Durvalumab

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Durvalumab
Monoclonal antibody
Type Whole antibody
Source Human
Target CD274
Clinical data
Trade names Imfinzi
Synonyms MEDI4736
ATC code
Identifiers
CAS Number
IUPHAR/BPS
DrugBank
ChemSpider
  • none
UNII
KEGG
Chemical and physical data
Formula C6502H10018N1742O2024S42
Molar mass 146.3 kg/mol

Durvalumab[1] is an FDA-approved immunotherapy for cancer, developed by Medimmune/AstraZeneca.[2] 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 and CD80 (B7.1) molecules. 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 is known as a checkpoint inhibitor drug.[3] The list price for the drug from AstraZeneca is $180,000 for a year.[4]

Clinical trials[edit]

A phase 1B clinical trial of durvalumab and tremelimumab showed some activity in non-small cell lung cancer (NSCLC).[5] Phase 1 data in advanced metastatic urothelial bladder (Study 1108) has led to FDA breakthrough therapy designation.[3][6] Early results of a phase I trial combining durvalumab and gefitinib in lung cancer patients "showed promise".[7] A Phase 1 clinical trial is currently underway using durvalumab with a TLR 7/8 agonist (MEDI 9197) for solid tumors.[8] 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.[9]

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.[10]

In November 2017, the double-blinded phase 3 AstraZeneca PACIFIC clinical trial demonstrated the efficacy of durvalumab in the treatment of stage III non-small cell lung cancer.[11] 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).[3] 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[edit]

  1. ^ World Health Organization (2014). "International Nonproprietary Names for Pharmaceutical Substances (INN). Proposed INN: List 112" (PDF). WHO Drug Information. 28 (4). 
  2. ^ Research, Center for Drug Evaluation and. "Approved Drugs - Durvalumab (Imfinzi)". www.fda.gov. Retrieved 2017-05-06. 
  3. ^ a b c Syn, Nicholas L; Teng, Michele W L; Mok, Tony S K; Soo, Ross A. "De-novo and acquired resistance to immune checkpoint targeting". The Lancet Oncology. 18 (12): e731–e741. doi:10.1016/s1470-2045(17)30607-1. 
  4. ^ "Cancer drugs are getting better and dearer". The Economist. Retrieved 2017-05-19. 
  5. ^ "Astrazeneca's combination of durvalumab with tremelimumab shows clinical activity in non-small cell lung cancer irrespective of PD-L1 status. Feb 2016". 
  6. ^ AstraZeneca's (AZN) Durvalumab Granted FDA Breakthrough Therapy Designation. StreeInsider.com Corporate News, FDA, Management Comments. February 17, 2016.
  7. ^ "Promising Drug for Lung Cancer and Mesothelioma Patients". 19 May 2016. 
  8. ^ https://clinicaltrials.gov/ct2/show/NCT02556463?term=medi9197&rank=1/ A Study of MEDI9197 in Subjects With Solid Tumors or CTCL and in Combination With Durvalumab and Palliative Radiation in Subjects With Solid Tumors
  9. ^ https://clinicaltrials.gov/ct2/show/NCT03162224?cond=INO+3112&rank=3 Safety and Efficacy of MEDI0457 and Durvalumab in Patients With HPV Associated Recurrent/Metastatic Head and Neck Cancer
  10. ^ "AstraZeneca reports initial results from the ongoing MYSTIC trial in Stage IV lung cancer". www.astrazeneca.com. 
  11. ^ "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. Sep 2017.