AstraZeneca has expanded a late-stage trial currently assessing a potential new immuno-oncology (IO) therapy combination for the first-line treatment of non-small cell lung cancer (NSCLC), to include extra endpoints for both the combo and monotherapy.
The Phase III MYSTIC trial was originally designed to assess the benefit of durvalumab monotherapy and a combination of durvalumab and tremelimumab (durva + treme) versus standard-of-care (SoC) chemotherapy, with a focus on progression-free survival (PFS).
The study will now assess PFS and overall survival (OS) endpoints in patients with PDL1-expressing tumours for both durvalumab monotherapy and the combination therapy, as well as in ‘all comers’ for the combination of durva + treme, versus SoC chemotherapy.
While the focus remains on exploring the benefit of the combination, AZ says it has updated the endpoints to include OS and PFS in durvalumab monotherapy following recent internal and external data showing its potential as a standalone, as well as significant opportunities in the competitive landscape. MYSTIC also includes several undisclosed interim analyses for OS.
PFS data are now expected in mid-2017 and final OS data at the latest in 2018.
The firm also noted that the ongoing Phase III NEPTUNE trial will be expanded with local patients to support regulatory submission of durva + treme combination therapy in China for 1st-line NSCLC patients, without delaying the anticipated OS data readout in 2018 from the global cohort, which is approaching full recruitment.
Additionally, it has initiated the new Phase III PEARL trial of durvalumab monotherapy versus SoC chemotherapy in 1st-line NSCLC patients whose tumours express PD-L1, with a focus on Asian countries given the high prevalence of NSCLC in the region.
“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,” noted Sean Bohen, AZ’ chief medical officer.
Durvalumab is currently undergoing a priority review in the US a potential treatment for bladder cancer, targeting patients with locally advanced or metastatic urothelial carcinoma whose disease has progressed during or after one standard platinum‑based regimen.
The PD-L1 human monoclonal antibody (mAb) is also being assessed in a range of other cancers, including head and neck, liver, and blood cancer.
Tremelimumab recently failed to show significant benefit in a mid-stage trial assessing its affect on overall survival in patients with mesothelioma, but is also being studied across a range of other tumour types in combination with durvalumab.
