Durvalumab

Durvalumab[4] (trade name Imfinzi) is an FDA-approved immunotherapy for cancer, developed by Medimmune/AstraZeneca.[5] 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
Antigen-binding fragment of durvalumab (pale green) in complex with PD-L1 (pink). PDB: 5X8M.
Monoclonal antibody
TypeWhole antibody
SourceHuman
TargetCD274
Clinical data
Trade namesImfinzi
Other namesMEDI4736, MEDI-4736
AHFS/Drugs.comMonograph
MedlinePlusa617030
License data
Pregnancy
category
Routes of
administration
Intravenous
ATC code
Legal status
Legal status
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
  • none
UNII
KEGG
Chemical and physical data
FormulaC6502H10018N1742O2024S42
Molar mass146322.36 g·mol−1

Durvalumab is known as a checkpoint inhibitor drug.[6]

Medical uses

The US Food and Drug Administration (FDA) has approved durvalumab for certain types of bladder and lung cancer:[2]

  • Adults 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.
  • Adults with unresectable, Stage III non-small cell lung cancer whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy.
  • In combination with etoposide and either carboplatin or cisplatin, as first-line treatment for adults with extensive-stage small cell lung cancer.

Clinical trials

A phase IB clinical trial of durvalumab and tremelimumab showed some activity in non-small cell lung cancer (NSCLC).[7] Phase 1 data in advanced metastatic urothelial bladder (Study 1108) has led to FDA breakthrough therapy designation.[6][8] Early results of a phase I trial combining durvalumab and gefitinib in lung cancer patients "showed promise".[9] A phase I clinical trial is currently underway using durvalumab with a TLR 7/8 agonist (MEDI 9197) for solid tumors.[10] 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.[11]

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.[12]

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.[13] 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).[6] 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. "Durvalumab (Imfinzi) Use During Pregnancy". Drugs.com. 30 August 2019. Retrieved 7 February 2020.
  2. "Imfinzi- durvalumab injection, solution". DailyMed. 5 June 2020. Retrieved 30 September 2020.
  3. "Imfinzi EPAR". European Medicines Agency (EMA). Retrieved 30 September 2020.
  4. World Health Organization (2014). "International Nonproprietary Names for Pharmaceutical Substances (INN). Proposed INN: List 112" (PDF). WHO Drug Information. 28 (4).
  5. Research, Center for Drug Evaluation and. "Approved Drugs - Durvalumab (Imfinzi)". www.fda.gov. Retrieved 6 May 2017.
  6. 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.
  7. "Astrazeneca's combination of durvalumab with tremelimumab shows clinical activity in non-small cell lung cancer irrespective of PD-L1 status. Feb 2016".
  8. AstraZeneca's (AZN) Durvalumab Granted FDA Breakthrough Therapy Designation. StreeInsider.com Corporate News, FDA, Management Comments. 17 February 2016.
  9. "Promising Drug for Lung Cancer and Mesothelioma Patients". 19 May 2016.
  10. 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
  11. 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
  12. "AstraZeneca reports initial results from the ongoing MYSTIC trial in Stage IV lung cancer". www.astrazeneca.com.
  13. "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.
  • "Durvalumab". NCI Drug Dictionary. National Cancer Institute.</ref>
  • "Durvalumab". National Cancer Institute.
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