Zykadia (ceritinib) / Novartis 
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 20 Diseases   19 Trials   19 Trials   1670 News 


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  • ||||||||||  Zykadia (ceritinib) / Novartis
    Phase 0 trial of ceritinib in brain metastases and recurrent glioblastoma (Poster Area (Hall 4)) -  Sep 11, 2019 - Abstract #ESMO2019ESMO_1557;    
    P0
    Unbound drug concentrations achieved in brain metastasis and glioblastoma are unlikely sufficient for target modulation. Clinical trial identification: NCT02605746.
  • ||||||||||  Cabometyx (cabozantinib tablet) / Takeda, Exelixis, Ipsen
    Journal:  Enhancing the Oral Absorption of Kinase Inhibitors Using Lipophilic Salts and Lipid Based Formulations. (Pubmed Central) -  Sep 11, 2019   
    ...Lipophilic (docusate) salt forms of erlotinib, gefitinib, ceritinib, and cabozantinib (as example smKIs demonstrating low aqueous solubility and high lipophilicity) were prepared and isolated as workable powder solids...Isolation as the lipophilic salt facilitated smKI loading in model lipid formulations at high concentration, increased in vitro solubilization at gastric and intestinal pH and in some cases increased oral absorption (~2-fold for cabozantinib formulations in rats). Application of a lipophilic salt approach can therefore facilitate the use of lipid-based formulations for examples of the smKI compound class where low solubility limits absorption and is a risk factor for increased variability due to food-effects.
  • ||||||||||  Review, Journal:  How I treat ALK-positive non-small cell lung cancer. (Pubmed Central) -  Aug 20, 2019   
    Herein, we attempt to answer these questions through the evidence-based interpretation of studies on ALK-rearranged NSCLC combined with experience gained from our institution. The authors also propose a therapeutic algorithm for the management of this complex and highly treatable disease to assist clinicians globally in the treatment of patients with ALK-positive NSCLC.
  • ||||||||||  Zykadia (ceritinib) / Novartis
    Pathology perspective: What are subepithelial lesions? (A2) -  Aug 18, 2019 - Abstract #UEGW2019UEGW_20;    
    In conclusion the diagnosis depends on the layer of the wall. Immunochistochemistry or Molecular Pathology may lead to confusing results if not correlated to the exact site within the wall and the morphology of the lesion.
  • ||||||||||  Alecensa (alectinib) / Roche
    Clinical, Journal:  Alectinib in the treatment of ALK-positive metastatic non-small cell lung cancer: clinical trial evidence and experience with a focus on brain metastases. (Pubmed Central) -  Aug 10, 2019   
    ...Crizotinib was the first ALK inhibitor developed and it demonstrated improved outcomes in patients with ALK-positive advanced NSCLC in comparison with chemotherapy...Because the most frequent mechanism of resistance is the development of a secondary ALK mutation, second (ceritinib, alectinib, brigatinib) and third-generation (lorlatinib) ALK inhibitors were developed...It was also shown to have high intracranial efficacy. In this article, we review clinical trial evidence of alectinib efficacy as well as publications reporting the experience of alectinib in daily practice, with a focus on brain metastases.
  • ||||||||||  cyclophosphamide intravenous / generics
    Journal:  Targeting ALK in pediatric RMS does not induce antitumor activity in vivo. (Pubmed Central) -  Aug 3, 2019   
    These observations suggests that complete and durable response can be safely obtained by using next generation ALK inhibitors in high risk patients ALK+ALCL with CNS relapse or progression. While ALK appears to be a relevant target in RMS in vitro, targeting this kinase in vivo yields no therapeutic efficacy, warranting extreme caution when considering the use of these agents in pediatric RMS patients.
  • ||||||||||  Review, Journal:  Canadian perspectives: update on inhibition of ALK-positive tumours in advanced non-small-cell lung cancer. (Pubmed Central) -  Aug 1, 2019   
    Canadian recommendations are therefore revised as follows:■ Patients with advanced nonsquamous nsclc have to be tested for the presence of an ALK rearrangement.■ Treatment-naïve patients with ALK-positive disease should initially be offered single-agent alectinib or ceritinib, or both sequentially.■ Crizotinib-refractory patients should be treated with single-agent alectinib or ceritinib, or both sequentially.■ Further treatments could include single-agent brigatinib or lorlatinib, or both sequentially.■ Patients progressing on alk tyrosine kinase inhibitors should be considered for pemetrexed-based chemotherapy.■ Other systemic therapies should be exhausted before immunotherapy is considered. Multiple lines of alk inhibition are now recommended for patients with advanced nsclc with an ALK rearrangement.
