Zykadia (ceritinib) / Novartis 
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 20 Diseases   18 Trials   18 Trials   1690 News 


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  • ||||||||||  Review, Journal:  Therapeutic strategies in advanced ALK positive non-small cell lung cancer (Pubmed Central) -  Jun 28, 2020   
    The emergence of crizotinib drug resistance has prompted the development of next generation drugs including ceritinb, alectinib, brigatinib and lorlatinib. The ability to quickly develop targeted therapies against specific oncogenic drivers will require close co-operation between pathologists, pulmonologists and oncologists in the future to keep pace with drug discoveries and to define optimal therapeutic strategies.
  • ||||||||||  Journal:  Drug discovery targeting anaplastic lymphoma kinase (ALK). (Pubmed Central) -  Jun 26, 2020   
    This review provides an overview of the physiological and biological functions of ALK, the discovery and development of ALK drugs by focusing on their chemotypes, inhibitory activity, selectivity and resistance, as well as current status. Additionally, the mechanism of drug resistance and potential therapeutic strategies to overcome drug resistance are also summarized.
  • ||||||||||  Zykadia (ceritinib) / Novartis
    Preclinical, Journal, PD(L)-1 Biomarker, IO Biomarker:  In vitro and in vivo synergistic efficacy of ceritinib combined with PD-L1 inhibitor in ALK-rearranged NSCLC. (Pubmed Central) -  Jun 25, 2020   
    CER could synergize with PD-1/PD-L1 blockade to yield enhanced anti-tumor responses along with favorable tolerability of adverse effects. CER and PD-L1 inhibitor combined produced a synergistic antineoplastic efficacy in vitro and in vivo, which provide a key insight and proof of principle for evaluating CER plus PD-L1 blockade as combination therapy in clinical therapeutic practice.
  • ||||||||||  Trial initiation date, Adverse events, Checkpoint inhibition:  PD-1 Immune Checkpoint Inhibitors and Immune-Related Adverse Events: a Cohort Study (clinicaltrials.gov) -  May 27, 2020   
    P=N/A,  N=4724, Not yet recruiting, 
    Our results indicate that compared with crizotinib and alectinib, ceritinib is a cost-effective option for treatment-naïve patients with ALK-positive advanced NSCLC. Initiation date: Apr 2020 --> Jul 2020
  • ||||||||||  Zykadia (ceritinib) / Novartis, Vitrakvi (larotrectinib) / Bayer, Eli Lilly, Faslodex (fulvestrant) / AstraZeneca
    Kinase fusions drive endocrine resistance in estrogen receptor-positive breast cancer (Virtual Meeting II: E-Posters) -  May 16, 2020 - Abstract #AACRII2020AACR-II_3907;    
    Similarly, expression of the EML4-ALK fusion also activated growth factor signaling pathways and caused resistance to estrogen depletion and induced sensitivity to the ALK inhibitor, Ceritinib...Two patients with acquired LMNA-NTRK1 fusions and metastatic disease received larotrectinib and demonstrated clinical benefit. Overall, our findings demonstrate that kinase fusions promote endocrine resistance in ER-positive breast cancer, and suggest that fusion screening in advanced breast cancer, particularly those with ER-positive breast cancer at progression on hormone therapy can identify rare tumors harboring targetable kinase fusions.
  • ||||||||||  TPX-0131 / Turning Point Therapeutics
    TPX-0131: A next generation macrocyclic ALK inhibitor that overcomes ALK resistant mutations refractory to current approved ALK inhibitors (Virtual Meeting II: E-Posters) -  May 16, 2020 - Abstract #AACRII2020AACR-II_3327;    
    Second generation ALK inhibitors alectinib, ceritinib, and brigatinib were able to overcome the majority of ALK resistant mutations (L1196M, G1269A and F1174L) acquired with crizotinib...Lorlatinib, a third generation ALK inhibitor, can overcome G1202R resistance with moderate IC50 values of 40 - 60 nM in cell-based assays...Taken together, TPX-0131 is a next generation ALK inhibitor that can overcome a broad spectrum of acquired resistance mutations, especially the G1202R solvent front mutation and compound mutations (e.g. L1196M/G1202R). The nonclinical pharmacology profile of TPX-0131 warrants further preclinical investigation.
