AstraZeneca suffers setback as MYSTIC study of Imfinzi, tremelimumab fails to significantly improve survival in lung cancer

AstraZeneca announced Friday that in the Phase III MYSTIC study, the PD-L1 inhibitor Imfinzi (durvalumab) as monotherapy and in combination with the anti-CTLA4 antibody tremelimumab in previously-untreated patients with Stage IV non-small-cell lung cancer (NSCLC) failed to significantly improve overall survival (OS) versus standard-of-care platinum-based chemotherapy. Chief medical officer Sean Bohen said "we are disappointed that these results missed statistical significance."

Last year, AstraZeneca announced initial results from the MYSTIC study, with the combination of Imfinzi and tremelimumab failing to improve progression-free survival (PFS). Meanwhile, earlier this year, the company indicated that the final analysis of OS from the trial would be delayed from the first half to the second half of 2018.

The study randomised patients with EGFR and ALK wild-type, locally-advanced or metastatic NSCLC to receive Imfinzi monotherapy, Imfinzi in combination with tremelimumab, or standard-of-care chemotherapy as a first-line treatment. The trial's primary endpoints included PFS for the combination of Imfinzi and tremelimumab, and OS in monotherapy and in combination therapy.

AstraZeneca noted on Friday that the primary analysis population consisted of patients whose tumours express PD-L1 on 25 percent or more of their cancer cells. The drugmaker said that while the OS result did not meet statistical significance, a hazard ratio (HR) of 0.76 was observed with Imfinzi monotherapy, while the HR for the combination therapy was 0.85. AstraZeneca suggested that the data "support further analysis in exploratory subgroups."

"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 non-small cell lung cancer," Bohen remarked. The company noted that the safety and tolerability profiles for Imfinzi and the Imfinzi plus tremelimumab combination in the MYSTIC study were consistent with previous trials.

Imfinzi is approved for unresectable, Stage III NSCLC in more than 40 countries, including the US, EU and Japan, based on the late-stage PACIFIC trial. The drug is also being tested in a range of Phase III studies for Stage IV NSCLC, including the PEARL, NEPTUNE and POSEIDON trials.

Earlier this month, AstraZeneca reported that third-quarter sales of Imfinzi reached $187 million, coming in above estimates, with growth boosted by ongoing launches for the treatment of unresectable, Stage III NSCLC.

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