Durvalumab

Durvalumab[2] (trade name Imfinzi) is an FDA-approved immunotherapy for cancer, developed by Medimmune/AstraZeneca.[3] It is a human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody that blocks the interaction of programmed cell death ligand 1 (PD-L1) with the PD-1 (CD279). Durvalumab is approved for the treatment of patients with locally advanced or metastatic urothelial carcinoma who either have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

Durvalumab
Monoclonal antibody
TypeWhole antibody
SourceHuman
TargetCD274
Clinical data
Trade namesImfinzi
Other namesMEDI4736
AHFS/Drugs.comMonograph
MedlinePlusa617030
License data
Pregnancy
category
  • AU: D [1]
  • US: N (Not classified yet) [1]
    Routes of
    administration    		IV
    ATC code
    Legal status
    Legal status
    Identifiers
    CAS Number
    PubChem CID
    IUPHAR/BPS
    DrugBank
    ChemSpider
    • none
    UNII
    KEGG
    Chemical and physical data
    FormulaC6502H10018N1742O2024S42
    Molar mass146.3 kg/mol g·mol−1

    Durvalumab is known as a checkpoint inhibitor drug.[4] The list price for the drug from AstraZeneca is $180,000 for a year.[5]

    Clinical trials

    A phase IB clinical trial of durvalumab and tremelimumab showed some activity in non-small cell lung cancer (NSCLC).[6] Phase 1 data in advanced metastatic urothelial bladder (Study 1108) has led to FDA breakthrough therapy designation.[4][7] Early results of a phase I trial combining durvalumab and gefitinib in lung cancer patients "showed promise".[8] A phase I clinical trial is currently underway using durvalumab with a TLR 7/8 agonist (MEDI 9197) for solid tumors.[9] A Phase 1b/2a trial is underway combining durvalumab with an HPV DNA vaccine (MEDI 0457) in patients with HPV-associated recurrent/metastatic head and neck cancer.[10]

    In July 2017, AstraZeneca announced that a phase III trial of durvalumab with tremelimumab as a first-line treatment of non-small cell lung cancer failed to meet its primary endpoint of progression-free survival.[11]

    In November 2017, the double-blinded phase III AstraZeneca PACIFIC clinical trial demonstrated the efficacy of durvalumab in the treatment of stage III non-small cell lung cancer.[12] 709 patients with stage III NSCLC who did not have disease progression after two or more cycles of a platinum-based chemotherapy were randomly assigned to receive durvalumab or a placebo as consolidation therapy for their lung cancer. Durvalumab increased the median progression-free survival from 5.6 months (placebo) to 16.8 months (durvalumab); the 12 month progression-free survival rate was increased from 35.3% (placebo) to 55.9% (durvalumab), and the 18 month progression-free survival rate was increased from 27.0% (placebo) to 44.2% (durvalumab).[4] The median time to death or distant metastases was also increased from 14.6 months (placebo) to 23.2 months (durvalumab). Extreme side effects were also increased from 26.1% of patients (placebo) to 29.9% of patients (durvalumab).

    References
    1. Use During Pregnancy and Breastfeeding
    2. World Health Organization (2014). "International Nonproprietary Names for Pharmaceutical Substances (INN). Proposed INN: List 112" (PDF). WHO Drug Information. 28 (4).
    3. Research, Center for Drug Evaluation and. "Approved Drugs - Durvalumab (Imfinzi)". www.fda.gov. Retrieved 6 May 2017.
    4. Syn, Nicholas L; Teng, Michele W L; Mok, Tony S K; Soo, Ross A (2017). "De-novo and acquired resistance to immune checkpoint targeting". The Lancet Oncology. 18 (12): e731–e741. doi:10.1016/s1470-2045(17)30607-1. PMID 29208439.
    5. "Cancer drugs are getting better and dearer". The Economist. Retrieved 19 May 2017.
    6. "Astrazeneca's combination of durvalumab with tremelimumab shows clinical activity in non-small cell lung cancer irrespective of PD-L1 status. Feb 2016".
    7. AstraZeneca's (AZN) Durvalumab Granted FDA Breakthrough Therapy Designation. StreeInsider.com Corporate News, FDA, Management Comments. 17 February 2016.
    8. "Promising Drug for Lung Cancer and Mesothelioma Patients". 19 May 2016.
    9. Clinical trial number NCT02556463 for "A Study of MEDI9197 in Subjects With Solid Tumors or CTCL and in Combination With Durvalumab and/or Palliative Radiation in Subjects With Solid Tumors" at ClinicalTrials.gov
    10. Clinical trial number NCT03162224? for "Safety and Efficacy of MEDI0457 and Durvalumab in Patients With HPV Associated Recurrent/Metastatic Head and Neck Cancer" at ClinicalTrials.gov
    11. "AstraZeneca reports initial results from the ongoing MYSTIC trial in Stage IV lung cancer". www.astrazeneca.com.
    12. "AstraZeneca presents superior progression-free survival for Imfinzi in the PACIFIC trial of patients with locally-advanced unresectable lung cancer at ESMO 2017 Congress". www.astrazeneca.com. September 2017.
    • "Durvalumab". Drug Information Portal. U.S. National Library of Medicine.
    This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.