  • ||||||||||  Zykadia (ceritinib) / Novartis, Mekinist (trametinib) / Novartis
    Frontline therapy with anti-PD1 enhances the durability of combination targeted therapy in NRAS-mutant melanoma (Virtual Meeting II: E-Posters) -  May 16, 2020 - Abstract #AACRII2020AACR-II_247;    
    Successive treatment with combination targeted therapy not only increases antigen presentation to T cells but also decreases recruitment of immunosuppressive MDSCs thus preventing immune escape and tumor progression. In summary, we have developed novel targeted therapy combinations that can be sequentially used with immunotherapy to maximize the durations of response in treatment of NRAS-mutant melanoma.
  • ||||||||||  Afinitor (everolimus) / Novartis
    Organoid based functional test to predict personalized treatment in cholangiocarcinoma (Virtual Meeting II: E-Posters) -  May 16, 2020 - Abstract #AACRII2020AACR-II_2192;    
    While these results correlate well with genomically predicted drug sensitivities, all patients showed additional drug sensitivities beyond those predicted by genomics offering patients additional potential treatment options. This study highlights the importance of functional data in a genetically heterogenous tumor type such as CCA.
  • ||||||||||  Zykadia (ceritinib) / Novartis
    Enrollment closed, Enrollment change, Trial completion date:  Preoperative Ceritinib (LDK378) in Glioblastoma Multiforme and CNS Metastasis (clinicaltrials.gov) -  May 14, 2020   
    P1,  N=10, Active, not recruiting, 
    Sequential use of ALK kinase inhibitors can be an efficient strategy to counter drug resistance. Recruiting --> Active, not recruiting | N=48 --> 10 | Trial completion date: Sep 2017 --> Sep 2020
  • ||||||||||  Zykadia (ceritinib) / Novartis
    Journal, Pleural Effusion:  Diffuse infiltrative lung disease, pericarditis, pleural effusion and ceritinib hypersensitivity (Pubmed Central) -  May 1, 2020   
    Pleural effusion, pericarditis and diffuse pulmonary infiltration associated to ceritinib have not often been described previously. Despite few data of pulmonary toxicity related to ceritinib, the current observation highlights the need for caution and regular monitoring when using these inhibitors.
  • ||||||||||  Xalkori (crizotinib) / Pfizer, Zykadia (ceritinib) / Novartis
    Journal:  ALK Inhibitors-Induced M Phase Delay Contributes to the Suppression of Cell Proliferation. (Pubmed Central) -  Apr 30, 2020   
    H2228 human lung carcinoma cells that express EML4-ALK fusion showed M phase delay in the presence of TAE684 at about IC concentrations. These results suggest that ALK plays a role in M phase regulation and ALK inhibition may contribute to the suppression of cell proliferation in ALK-expressing cancer cells.
  • ||||||||||  [VIRTUAL] Trends in ALK inhibitors for non-small cell lung cancer. () -  Apr 29, 2020 - Abstract #ASCO2020ASCO_3210;    
    Furthermore, the increased ER and in-patient costs may substantiate the findings of the ALEX trial, notably higher liver toxicity and more nausea, vomiting, and diarrhea for crizotinib. There is not yet sufficient data on the newer ALK inhibitors, brigatinib and lorlatinib in the real-world.
  • ||||||||||  Zykadia (ceritinib) / Novartis
    Preclinical, Journal, Myeloid-derived suppressor cells:  LDK378 inhibits the recruitment of myeloid derived suppressor cells to spleen via the p38/GRK2/CCR2 pathway in mice with sepsis. (Pubmed Central) -  Apr 26, 2020   
    Furthermore, in vitro experiments also showed that lipopolysaccharide (LPS)-induced migration of MDSCs was similarly owing to the activation of GRK2 and up-regulation of CCR2 by LPS, whereas the treatment with LDK378 partially blocked the LPS-induced phosphorylation of p38 and GRK2 and decreased the expression of CCR2 on the cell surface, therefore leading to the suppression of MDSC migration. Together, these findings unravel a novel function of LDK378 in the host response to infection and suggest that LDK378 could be a potential therapeutic agent for sepsis.
