cell Therapy: ZeTA: A Study to Evaluate Zanubrutinib and Tislelizumab in Progressive Lymphoma Post CAR-T (clinicaltrials.gov) - Mar 12, 2024
P2, N=76, Not yet recruiting,
This study suggests that newly diagnosed DLBCL patients with MYD88mut and/or CD79Bmut may benefit from BTKis according to real-world clinical data. Initiation date: Jan 2024 --> Aug 2024
- |||||||||| Patient Characteristics and Treatment Patterns in Patients with Chronic Lymphocytic Leukemia in China: A Real-World, Contemporary Cohort Study () - Mar 8, 2024 - Abstract #ISPOR2024ISPOR_473;
Among those receiving targeted therapy, 335 (74.4%), 98 (21.8%), 5 (1.1%), 4 (0.9%), and 8 (1.8%) used ibrutinib, zanubrutinib, orelabrutinib, venetoclax, and lenalidomide. In this real-world study using regional healthcare data, distinct demographic, clinical, and tumor-related characteristics were observed, providing a comprehensive overview of CLL management in China.
- |||||||||| Brukinsa (zanubrutinib) / BeiGene, Rituxan (rituximab) / Roche, Imbruvica (ibrutinib) / AbbVie, J&J
Clinical Consequences and Associated Costs of Treating Patients With Waldenstr () - Mar 8, 2024 - Abstract #ISPOR2024ISPOR_457;
A semi-Markov simulation model was constructed to estimate the clinical outcomes and cost of 1L treatment with ibrutinib, zanubrutinib, and rituximab-based regimens, including bendamustine+rituximab (BR) for patients with WM in the 1L setting from a US Medicare perspective. Using base case assumptions and conservative estimates of clinical effectiveness from package inserts and pivotal trial publications, modeled clinical outputs suggest similar clinical benefits across WM treatments in 1L settings.
- |||||||||| methotrexate / Generic mfg.
Cough-headache as a Novel Presentation of Methotrexate Neurotoxicity (Colorado Convention Center | Exhibit Hall B-E) - Mar 8, 2024 - Abstract #AAN2024AAN_3488;
Patients receiving high-dose or intrathecal MTX are also at high risk of spontaneous intracerebral hemorrhage which should first be ruled out. Following initial imaging, MTX neurotoxicity should be considered in the differential with appropriate imaging ordered to evaluate for its presence.
- |||||||||| Safety of CAR T-Cell Therapy in Patients with Active Autoimmune Diseases: A Case Report (Colorado Convention Center | Exhibit Hall B-E) - Mar 8, 2024 - Abstract #AAN2024AAN_2606;
Ultimately, she proceeded with lisocabtagene maraleucel (liso-cel) CAR-T. She had CRS grade 1 (fever) treated with tocilizumab and dexamethasone...We hope that our experience might open the discussion for broader use of CAR-T in oncology patients with autoimmune and paraneoplastic syndromes.
- |||||||||| detorsertib (GT0486) / Kintor Pharma
GT0486, a novel mTORC1/2 dual inhibitor, exhibits synergistic antitumor efficacy in combination with BTK inhibitors (Section 46) - Mar 5, 2024 - Abstract #AACR2024AACR_7826;
Compared with other mTOR inhibitors (GDC-0349, AZD-2014, Rapamycin, GDC-0941, and CC-223), GT0486 exhibits the stronger inhibitory activity on human tumor cells, such as U87(glioma), PC-3(prostate cancer), MDA-MB-468(breast cancer) and Huh-7(liver cancer)...High synergistic effects were observed with GT0486 in combination with BTK inhibitors, including Acalabrutinib, Ibrutinib, Zanubrutinib and Orelabrutinib in the BTKi sensitive TMD8 cells...These results demonstrate that GT0486 is a promising dual mTOR1/2 inhibitor, which is currently undergoing clinical phase I study in China for the treatment of solid tumors. Strong synergistic effects observed with GT0486 in combination with BTKi in this study might open a way for a novel treatment strategy in clinical trials.
- |||||||||| Review, Journal: Bruton's Tyrosine Kinase Inhibitors: Recent Updates. (Pubmed Central) - Feb 28, 2024
Similarly, the BTK receptor is involved in signaling pathways such as chemokine receptor signaling, Toll-like receptor signaling, and Fc receptor signaling. Due to their unique mechanism, these agents provide a diverse utility in a variety of disease states not limited to the field of malignant hematology and are generally well-tolerated.
- |||||||||| Review, Journal: Frontline Therapy of CLL-Changing Treatment Paradigms. (Pubmed Central) - Feb 27, 2024
Additionally, venetoclax-based approaches, combined with anti-CD20 antibodies, have allowed for time-limited targeted therapeutic strategies which are particularly attractive for certain subsets of patients though have demonstrated efficacy across all subgroups...CLL patients requiring frontline therapy have a unique burden of choice between highly effective therapies that differ substantially with respect to side effect profiles and schedules. This review will focus on the frontline management of CLL in the setting of these rapidly changing options.
- |||||||||| Brukinsa (zanubrutinib) / BeiGene
Clinical, Review, Journal: Identifying and addressing unmet clinical needs on the use of (Pubmed Central) - Feb 20, 2024
Based on a critical discussion of data, the panel produced recommendations for using zanubrutinib and proposals for new studies to increase the evidence for the optimal treatment of patients with CLL. The recommendations given by the panel are intended for use not only by expert centers but, above all, by less experienced hematologists as well as general practitioners.
- |||||||||| Brukinsa (zanubrutinib) / BeiGene
Trial primary completion date: BGB-3111-111: Study of Zanubrutinib in Japanese Participants With B-Cell Malignancies (clinicaltrials.gov) - Feb 15, 2024
P1/2, N=55, Active, not recruiting,
The recommendations given by the panel are intended for use not only by expert centers but, above all, by less experienced hematologists as well as general practitioners. Trial primary completion date: Sep 2024 --> May 2023
- |||||||||| Brukinsa (zanubrutinib) / BeiGene, Imbruvica (ibrutinib) / AbbVie, J&J
Biomarker, Journal: Biomarker analysis of the ASPEN study comparing zanubrutinib to ibrutinib in patients with Waldenstr (Pubmed Central) - Feb 5, 2024
P3
In TP53MUT, compared to ibrutinib, zanubrutinib-treated patients had higher VGPR+CR (34.6% vs 13.6%, P<0.05), numerically improved MRR (80.8% vs 63.6%, P=0.11), and longer PFS (not reached vs 44.2 months, HR=0.66, P=0.37). Collectively, WM patients with CXCR4MUT or TP53MUT had worse prognosis compared to patients with WT alleles and zanubrutinib led to better clinical outcomes.
- |||||||||| FDA event, Journal: An Expedition on Synthetic Methodology of FDA-approved Anticancer Drugs (2018-2021). (Pubmed Central) - Jan 30, 2024
The review comprises the key structural features, approval times, target selectivity, mechanisms of action, therapeutic indication, formulations, and possible synthetic approaches of these approved drugs. These crucial details will benefit the scientific community for futuristic new developments in this arena.
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