Zorifer (zorifertinib) / Alpha Biopharma, AstraZeneca 
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  • ||||||||||  Zorifer (zorifertinib) / Alpha Biopharma, AstraZeneca
    Journal:  The climb toward intracranial efficacy: Zorifertinib in EGFR-mutant NSCLC with CNS metastases in the EVEREST trial. (Pubmed Central) -  Jan 12, 2025   
    The study is registered on PROSPERO (CRD42024506995). The phase III EVEREST trial evaluating zorifertinib in the treatment of metastatic EGFR-mutant NSCLC was groundbreaking in its specific inclusion of patients with brain metastases.1 Zorifertinib prolonged systemic and intracranial progression-free survival compared with first-generation EGFR inhibitors, yet questions remain about its efficacy and toxicity compared with osimertinib.
  • ||||||||||  zorifertinib (AZD3759) / Alpha Biopharma, AstraZeneca
    P2 data, Journal:  Efficacy, safety and dose selection of AZD3759 in patients with (Pubmed Central) -  Oct 2, 2023   
    P2
    Sequential use of AZD3759 and third-generation EGFR-TKIs represents a new option. Chinese Thoracic Oncology Group (CTONG).
  • ||||||||||  zorifertinib (AZD3759) / Alpha Biopharma, AstraZeneca
    Journal:  Developing CuS for Predicting Aggressiveness and Prognosis in Lung Adenocarcinoma. (Pubmed Central) -  May 31, 2023   
    In conclusion, cuproptosis is involved in LUAD aggressiveness, and CuS can accurately predict the prognosis of patients. These findings provide a basis for precise treatment of patients with high CuS in LUAD.
  • ||||||||||  An individual patient-level meta-analysis of non () -  Apr 26, 2023 - Abstract #ASCO2023ASCO_6482;    
    ECOG performance status is an independent predictor of prognosis in these patients. These results highlight the need for prospective studies for this difficult to treat patient population.
  • ||||||||||  zorifertinib (AZD3759) / Alpha Biopharma, AstraZeneca
    Journal:  AZD3759 enhances radiation effects in non-small-cell lung cancer by a synergistic blockade of epidermal growth factor receptor and Janus kinase-1. (Pubmed Central) -  Feb 23, 2022   
    AZD3759 is a novel epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) on the basis of gefitinib and has been proven to enter the central nervous system...The present study aimed to compare the effects of AZD3759 and osimertinib on RA efficacy in NSCLC and explore the potential mechanism of action of AZD3759...The effects of AZD3759 on RA efficacy in PC-9 cells and in a brain metastasis animal model were significantly abolished by the overexpression of JAK1. Collectively, our results suggested that AZD3759 promoted RA antitumor effects in NSCLC by synergistic blockade of EGFR and JAK1.
  • ||||||||||  Zorifer (zorifertinib) / Alpha Biopharma, AstraZeneca
    Enrollment closed, Trial completion date, Trial primary completion date, Metastases:  EVEREST: First Line Treatment in EGFR Mutation Positive Advanced NSCLC Patients with Central Nervous System (CNS) Metastases (clinicaltrials.gov) -  Jul 12, 2021   
    P2/3,  N=492, Active, not recruiting, 
    As AZD3759 is already in the clinic, this paper's results suggest a possible repositioning of AZD3759 as a disease-modifying approach for PD. Recruiting --> Active, not recruiting | Trial completion date: Oct 2021 --> Nov 2022 | Trial primary completion date: Jun 2021 --> Aug 2022
  • ||||||||||  Selective vulnerability of GBM PDX to a panel of EGFR tyrosine kinase inhibitors (Virtual Meeting II: E-Posters) -  May 16, 2020 - Abstract #AACRII2020AACR-II_2319;    
    GBM76 had IC50 values of 1-8uM with all seven EGFR inhibitors including AZD3759...The drug response mechanism and its correlation with the mutation status of CDKN2A, EGFR, and PTEN will be further investigated cross a broad array of GBM PDX models. Supported by NIH NCI R01 CA204136
  • ||||||||||  Zorifer (zorifertinib) / Alpha Biopharma, AstraZeneca
    Enrollment closed, Trial completion date, Trial primary completion date:  AZD3759-001: Evaluate Safety, Tolerability, Pharmacokinetics and Anti-tumor Activity of AZD3759 (clinicaltrials.gov) -  Mar 24, 2020   
    P1/2,  N=15, Active, not recruiting, 
    Supported by NIH NCI R01 CA204136 Recruiting --> Active, not recruiting | Trial completion date: Jun 2020 --> Nov 2020 | Trial primary completion date: Jun 2020 --> Nov 2020
  • ||||||||||  Preclinical, Journal:  Brain distribution of a panel of EGFR inhibitors using cassette-dosing in wild-type and Abcb1/Abcg2 deficient mice. (Pubmed Central) -  Jan 25, 2020   
    Results show that the prediction of brain distribution based on physicochemical properties of a drug can be misleading, especially for compounds subject to extensive efflux transport. Moreover, this study informs the choice of EGFR inhibitors, i.e., determining BBB permeability combined with a known target potency, that may be effective in future clinical trials for brain tumors.
  • ||||||||||  Tagrisso (osimertinib) / AstraZeneca
    Journal:  Building on the success of osimertinib: achieving CNS exposure in oncology drug discovery. (Pubmed Central) -  Jan 19, 2020   
    Here, we discuss the oncology drug candidates AZD3759 and AZD1390 as case examples of discovery projects designing BBB penetrance. We demonstrate how these innovative kinase inhibitors were recognized as brain penetrant and outline our view of experimental approaches and strategies that can facilitate the discovery of new brain-penetrant therapies for the treatment of primary and secondary CNS malignancies as well as other CNS disorders.
  • ||||||||||  AZD3759 / AstraZeneca
    Journal:  AZD3759 induces apoptosis in hepatoma cells by activating a p53-SMAD4 positive feedback loop. (Pubmed Central) -  Oct 29, 2019   
    To the best of our knowledge, p53-induced SMAD4 transcription and SMAD4-determined the sub-location of p53 have not been reported. Taken together, our results demonstrated that AZD3759 might be an alternative strategy for HCC treatment and activating p53-SMAD4 positive feedback loop might enhance its therapeutic effects on HCC.
  • ||||||||||  AZD3759 / AstraZeneca
    PK/PD data, Preclinical, Journal:  Pharmacodynamic modelling of resistance to epidermal growth factor receptor inhibition in brain metastasis mouse models. (Pubmed Central) -  Aug 1, 2019   
    The developed model to describe resistance suggests that the resistance to EGFR-inhibition seen in these xenografts is best described by assuming a small percentage of cells are resistant to treatment at baseline. This model suggests changes to dosing and dosing schedule may not prevent resistance to treatment developing, and that additional treatments would need to be used in combination to overcome resistance.
  • ||||||||||  Zorifer (zorifertinib) / Alpha Biopharma, AstraZeneca
    Enrollment change, Trial completion date, Trial primary completion date:  AZD3759-001: Evaluate Safety, Tolerability, Pharmacokinetics and Anti-tumor Activity of AZD3759 (clinicaltrials.gov) -  May 29, 2019   
    P1/2,  N=21, Recruiting, 
    This model suggests changes to dosing and dosing schedule may not prevent resistance to treatment developing, and that additional treatments would need to be used in combination to overcome resistance. N=180 --> 21 | Trial completion date: Feb 2020 --> Jun 2020 | Trial primary completion date: Oct 2019 --> Jun 2020