MYSTIC Trial, Evaluating Durvalumab as First-Line in NSCLC, Adds OS Endpoint

A phase III trial evaluating the effect of the programmed death ligand-1 (PD-L1) inhibitor durvalumab, alone or in combination with tremelimumab, versus platinum-based chemotherapy, has refined its endpoints to include overall survival (OS) along with progression-free survival (PFS).

The randomized, multi-center, open-label trial, called MYSTIC, was designed to test whether durvalumab can be used as front-line treatment in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC), who express wild-type epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) and PD-L1. The original primary outcome measure was PFS at 3 years, while secondary outcome measures include health-related quality of life, pharmacokinetics of the drugs, and immunogenicity of the biologicals durvalumab and tremelimumab.

In a press release, AstraZeneca, which is developing the drug, said that the decision to include OS as an endpoint “is based on recent internal and external data, including durvalumab’s strong efficacy in monotherapy presented at recent medical meetings, as well as significant opportunities in the competitive landscape.” This update will extend OS data collection to 2018, while PFS data are expected in mid-2017, in addition to several interim analyses for OS.

The company is simultaneously testing durvalumab as monotherapy (PEARL trial) or in combination with tremelimumab (NEPTUNE trial) against standard-of-care platinum-based chemotherapy, in patients with EGFR and ALK wild-type advanced or metastatic NSCLC.

“The MYSTIC trial amendments, the NEPTUNE trial expansion, and initiation of the new PEARL trial are all designed to enhance our options in 1st-line NSCLC for IO-IO combination as well as for IO monotherapy. We continue to follow the science through both internal and external sources for the benefit of patients and look forward to sharing our first pivotal data in mid-2017,” Sean Bohen, executive vice president, Global Medicines Development and CMO at AstraZeneca, said in the press release.

Durvalumab is a PD-L1 inhibitor that received breakthrough designation for use in bladder cancer early last year. By interacting with both, the programmed death-1 receptor and CD80 on T cells, it boosts the immune system’s tumor-detecting capacity. AstraZeneca is also evaluating this antibody in head and neck cancer, liver cancer, and blood cancer.