AZ’s MYSTIC survival data is in – and it’s a bust

AstraZeneca has released the overall survival (OS) data from its MYSTIC trial of Imfinzi and tremelimumab in advanced non-small cell lung cancer (NSCLC), and it has confirmed the study is a failure.

There was no OS improvement for PD-L1 inhibitor Imfinzi (durvalumab) either alone or in combination with AZ’s experimental CTLA4 inhibitor tremelimumab in previously-untreated stage IV NSCLC patients with higher levels of PD-L1 expression in their tumours (25% or more). The read-out matches the disappointing progression-free survival (PFS) data reported last year.

Trying to draw some good news from the data, AZ pointed to a 24% reduction in the risk of death for Imfinzi given on its own compared to chemotherapy, but prospects for tremelimumab look very shaky after the combination actually performed worse than Imfinzi alone.

AZ says it can see a glimmer of activity in the hazard ration (HR) data for the combination that “support further analysis in exploratory subgroups,” but that looks pretty speculative. In the meantime, AZ also has trials of Imfinzi with and without tremelimumab running in first- and second-line head and neck cancer, small cell lung cancer (SCLC) and bladder cancer.

There’s no doubt that overall the study is a big disappointment, and will allow Merck & Co’s rival PD-1 inhibitor Keytruda (pembrolizumab) to maintain its fierce grip on the first-line NSCLC market – at least for the time being. The data isn’t a terminal blow for AZ’s immuno-oncology ambitions, however, as Imfinzi has managed to carve out a niche for itself in earlier-stage, inoperable NSCLC that is starting to pay off in increased sales.

“We are encouraged to see that Imfinzi monotherapy activity is in-line with that of the anti-PD-1 class in previously-untreated patients with Stage IV NSCLC,” said AZ’s chief medical officer Sean Bohen.

“We remain confident in Imfinzi as the cornerstone of our IO programme and continue to evaluate its potential in ongoing NSCLC, including Imfinzi and Imfinzi plus tremelimumab in combination with chemotherapy,” he added.

Shares in AZ were down nearly 3% in mid-morning trading on the news.