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


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  • ||||||||||  Review, Journal, PD(L)-1 Biomarker, IO biomarker:  Treatment of Brain Metastases of Non-Small Cell Lung Carcinoma. (Pubmed Central) -  Mar 30, 2021   
    The I117N resistance mutation in patients with the ALK mutation treated with alectinib is overcome by ceritinib...This therapeutic option blocks the PD-1 receptor on the surface of T or B lymphocytes or PD-L1 located on cancer cells with an applicable antibody. Based on clinical trials, pembrolizumab and all antibodies are included in the treatment of non-small cell lung carcinoma with CNS metastases.
  • ||||||||||  Zykadia (ceritinib) / Novartis
    Journal:  Targeting Cysteine Located Outside the Active Site: An Effective Strategy for Covalent ALKi Design. (Pubmed Central) -  Mar 24, 2021   
    In addition, the molecule showed significant improvement of anticancer activities and potential antidrug resistant activity compared with Ceritinib, demonstrating the covalent inhibitor of ALK can be a promising drug candidate for the treatment of NSCLC. This work may provide a novel perspective on the design of covalent inhibitors.
  • ||||||||||  PK/PD data, Review, Journal:  Pharmacokinetic-Based Drug-Drug Interactions with Anaplastic Lymphoma Kinase Inhibitors: A Review. (Pubmed Central) -  Mar 16, 2021   
    These factors can result in increased risks for serious adverse events or can lead to reduced therapeutic effects of ALK-TKIs. This review characterizes and summarizes the pharmacokinetic parameters and drug--drug interactions associated with ALK-TKIs to provide specific recommendations for oncologists and clinical pharmacists when prescribing ALK-TKIs.
  • ||||||||||  TPX-0131 / Turning Point Therapeutics
    [VIRTUAL] TPX-0131, a potent inhibitor of wild type ALK and a broad spectrum of both single and compound ALK resistance mutations () -  Mar 11, 2021 - Abstract #AACR2021AACR_395;    
    In contrast, lorlatinib (5 mg/kg BID) caused 31% TGI in the G1202R/L1198F model and did not have statistically significant TGI in the G1202R/L1196M model. Taken together, TPX-0131 is a next generation ALK inhibitor that has preclinical potency against WT ALK as well as a broad spectrum of acquired resistance mutations, especially compound mutations, which currently lack any effective ALK inhibitor therapy.
  • ||||||||||  Trial completion date, Trial primary completion date, Metastases:  MatchMel: Molecular Profiling and Matched Targeted Therapy for Patients With Metastatic Melanoma (clinicaltrials.gov) -  Mar 9, 2021   
    P2,  N=1000, Not yet recruiting, 
    In conclusion, NUV-655 (NVL-655) offers a preclinical profile that addresses a medical need for ALK-positive NSCLC patients; it is a brain-penetrant and TRKB-sparing small-molecule inhibitor of ALK with activity against the solvent front drug-resistance mutations G1202R, G1202R/L1196M, and G1202R/G1269A. Trial completion date: Apr 2023 --> Dec 2028 | Trial primary completion date: Apr 2023 --> May 2027
  • ||||||||||  Trial completion date, Trial primary completion date, Metastases:  MatchMel: Molecular Profiling and Matched Targeted Therapy for Patients With Metastatic Melanoma (clinicaltrials.gov) -  Feb 25, 2021   
    P2,  N=1000, Not yet recruiting, 
    These in silico systems biology-based models could be applied for exploring other unanswered questions. Trial completion date: Sep 2022 --> Apr 2023 | Trial primary completion date: Sep 2022 --> Apr 2023
  • ||||||||||  Xalkori (crizotinib) / Pfizer, Zykadia (ceritinib) / Novartis, Alecensa (alectinib) / Roche
    [VIRTUAL] Predictors of treatment response in ALK-positive metastatic non-small cell lung cancer (ePoster Display) -  Feb 24, 2021 - Abstract #ELCC2021ELCC_370;    
    Also, we found the cut-off level of ALK positivity ratio in tumor cells for the response was 33% (p = 0.002, AUC:0.740, sensitivity 57.5%, specificity 78.3%).Conclusions In this study, we determined the real-life efficiency of ALK inhibitors in patients with ALK-positive NSCLC. We found that the high ALK positivity ratio, female gender, and having under three metastatic sites were positive predictive factors of ALK inhibitors’ response
  • ||||||||||  Clinical, Journal:  Clinical consequences of resistance to ALK inhibitors in non-small cell lung cancer. (Pubmed Central) -  Feb 20, 2021   
    The third-generation inhibitor lorlatininb is approved for patients who have developed resistance to any ALK inhibitor.Areas covered: In this review, an unstructured search in Pubmed and SCOPUS was conducted. We summarized the mechanisms of resistance to ALK inhibitors and its consequences in the treatment-decision making in advanced or metastatic NSCLC after failure to a first-line ALK inhibitor.Expert opinion: Currently, there are a growing number of options of therapeutic agents against ALK+ NSCLC (approved and in development); however, adequate selection and sequencing of agents is crucial to deal with the tumor evolution.
