Durvalumab is an FDA-approved immunotherapy for cancer, developed by Medimmune/AstraZeneca. It is a human immunoglobulin G1 kappa monoclonal antibody that blocks the interaction of programmed cell death ligand 1 with the PD-1. The US FDA has approved durvalumab for certain types of bladder and lung cancer:
Adult 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 IB clinical trial of durvalumab and tremelimumab showed some activity in non-small cell lung cancer. Phase 1 data in advanced metastatic urothelial bladder has led to FDAbreakthrough therapy designation. Early results of a phase I trial combining durvalumab and gefitinib in lung cancer patients "showed promise". A phase I clinical trial is currently underway using durvalumab with a TLR 7/8 agonist for solid tumors. A Phase 1b/2a trial is underway combining durvalumab with an HPVDNA vaccine 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 III 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 to 16.8 months ; the 12 month progression-free survival rate was increased from 35.3% to 55.9%, and the 18 month progression-free survival rate was increased from 27.0% to 44.2%. The median time to death or distant metastases was also increased from 14.6 months to 23.2 months. Extreme side effects were also increased from 26.1% of patients to 29.9% of patients.
