Biotech Values

[DewDiligence]

AZN -3% on MYSTIC-study OS failure in mono and combo arms:

https://www.astrazeneca.com/media-centre/press-releases/2018/astrazeneca-provides-update-on-the-phase-iii-mystic-trial-of-imfinzi-and-tremelimumab-in-stage-iv-non-small-cell-lung-cancer16112018.html

AstraZeneca…today announced final overall survival (OS) results for the Phase III MYSTIC trial, a randomised, open-label, multi-centre, global trial of Imfinzi (durvalumab) monotherapy and the combination of Imfinzi and tremelimumab, an anti-CTLA4 antibody, versus standard-of-care (SoC) platinum-based chemotherapy in previously-untreated patients with Stage IV (metastatic) non-small cell lung cancer (NSCLC).

In the primary analysis population of patients, whose tumours express PD-L1 on 25% or more of their cancer cells as determined by the VENTANA PD-L1 (SP263) Assay, Imfinzi monotherapy and the combination of Imfinzi plus tremelimumab did not meet the primary endpoints of improving OS compared to SoC chemotherapy. While the OS result did not meet statistical significance, a hazard ratio (HR) of 0.76 (97.54% CI 0.564-1.019; nominal p=0.036) was observed with Imfinzi monotherapy. The combination therapy had an HR of 0.85 (98.77% CI 0.611-1.173; nominal p=0.202); the data support further analysis in exploratory subgroups.

The p-value of 0.036 for Imfinzi monotherapy was deemed non-statsig because the MYSTIC study’s alpha was divided into so many components (mono and combo therapy for PFS, and mono and combo therapy for OS). AZN reported failure of both arms on the PFS endpoint in 2017 (#msg-133336714).

A quirk of the OS data is that Imfinzi plus Tremelimumab performed numerically worse than Imfinzi monotherapy.

Imfinzi continues to be tested in other phase-3 trials in first-line Stage-IV NSCLC; to date, however, Imfinzi has succeeded only in second-line bladder cancer (#msg-130966037) and second line Stage-III NSCLC (#msg-138626896).