AstraZeneca (AZ) has set new targets in a pivotal trial of its immuno-oncology drugs durvalumab and tremelimumab in lung cancer that it hopes will give it an edge over its rivals.
The UK drugmaker is setting tougher objectives in the MYSTIC trial – including adding overall survival as a primary endpoint along with progression-free survival (PFS) – as it strives to position the drug against Merck & Co’s Keytruda (pembrolizumab) and other competitors in the cancer immunotherapy sector.
MYSTIC is testing PD-L1 inhibitor durvalumab as a monotherapy and in combination with CTLA-4 inhibitor tremelimumab as a first-line therapy for non-small cell lung cancer (NSCLC), comparing the two regimens with standard chemotherapy. The new protocol will investigate durvalumab monotherapy in patients with PD-L1-positive tumours, while the combination will be used in “all-comers”, regardless of their PD-L1 status.
Previously, AZ has said the combination is its main focus so the elevation of the monotherapy arm marks a change in direction for the firm, and according to analysts could be a move designed to make it easier for clinicians to include durvalumab in other combination regimens. AZ also announced it was starting a new phase III trial called PEARL that will pit durvalumab monotherapy against chemotherapy in Asia.
The company said the move was 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”.
The tougher survival endpoints also pitch both arms of the study against PD-1 inhibitor Keytruda, which was approved for first-line NSCLC on the back of PFS data but included overall survival among the secondary endpoints of its pivotal KEYNOTE-024 trial. Since then, Merck has also filed for an FDA green light for Keytruda in combination with chemotherapy in this setting.
Merck’s longstanding rival Bristol-Myers Squibb failed to make headway in first-line NSCLC after its Opdivo (nivolumab) PD-1 inhibitor failed to show a benefit in a phase III trial reported last year. Meanwhile, third PD-1/PD-L1 inhibitor entrant Roche’s Tecentriq (atezolizumab) has been approved for second-line NSCLC and is in phase III trials ongoing as a first-line monotherapy as well as in combination with other drugs.
AZ’s chief medical officer Sean Bohen said the changes to the trial programme “are all designed to enhance our options in first-line NSCLC” for cancer immunotherapy combinations as well as monotherapy, adding that the first data should be available in mid-2017.