  • ||||||||||  Xalkori (crizotinib) / Pfizer, Zykadia (ceritinib) / Novartis, Alecensa (alectinib) / Roche
    Clinical, Observational data, Journal, Real-World Evidence:  Treatment Sequencing in Patients with Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer in Japan: A Real-World Observational Study. (Pubmed Central) -  Feb 2, 2021   
    Additional ALK TKIs have since been approved in Japan as first-line or later therapeutic options for patients with ALK-positive NSCLC, but the optimal sequence of ALK TKI usage remains undetermined. As new data continue to emerge, additional research will be warranted to evaluate ALK TKI sequences that do not include crizotinib as the first therapy in this patient population.
  • ||||||||||  Review, Journal:  How to select the best upfront therapy for metastatic disease? Focus on ALK-rearranged non-small cell lung cancer (NSCLC). (Pubmed Central) -  Jan 26, 2021   
    Ceritinib, another second-generation ALK inhibitor has been shown to be superior to chemotherapy in ALK-rearranged disease with good CNS activity...Lorlatinib, a third-generation ALK inhibitor, has demonstrated activity in the treatment naïve setting and in resistance to crizotinib and second-generation ALK inhibitors...Another new ALK inhibitor, ensartinib, has demonstrated efficacy in the first-line setting and in alectinib refractory disease. Additional studies are underway examining mechanisms of resistance and best treatment options post resistance.
  • ||||||||||  Review, Journal:  The Emerging Therapeutic Landscape of ALK Inhibitors in Non-Small Cell Lung Cancer. (Pubmed Central) -  Dec 30, 2020   
    The discovery of the EML4-ALK fusion gene in a limited subset of patients affected by NSCLC and the subsequent clinical development of crizotinib in 2011 has been an impressive milestone in lung cancer research...Afterward, modern tyrosine kinase inhibitors (TKIs), such as ceritinib, alectinib, brigatinib, and lorlatinib, have been approved by the Food and Drug Administration (FDA) for the management of anaplastic lymphoma kinase (ALK)-positive NSCLCs...In this review, we provide a comprehensive overview of the state-of-the-art targeted therapy options in ALK-positive NSCLCs. Resistance, potential therapeutic strategies to overcome drug resistance, and future perspectives for this subset of patients are critically analyzed and summarized.
  • ||||||||||  Xalkori (crizotinib) / Pfizer, Zykadia (ceritinib) / Novartis
    Preclinical, Journal:  Revealing acquired resistance mechanisms of kinase-targeted drugs using an on-the-fly, function-site interaction fingerprint approach. (Pubmed Central) -  Dec 23, 2020   
    Additionally, we find that the L1196M mutation does not simply alter the binding modes of inhibitors, but also affects the flexibility of the entire ALK kinase domain. Our work provides an understanding of the mechanisms of ALK drug resistance, confirms the usefulness of the on-the-fly Fs-IFP approach and provides a practical paradigm to study drug-resistance mechanisms in prospective drug discovery.
