Positive efficacy and safety data have been reported for durvalumab (AstraZeneca/MedImmune) in two cohorts of patients with either advanced non–small-cell lung cancer (NSCLC) or advanced head-and-neck squamous cell carcinoma (HNSCC).
Durvalumab is an investigational human monoclonal antibody directed against programmed death ligand-1 (PD-L1) and is designed to help activate the immune system against tumors. Durvalumab blocks PD-L1 interaction with programmed death-1 (PD-1) and the costimulatory ligand CD80 on T cells, which maximizes T-cell activation. By inhibiting PD-L1, durvalumab helps increase T-cell activity against tumors to counter their efforts to evade the immune system.
Follow-up results from a phase 1/2 study of durvalumab as monotherapy in patients with advanced NSCLC showed that those with high programmed death ligand-1 (PD-L1)-expressing tumors had a higher objective response rate (ORR) and overall survival (OS) compared with patients with low or no PD-L1 expression. The ORR was 25% in patients with high PD-L1 tumors (n = 154) compared with 6% in patients with low PD-L1 tumors (n = 116). In those with high-PD-L1 expression, OS was 80%, 69%, and 66% in those receiving one line of therapy (n = 58), two lines of therapy (n = 179), or three or more lines of therapy (n = 250), respectively. OS in the group with low PD-L1 expression was 56%, 66%, and 53%, respectively.
In the cohort with metastatic/recurrent HNSCC (n = 62), all of the evaluable patients showed an ORR of 11%; this increased to 18% in patients with high PD-L1 tumors (n = 22). OS was 62% and 42% in all evaluable patients at six and 12 months, respectively.
AstraZeneca is developing durvalumab as the primary molecule in a combination-focused approach to strengthening the immune system against cancer. In 2015, durvalumab received a fast-track designation from the FDA for the treatment of patients with PD-L1–positive metastatic HNSCC, and in 2016, it was granted breakthrough therapy status for the treatment of patients with PD-L1–positive inoperable or metastatic urothelial bladder cancer whose tumors has progressed during or after one standard platinum-based regimen.
Source: PipelineReview; October 11, 2016.