- As the race to market for immuno-oncology drugs in first-line lung cancer continues apace, AstraZeneca has moved to boost the data from its Phase 3 MYSTIC trial by changing the focus of the endpoints and strengthening the statistical analysis.
- The changes will shift the timeline of the study, with progression-free survival (PFS) data expected in mid-2107 and final overall survival (OS) data by 2018.
- The sudy will now assess PFS and OS in patients with PDL1-expressing tumors who are treated with either durvalumab monotherapy or a combination of druvalumab and tremelimumab, as well as in "all comers" treated with the combo, compared to standard of care.
Just over a year ago, after the results from the ATLANTIC study didn't appear strong enough to support durvalumab as a monotherapy candidate for fast track designation, AstraZeneca shifted the drug's focus to combination therapy.
Now, however, AstraZeneca is widening the focus of the Phase 3 MYSTIC trial to focus on the monotherapy and PD-L1 expressors based on recent monotherapy data and on the opportunity for PDL1-targeting drugs in non-small cell lung cancer (NSCLC). The changes will increase the recruitment and elevate OS to a primary endpoint.
The NSCLC market is growing rapidly, and could be worth as much as $26.7 billion across the eight major markets by 2025, according to GlobalData. Companies developing checkpoint inhibitors are fighting for their share of it, particularly in the first-line setting. Bristol-Myers Squibb's Opdivo (nivolumab) has a broad chunk of the second-line market but its failure in the CheckMate-026 first-line study has opened the door for rival Merck & Co. to make up ground.
Merck's Keytruda (pembrolizumab) has already been approved for first-line use in selected NSCLC, making it the first checkpoint inhibitor approved for untreated lung cancer.
Analysts at Jefferies see the news from AstraZeneca as positive for the British pharma and negative for Merck.
"OS has been given increased significance in the durva mono arm of the study, which we assume has been done to increase the probability of success at lower levels of PD-L1 expression than Merck & Co. achieved in KN-024," wrote Jefferies analyst Jeffrey Holford in a note to investors.
Analysts expect the company to file the combination in PD-L1 expressors in the second half of 2017, and for a monotherapy in the same patient group in the first half of 2018. A readout of PFS data, originally expected in early 2017, will be pushed back to mid-2017.
AstraZeneca is also expanding the Phase 3 NEPTUNE trial in China, potentially allowing Chinese approval submission for the combination in first-line NSCLC to go ahead without delays caused by the MYSTIC global study changes. Also in Asia, another Phase 2 trial, PEARL, will look at durvalumab monotherapy against standard of care in first-line 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," said Sean Bohen, chief medical officer at AstraZeneca.
It hasn't always been plain sailing for durvalumab. Two studies for the drug in head and neck squamous cell carcinoma (HNSCC) were halted in October 2016 because of bleeding. The hold was only temporary, however, and the studies restarted in November 2016 without any amendments.