Durvalumab (trade name Imfinzi) is an FDA-approved immunotherapy for cancer, developed by Medimmune/AstraZeneca. 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.
A phase 1B clinical trial of durvalumab and tremelimumab showed some activity in non-small cell lung cancer (NSCLC). Phase 1 data in advanced metastatic urothelial bladder (Study 1108) has led to FDA breakthrough therapy designation. Early results of a phase I trial combining durvalumab and gefitinib in lung cancer patients "showed promise". A Phase 1 clinical trial is currently underway using durvalumab with a TLR 7/8 agonist (MEDI 9197) for solid tumors. 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.
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.
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. 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). 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).
- AstraZeneca's (AZN) Durvalumab Granted FDA Breakthrough Therapy Designation. StreeInsider.com Corporate News, FDA, Management Comments. February 17, 2016.
- 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
- 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
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