MYSTIC trial in stage IV lung cancer: Durvalumab plus Tremelimumab combination did not meet a primary endpoint of progression-free survival compared to chemotherapy
Progression-free survival ( PFS ) results for the phase III MYSTIC trial, a randomised, open-label, multi-centre, global trial of Durvalumab ( Imfinzi ) monotherapy or Durvalumab in combination with Tremelimumab versus Platinum-based standard-of-care chemotherapy in previously-untreated patients with metastatic ( stage IV ) 1st-line non-small cell lung cancer ( NSCLC ) were announced.
The combination of Durvalumab and Tremelimumab did not meet the primary endpoint of improving progression-free survival compared to standard-of-care in patients whose tumours express PD-L1 on 25% or more of their cancer cells ( as determined by the VENTANA PD-L1 [ SP263 ] assay ).
As a secondary endpoint, although not formally tested, Durvalumab monotherapy would not have met a pre-specified threshold of PFS benefit over standard-of-care in this disease setting.
The trial will continue to assess two additional primary endpoints of overall survival ( OS ) for Durvalumab monotherapy and overall survival for the Durvalumab plus Tremelimumab combination.
Final overall survival data from both primary endpoints are expected during the first half of 2018.
While the results from the MYSTIC trial for progression-free survival in first-line stage IV non-small cell lung cancer compared with standard of care are disappointing, the trial was designed to assess overall survival.
The MYSTIC trial is a randomised, open-label, multi-centre, global phase III trial of Durvalumab monotherapy or Durvalumab in combination with Tremelimumab versus standard-of-care in treatment of patients with epidermal growth factor receptor ( EGFR ) and anaplastic lymphoma kinase ( ALK ) wild-type locally-advanced or metastatic ( stage IV ) 1st-line NSCLC.
Primary endpoints include progression-free survival and overall survival.
Durvalumab, a human monoclonal antibody directed against PD-L1, blocks PD-L1 interaction with PD-1 and CD80 on T cells, countering the tumour's immune-evading tactics and inducing an immune response.
Tremelimumab is an investigational human monoclonal antibody that targets the activity of cytotoxic T-lymphocyte-associated protein 4 ( CTLA-4 ). Tremelimumab blocks the activity of CTLA-4, contributing to T cell activation and boosting the immune response to cancer. ( Xagena )
Source: AstraZeneca, 2017