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


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  • ||||||||||  NVL-655 / Nuvalent, Alecensa (alectinib) / Roche
    Preclinical intracranial activity of NVL-655 in an alectinib-resistant patient-derived model harboring EML4-ALK fusion with G1202R mutation (Section 20; Poster Board #19) -  Mar 14, 2023 - Abstract #AACR2023AACR_6212;    
    P1/2
    Using a xenograft model derived from an alectinib-relapsed patient, we showed that NVL-655 had high intracranial activity against brain tumors bearing the ALK G1202R mutation that confers resistance to multiple ALK TKIs. NVL-655 is being evaluated in a Phase 1/2 clinical trial for patients with advanced NSCLC and other solid tumors harboring ALK rearrangement or activating ALK mutation (ALKOVE-1): NCT05384626.
  • ||||||||||  patritumab deruxtecan (U3-1402) / Daiichi Sankyo
    The impact of HER3 dynamics on the efficacy of HER3-DXd, a novel HER3 directed antibody-drug conjugate (Section 19; Poster Board #19) -  Mar 14, 2023 - Abstract #AACR2023AACR_6070;    
    HER3 expression was dynamically changed by HER3-DXd dosing regimen and by RTKi treatment, resulting in a substantial impact on payload release. These findings support our strategy of clinical studies using HER3-DXd after drugs that increase HER3 expression including EGFR TKI and indicate that HER3 dynamics may play a key role in achieving optimal efficacy of HER3-DXd.
  • ||||||||||  Xalkori (crizotinib) / Pfizer, Zykadia (ceritinib) / Novartis
    Treatment-free remission after discontinuation of ALK tyrosine kinase inhibitors (TKIs) in patients with ALK-positive anaplastic large cell lymphoma (ALCL) (Section 40; Poster Board #23) -  Mar 14, 2023 - Abstract #AACR2023AACR_3476;    
    MRD-guideddiscontinuation decision may be considered for ALK-positive ALCL patients treated with ALK inhibitors who had undetectable MRD.Table 1. Summary of patient characteristics and outcomes of ALK TKI discontinuationNo.SexAge at diagnosisAnn Arbor stageALK TKILines of prior therapyTreatment duration of ALK TKI (months)Reason for cessationDuration of ALK TKI cessation (months)Best response to ALK TKITime of MRD assessment after TKI cessationMRD after TKI cessation1M22IIBCrizotinib393.9Fertility27.8CR5.6Negative2F20IVBCrizotinib190.9Fertility25.9CR0.0Negative3M23IVCeritinib142.7Adverse event61.9CR61.9Negative4F58IVCrizotinib31.7Cost86.6CR72.1Negative5F64IVBCrizotinib113.6Cost31.0CR14.4Negative6M75IVCrizotinib211.7Cost80.2CR62.0Negative
  • ||||||||||  Zykadia (ceritinib) / Novartis
    ALK amplification and rearrangements are recurrent targetable events in congenital and adult glioblastoma (Room W307 - Convention Center) -  Mar 14, 2023 - Abstract #AACR2023AACR_3232;    
    Summary of patient characteristics and outcomes of ALK TKI discontinuationNo.SexAge at diagnosisAnn Arbor stageALK TKILines of prior therapyTreatment duration of ALK TKI (months)Reason for cessationDuration of ALK TKI cessation (months)Best response to ALK TKITime of MRD assessment after TKI cessationMRD after TKI cessation1M22IIBCrizotinib393.9Fertility27.8CR5.6Negative2F20IVBCrizotinib190.9Fertility25.9CR0.0Negative3M23IVCeritinib142.7Adverse event61.9CR61.9Negative4F58IVCrizotinib31.7Cost86.6CR72.1Negative5F64IVBCrizotinib113.6Cost31.0CR14.4Negative6M75IVCrizotinib211.7Cost80.2CR62.0Negative These findings support expanded evaluation of brain-penetrant ALK inhibitors in clinical trials across infant, pediatric, and adult GBMs.