  • ||||||||||  Zykadia (ceritinib) / Novartis
    Enrollment change, Trial completion date, Trial withdrawal, Trial primary completion date, Metastases:  Ceritinib in Mutation and Oncogene Directed Therapy in Thyroid Cancer (clinicaltrials.gov) -  Jul 30, 2019   
    P2,  N=0, Withdrawn, 
    N=400 --> 160 N=100 --> 0 | Trial completion date: Dec 2021 --> Jan 2019 | Recruiting --> Withdrawn | Trial primary completion date: Dec 2020 --> Jan 2019
  • ||||||||||  Zykadia (ceritinib) / Novartis
    Enrollment closed, Trial completion date, Trial primary completion date, Combination therapy, Metastases:  Ceritinib in Combination With Stereotactic Ablative Radiation Metastatic Lung Adenocarcinoma (clinicaltrials.gov) -  Jul 30, 2019   
    P2,  N=33, Active, not recruiting, 
    N=100 --> 0 | Trial completion date: Dec 2021 --> Jan 2019 | Recruiting --> Withdrawn | Trial primary completion date: Dec 2020 --> Jan 2019 Recruiting --> Active, not recruiting | Trial completion date: Aug 2019 --> Aug 2021 | Trial primary completion date: Aug 2019 --> Aug 2020
  • ||||||||||  Clinical, Review, Journal:  Safety and Tolerability of Anaplastic Lymphoma Kinase Inhibitors in Non-Small-Cell Lung Cancer. (Pubmed Central) -  Jun 30, 2019   
    Furthermore, third-generation inhibitors are currently under development to overcome acquired resistance mechanisms inevitably resulting from treatment with first- and second-generation tyrosine kinase inhibitors. Therefore, this article aims to provide a comprehensive state-of-the-art review about the pharmacodynamics, pharmacokinetics, safety, and tolerability profiles of currently available and promising under-development anaplastic lymphoma kinase tyrosine kinase inhibitors.
  • ||||||||||  Zykadia (ceritinib) / Novartis, R-(-)-gossypol (AT 101) / Ascenta
    Journal:  Anaplastic Lymphoma Kinase Confers Resistance to BRAF Kinase Inhibitors in Melanoma. (Pubmed Central) -  Jun 24, 2019   
    Residual BRAFi and ALKi dual resistant melanoma cells from ceritinib-treated mice were sensitive to a broad-spectrum anti-apoptotic protein inhibitor, AT101. Collectively, our results provide a framework for treating BRAF-mutant melanoma that sequentially uses different targeted therapies based on post-treatment tumor evolution.
  • ||||||||||  Lorbrena (lorlatinib) / Pfizer, Xalkori (crizotinib) / Pfizer, Zykadia (ceritinib) / Novartis
    Clinical, Journal:  Capture-based ultra-deep sequencing in plasma ctDNA reveals the resistance mechanism of ALK inhibitors in a patient with advanced ALK-positive NSCLC. (Pubmed Central) -  Jun 20, 2019   
    Collectively, our results provide a framework for treating BRAF-mutant melanoma that sequentially uses different targeted therapies based on post-treatment tumor evolution. Clinical evidence and in vitro validation revealed the clinical usefulness of captured-base ultra-deep sequencing on longitudinal plasma ctDNA in revealing the underlying resistance mechanism and guiding the precise administration of ALK inhibitors in patients with advanced ALK-positive NSCLC.
  • ||||||||||  Retrospective data, Journal:  Anaplastic lymphoma kinase inhibitors in non-small cell lung cancer patients with brain metastases: a meta-analysis. (Pubmed Central) -  Jun 11, 2019   
    Five randomized studies assessed the intracranial efficacy of anti-ALK agents versus chemotherapy, the pooled RR for iORR was 3.54 (95% CI: 2.38-5.26), and the pooled HR for iPFS was 0.52 (95% CI: 0.36-0.75; P=0.71) estimated in 2 studies. Despite the limitation from lack of published clinical data, our results showed that ALK inhibitors are effective at the brain site regardless of previous anti-ALK treatments, systemic therapy with ALK inhibitors should be considered as a preferred approach over for controlling BMs from ALK-positive NSCLC.
  • ||||||||||  Zykadia (ceritinib) / Novartis, Pomalyst (pomalidomide) / Celgene
    Journal:  Chemically Induced Degradation of Anaplastic Lymphoma Kinase (ALK). (Pubmed Central) -  May 29, 2019   
    We demonstrate that in some cell types degrader potency is compromised by expression of drug transporter ABCB1. In addition, proteomic profiling demonstrated that these compounds also promote the degradation of additional kinases including PTK2 (FAK), Aurora A, FER, and RPS6KA1 (RSK1).
  • ||||||||||  Zykadia (ceritinib) / Novartis
    Journal:  Discovery of novel mutant-combating ALK and ROS1 dual inhibitors bearing imidazolidin-2-one moiety with reasonable PK properties. (Pubmed Central) -  May 29, 2019   
    Aiming to identify novel potent ALK and ROS1 dual inhibitors, the relatively bulky piperidine fragment in ceritinib was replaced with substituted imidazolidin-2-one moiety which gave rise to a series of 2,4-diaryl-aminopyrimidine (DAAP) analogs (6-33)...Importantly, pharmacokinetic (PK) profiles of 15 were obtained with quite satisfying AUC and C values. Besides, the binding models of 15 with ALK, ALK and ROS1 clearly present the essential interactions within the active site.
  • ||||||||||  SHP099 / Novartis, Lorbrena (lorlatinib) / Pfizer, Zykadia (ceritinib) / Novartis
    Journal:  SHP2 inhibition restores sensitivity in ALK-rearranged non-small-cell lung cancer resistant to ALK inhibitors. (Pubmed Central) -  May 22, 2019   
    Treatment with SHP099, the recently discovered small-molecule inhibitor of SHP2, in combination with the ALK tyrosine kinase inhibitor (TKI) ceritinib halted the growth of resistant PDCs through preventing compensatory RAS and ERK1 and ERK2 (ERK1/2) reactivation. These findings suggest that combined ALK and SHP2 inhibition may be a promising therapeutic strategy for resistant cancers driven by several different ALK-independent mechanisms underlying resistance.