“Durvalumab”的意思、由来-开放百科全书

Durvalumab^[1] (trade name Imfinzi) 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

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

1. ^{{cite journal | author = World Health Organization | title = International Nonproprietary Names for Pharmaceutical Substances (INN). Proposed INN: List 112 | journal = WHO Drug Information | volume = 28 | issue = 4 | year = 2014 | url = http://www.who.int/medicines/publications/druginformation/innlists/PL112.pdf | format=PDF}}
2. ^{{Cite web|url=https://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm555930.htm|title=Approved Drugs - Durvalumab (Imfinzi)|last=Research|first=Center for Drug Evaluation and|website=www.fda.gov|language=en|access-date=2017-05-06}}
3. ^¹²{{Cite journal|last=Syn|first=Nicholas L|last2=Teng|first2=Michele W L|last3=Mok|first3=Tony S K|last4=Soo|first4=Ross A|title=De-novo and acquired resistance to immune checkpoint targeting|url=http://linkinghub.elsevier.com/retrieve/pii/S1470204517306071|journal=The Lancet Oncology|language=en|volume=18|issue=12|pages=e731–e741|doi=10.1016/s1470-2045(17)30607-1}}
4. ^{{Cite web|url=https://www.economist.com/news/business/21721676-astrazenecas-imfinzi-costs-180000-years-treatment-cancer-drugs-are-getting-better-and|title=Cancer drugs are getting better and dearer|website=The Economist|access-date=2017-05-19}}
5. ^{{cite web|url=http://seekingalpha.com/pr/16108396-astrazeneca-s-combination-durvalumab-tremelimumab-shows-clinical-activity-non-small-cell-lung|title=Astrazeneca’s combination of durvalumab with tremelimumab shows clinical activity in non-small cell lung cancer irrespective of PD-L1 status. Feb 2016|publisher=}}
6. ^AstraZeneca's (AZN) Durvalumab Granted FDA Breakthrough Therapy Designation. StreeInsider.com Corporate News, FDA, Management Comments. February 17, 2016.
7. ^{{cite web|url=https://www.mesotheliomahelp.org/2016/05/clinical-trial-points-promising-drug-combo-lung-cancer-mesothelioma-patients-42357/|title=Promising Drug for Lung Cancer and Mesothelioma Patients|date=19 May 2016|publisher=}}
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. ^{{cite web|url=https://www.astrazeneca.com/media-centre/press-releases/2017/astrazeneca-reports-initial-results-from-the-ongoing-mystic-trial-in-stage-iv-lung-cancer-27072017.html|title=AstraZeneca reports initial results from the ongoing MYSTIC trial in Stage IV lung cancer|website=www.astrazeneca.com}}
11. ^{{cite web|url=https://www.astrazeneca.com/media-centre/press-releases/2017/astrazeneca-presents-superior-progression-free-survival-for-imfinzi-in-the-pacific-trial-of-patients-with-locally-advanced-unresectable-lung-cancer-at-esmo-2017-congress-08092017.html|title=AstraZeneca presents superior progression-free survival for Imfinzi in the PACIFIC trial of patients with locally-advanced unresectable lung cancer at ESMO 2017 Congress|date=Sep 2017|publisher=|website=www.astrazeneca.com}}