  • ||||||||||  Zykadia (ceritinib) / Novartis, SNS-032 / Viracta Therap
    Journal:  Piperlongumine conjugates induce targeted protein degradation. (Pubmed Central) -  Feb 27, 2023   
    Mechanistically, we identified KEAP1 as the E3 ligase recruited by 955 to degrade CDK9 through a TurboID-based proteomics study, which was further confirmed by KEAP1 knockout and the nanoBRET ternary complex formation assay. In addition, PL-ceritinib conjugate can degrade EML4-ALK fusion oncoprotein, suggesting that PL may have a broader application as a covalent E3 ligase ligand in targeted protein degradation.
  • ||||||||||  Platform Trials (Walter E. Washington Convention Center, West Salon G-I (Street Level)) -  Feb 27, 2023 - Abstract #ATS2023ATS_259;    
    This TKI showed remarkable activity against L2026M and S1986Y likewise, however both mutants were refractory to entrectinib, crizotinib, repotrectinib and ceritinib. These results were confirmed by western blot.
  • ||||||||||  Retrospective data, Review, Journal, Metastases:  Comparative Efficacy of ALK Inhibitors for Treatment-Na (Pubmed Central) -  Feb 12, 2023   
    While lorlatinib was superior to brigatinib for PFS in the overall patient population, no significant difference between the two was found in the subgroup of patients with CNS metastases. These results can serve as a foundation for basic, clinical, and translational research and guide clinical oncologists in developing individualized treatment strategies for patients with ALK-p, ALK inhibitor-naive advanced NSCLC.
  • ||||||||||  Zykadia (ceritinib) / Novartis, Kisqali (ribociclib) / Novartis
    Enrollment change, Trial completion date, Trial termination, Trial primary completion date:  NEPENTHE: Next Generation Personalized Neuroblastoma Therapy (clinicaltrials.gov) -  Feb 2, 2023   
    P1,  N=66, Terminated, 
    In this article, we use a statistical approach to compare the efficacy and safety of targeted drugs that have been used in the first-line treatment of anaplastic lymphoma kinase mutations to improve the reference for clinicians to make treatment decisions in the real world. N=131 --> 66 | Trial completion date: Jun 2024 --> Aug 2022 | Recruiting --> Terminated | Trial primary completion date: Jun 2023 --> Aug 2022; The goals of Part 1 (molecular screening) were met, but lack of therapies to match molecular aberrations made Part 2 (treatment) no longer feasible.
  • ||||||||||  Zykadia (ceritinib) / Novartis
    Enrollment closed, Enrollment change, Trial completion date, Trial primary completion date, Metastases:  Ceritinib Plus Docetaxel in ALK-Negative, EGFR WT Advanced NSCLC (clinicaltrials.gov) -  Jan 31, 2023   
    P1,  N=21, Active, not recruiting, 
    N=131 --> 66 | Trial completion date: Jun 2024 --> Aug 2022 | Recruiting --> Terminated | Trial primary completion date: Jun 2023 --> Aug 2022; The goals of Part 1 (molecular screening) were met, but lack of therapies to match molecular aberrations made Part 2 (treatment) no longer feasible. Recruiting --> Active, not recruiting | N=48 --> 21 | Trial completion date: Oct 2024 --> May 2025 | Trial primary completion date: Oct 2023 --> May 2025
  • ||||||||||  Xalkori (crizotinib) / Pfizer, Zykadia (ceritinib) / Novartis, Alecensa (alectinib) / Roche
    Journal, HEOR, Real-world evidence, Real-world, Metastases:  Real-World Treatment and Outcomes of ALK-Positive Metastatic Non-Small Cell Lung Cancer in a Southeast Asian Country. (Pubmed Central) -  Jan 21, 2023   
    Patients who received ALK inhibitors as first-line therapy had significantly longer TOT (median of 11 months for first-generation inhibitors, not reached for second-generation inhibitors at the time of analysis) compared to chemotherapy (median of 2 months; P<0.01). Patients on ALK inhibitors had longer median OS and significantly longer TOT compared to chemotherapy, suggesting long-term benefit.
