- Investors in AstraZeneca plc will have to wait a little longer for overall survival data from a key study testing the British pharma's cancer immunotherapy Imfinzi together with the company's experimental CTLA-4 inhibitor tremelimumab in lung cancer.
- The drugmaker now expects to read out survival results from the trial, called MYSTIC, sometime in the latter half of this year, a delay from the previous estimate of June or earlier.
- Last year, MYSTIC missed its initial study objective, after first-line treatment with the immunotherapy combination failed to extend progression-free survival over standard chemotherapy. The setback badly dented AstraZeneca's hopes of quickly catching its immuno-oncology rivals in the metastatic lung cancer market.
Imfinzi (durvalumab), first approved for bladder cancer last May, is the main vehicle of AstraZeneca's ambitions to become a player in the lucrative immuno-oncology market.
The British pharma had positioned the MYSTIC study to give it a leg up in the race to find effective combination treatments that build on the success of checkpoint inhibitors in treating metastatic lung cancer.
Yet results AstraZeneca disclosed last July showed combining Imfinzi with its experimental tremelimumab offered no benefit on progression-free survival (PFS) versus platinum-based chemotherapy when given as a first-line treatment. In a further disappointment, Imfinzi monotherapy also failed to improve on standard-of-care, casting further doubt on the potential role of Imfinzi in lung cancer.
AstraZeneca has held out hope that data on overall survival (OS), a co-primary endpoint in MYSTIC, will prove the efficacy of pairing Imfinzi with tremelimumab.
PFS is an example of what's known as a surrogate endpoint — testing whether a drug can lengthen the period of time without a patient's cancer growing or further metastasizing. OS, on the other hand, measures whether treatment actually helps patients live longer and therefore is a more clinically meaningful metric.
"We ... consider overall survival not only a more meaningful endpoint for patients but actually the endpoint that better captures the benefit of I/O treatments," said Sean Bohen, AstraZeneca's chief medical officer, on a recent earnings call with investors. "We're cautiously optimistic about the MYSTIC trial, for monotherapy in high expressers and then also the hypothesis we make out with the combination."
There are some signs from studies of other immuno-oncology agents that initial PFS data may not represent the eventual benefit of treatment with checkpoint inhibitors. A trial of Bristol-Myers Squibb Company's Opdivo (nivolumab) and Yervoy (ipilimumab) in kidney cancer, for example, failed to improve PFS in a first reading of the data, only to later show a survival benefit.
AstraZeneca designed MYSTIC as an "event-driven" study, meaning analysis of overall survival is only triggered after a certain number of events — in this case deaths — occur. The previous expectation of a readout in the first half of the year was based on the company's projections of how fast those events would happen.
The delay in a readout will likely push back AstraZeneca's anticipated filing date for approval, previously pegged for sometime in the second half of the year presuming the OS data came back positive.
Since MYSTIC's setback last summer, AstraZeneca has won an approval for Imfinzi in an earlier lung cancer setting based on results from a study called PACIFIC. That success has lessened some of the sting from the MYSTIC miss and bolstered projections of the drug's future revenues.
Sales of Imfinzi reached $18 million in the fourth quarter of 2017, AstraZeneca reported in February. Those numbers, however, don't reflect the approval in Stage 3 unresectable lung cancer.