Durvalumab

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

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