  • ||||||||||  Lorbrena (lorlatinib) / Pfizer, Zykadia (ceritinib) / Novartis, Alunbrig (brigatinib) / Takeda
    [VIRTUAL] Real-World First Line Targeted Therapy Duration Following ctDNA Testing in Advanced Non-Small Cell Lung Cancer (ePoster Hall) -  Dec 17, 2020 - Abstract #IASLCWCLC2020IASLC_WCLC_1626;    
    In this largest real-world series of similar subjects to date, duration ofEGFR and ALK targeted therapy was comparable in claims data to duration of treatment based on tissue molecular testing. These data demonstrate that first line targeted aNSCLC treatment based on a well-validated, comprehensive ctDNA test (Guardant360) has similar outcomes to tissue guided first line targeted therapy.
  • ||||||||||  [VIRTUAL] Treatment Options for Patients with Brain Metastases in Oncogene-Driven Non-Small Cell Lung Cancer (ePoster Hall) -  Dec 17, 2020 - Abstract #IASLCWCLC2020IASLC_WCLC_1560;    
    Newly developed TKIs achieved a partial or complete CNS response in 42.9%. Conclusion Our study shows that deferring CNS RT in oncogene-driven NSCLC and CNS involvement is a valid option due to CNS metastases response to TKIs, especially to those that can penetrate the blood-brain barrier, in order to avoid side-effects derived from CNS radiation.
  • ||||||||||  Xalkori (crizotinib) / Pfizer, Zykadia (ceritinib) / Novartis, Alunbrig (brigatinib) / Takeda
    [VIRTUAL] Organoid Used as Preclinical Modal in ALK Inhibitor Selection: Report of a Case Harbouring LRRTM4–ALK Fusion (ePoster Hall) -  Dec 17, 2020 - Abstract #IASLCWCLC2020IASLC_WCLC_1554;    
    No other oncogenic mutation was detected in this patient, and we speculated that this novel LRRTM4–ALK fusion served as the driver mutation for the patient’s cancer. Our results suggest that ALK tyrosine-kinase inhibitors might be effective for the treatment of tumors with this novel fusion gene.
  • ||||||||||  Alunbrig (brigatinib) / Takeda
    [VIRTUAL] First-line Brigatinib in Anaplastic Lymphoma Kinase-positive Non-small Cell Lung Cancer: A Network Meta-Analysis (ePoster Hall) -  Dec 17, 2020 - Abstract #IASLCWCLC2020IASLC_WCLC_1546;    
    Conclusion Brigatinib significantly prolonged PFS in ALK inhibitor-naïve patients with ALK-positive NSCLC compared with ceritinib, crizotinib, and chemotherapy and was at least as effective as alectinib in reducing the risk of progression, suggesting that brigatinib is an effective 1L treatment. The results also suggest strong efficacy of brigatinib in patients with CNS metastases.
  • ||||||||||  Zykadia (ceritinib) / Novartis, CI-1040 / Pfizer
    Preclinical, Journal:  A mass spectrometry-based proteome map of drug action in lung cancer cell lines. (Pubmed Central) -  Dec 16, 2020   
    Aggregating drug response across cell lines also revealed that one-quarter of compounds modulated the abundance of one of their known protein targets. Finally, the proteomic data led us to discover that inhibition of mitochondrial function is an off-target mechanism of the MAP2K1/2 inhibitor PD184352 and that the ALK inhibitor ceritinib modulates autophagy.
  • ||||||||||  Zykadia (ceritinib) / Novartis
    Trial completion:  Preoperative Ceritinib (LDK378) in Glioblastoma Multiforme and CNS Metastasis (clinicaltrials.gov) -  Dec 11, 2020   
    P1,  N=10, Completed, 
    Finally, the proteomic data led us to discover that inhibition of mitochondrial function is an off-target mechanism of the MAP2K1/2 inhibitor PD184352 and that the ALK inhibitor ceritinib modulates autophagy. Active, not recruiting --> Completed