  • ||||||||||  Cabometyx (cabozantinib tablet) / Takeda, Exelixis, Ipsen
    Retrospective data, Journal:  Comparative Efficacy of Targeted Therapies in Patients with Non-Small Cell Lung Cancer: A Network Meta-Analysis of Clinical Trials. (Pubmed Central) -  Apr 15, 2020   
    Compared with chemotherapy, both ORR and PFS were significantly improved for afatinib, alectinib, and crizotinib, while only PFS was significantly improved for cabozantinib, ceritinib, gefitinib, and osimertinib...Cabozantinib and alectinib showed the highest probability for the first-line treatment ranking in ORR (62.5%) and PFS (87.5%), respectively. The current network meta-analysis showed the comprehensive evidence-based comparative efficacy of different types of targeted therapies, which would help clinicians use targeted therapies in clinical practice.
  • ||||||||||  Zykadia (ceritinib) / Novartis, Mekinist (trametinib) / Novartis, BeiGene
    Phase classification:  Study of Trametinib + Ceritinib in Patients With Unresectable Melanoma (clinicaltrials.gov) -  Apr 8, 2020   
    P1,  N=27, Suspended, 
    The patients from Japanese cohorts had a higher incidence of ALK-inhibitor pneumonitis, which indicates the need for increased awareness and caution for pneumonitis in Japanese patients treated with ALK inhibitors. Phase classification: P2 --> P1
  • ||||||||||  Zykadia (ceritinib) / Novartis, Cabometyx (cabozantinib tablet) / Takeda, Exelixis, Ipsen, Sprycel (dasatinib) / BMS, Otsuka, Inhibikase
    Clinical, Journal:  Safety and Activity of the Combination of Ceritinib and Dasatinib in Osteosarcoma. (Pubmed Central) -  Apr 1, 2020   
    The ceritinib/dasatinib combination was applied to the primary cells of a 16-year-old girl with a long history of lung metastases, and was more effective than cabozantinib and olaparib...After the cessation of the therapy, radiological analysis indicated a massive growth of the patient's liver metastases. In conclusion, these data indicate that the combination of ceritinib/dasatinib is safe and may be used to develop new therapy protocols.
  • ||||||||||  Zykadia (ceritinib) / Novartis
    Clinical, Journal, Combination therapy:  Interpretation of ceritinib clinical trial results and future combination therapy strategies for ALK-rearranged NSCLC. (Pubmed Central) -  Mar 22, 2020   
    The ALK gene is rearranged in 3-7% of NSCLCs, and targeted inhibition of ALK is a viable therapy option.Areas covered: We discuss the available treatment options for ALK-positive NSCLC with an emphasis on the second-generation ALK inhibitor ceritinib. We also discuss practical treatment strategies and possible strategies to overcome or delay resistance to ALK inhibitors.Expert opinion: With a robust treatment armamentarium for patients with ALK-positive NSCLC, emphasis has shifted to optimizing individualized treatment strategies to further enhance outcomes for these patients.
  • ||||||||||  Zykadia (ceritinib) / Novartis, pictilisib (GDC-0941) / Roche
    Journal:  Codrug Approach for the Potential Treatment of EML4-ALK Positive Lung Cancer. (Pubmed Central) -  Mar 19, 2020   
    We have joined the two drugs through a new, pH-sensitive linker where the resulting codrugs are hydrolytically stable at lower pH (pH 6.4) but rapidly cleaved at higher pH (pH 7.4). Compound (19), which was designed for optimal lung retention, demonstrated clean liberation of the drug payloads in vitro and represents a novel approach to targeted lung delivery.