  • ||||||||||  Zykadia (ceritinib) / Novartis, Mekinist (trametinib) / Novartis, BeiGene
    Trial primary completion date:  Study of Trametinib + Ceritinib in Patients With Unresectable Melanoma (clinicaltrials.gov) -  Jan 20, 2023   
    P1,  N=27, Active, not recruiting, 
    Patients on ALK inhibitors had longer median OS and significantly longer TOT compared to chemotherapy, suggesting long-term benefit. Trial primary completion date: Apr 2023 --> Oct 2023
  • ||||||||||  Zykadia (ceritinib) / Novartis
    Journal:  FAT4 activation inhibits epithelial-mesenchymal transition (EMT) by promoting autophagy in H2228/Cer cells. (Pubmed Central) -  Dec 29, 2022   
    Furthermore, we found the regulatory action of FAT4 on autophagy was related to proteasome 26S subunit ubiquitin receptor and non-ATPase 4 (PSMD4) and proteasome 20S subunit beta 4 (PSMB4), and the inhibitory effect of autophagy on EMT might be related to ROS/NF-κB/IκB-α and Wnt/β-catenin pathways. In conclusion, FAT4 activation can inhibit the process of EMT in H2228/Cer cells by promoting autophagy, which provides a potential target for ceritinib-resistant ALK positive NSCLC therapy.
  • ||||||||||  Zykadia (ceritinib) / Novartis, Mekinist (trametinib) / Novartis
    P1 data, Journal, Metastases:  Phase 1 Study of Ceritinib Combined With Trametinib in Patients With Advanced ALK- or ROS1-Positive NSCLC. (Pubmed Central) -  Dec 23, 2022   
    P1/2
    Data from this trial indicate that the combination of ceritinib and trametinib had no unexpected toxicities and that a tolerable dose could be identified. A subset of patients seemed to obtain clinical benefit from this treatment after progression on prior ALK/ROS1 inhibitor treatment.ClinicalTrials.gov Identifier: NCT03087448.
  • ||||||||||  Journal, PD(L)-1 Biomarker, IO biomarker:  Pathological complete remission in ALK-positive lung cancer patient after multiple lines of conversion therapy. (Pubmed Central) -  Dec 17, 2022   
    Then the patient received the sixth line of treatment, camrelizumab/lorlatinib, for 9 antitumor cycles, resulting in PR...To our knowledge, this is the first documented case of cCR in a patient with ALK-positive advanced lung adenocarcinoma treated with multiple lines of therapy followed by surgical treatment. This case reveals the possible survival benefit of immunotherapy after multiple line treatment in ALK-positive advanced lung adenocarcinoma, indicating that it is possible find new therapeutic targets based on NGS molecular detection and provide precise therapeutic strategies for clinical practice when drug resistance or progression occurs in cancer therapy.
  • ||||||||||  Zykadia (ceritinib) / Novartis, Mekinist (trametinib) / Novartis, BeiGene
    Trial primary completion date:  Study of Trametinib + Ceritinib in Patients With Unresectable Melanoma (clinicaltrials.gov) -  Nov 14, 2022   
    P1,  N=27, Active, not recruiting, 
    More research is needed when longer follow-up data are available for later-generation ALK TKI, to fully understand ALK TKI sequencing and its effect on patient survival in a real-world setting. Trial primary completion date: Dec 2022 --> Apr 2023
  • ||||||||||  Lorbrena (lorlatinib) / Pfizer
    Journal, Tumor Mutational Burden, IO biomarker:  Lorlatinib and compound mutations in ALK+ large-cell neuroendocrine lung carcinoma: a case report. (Pubmed Central) -  Nov 2, 2022   
    Despite early progression within 3 mo under crizotinib, a durable response was achieved with alectinib...Another rebiopsy revealed ALK:p.L1196M, but the tumor did not respond to brigatinib or carboplatin/pemetrexed, before stabilization under lorlatinib...Lorlatinib retained efficacy in the heavily pretreated setting, while its upfront use could possibly have prevented the stepwise emergence of compound ALK mutations. Furthermore, the disease course was more aggressive and OS shorter compared to the V2/TP53wt ALK+ lung adenocarcinoma, while crizotinib, ceritinib and brigatinib did not confer the benefit expected according to NGS results, which also underline the need for more potent drugs against ALK in the high-risk setting of neuroendocrine histology.