MYSTIC Trial Yields Disappointing Results for AstraZeneca's Durvalumab Combination in NSCLC

AstraZeneca announced that its immuno-oncology drug durvalumab, in combination with tremelimumab, failed to meet progression-free survival (PFS) endpoint in the MYSTIC trial of patients with metastatic non-small cell lung cancer (NSCLC).

A press release from the drug manufacturer stated that the combination of durvalumab (Imfinzi) and tremelimumab did not meet the primary endpoint of improved PFS compared with standard-of-care chemotherapy in previously-untreated patients with stage IV NSCLC whose tumors express programmed death ligand-1 (PD-L1) on at least 25% of their cancer cells.

PFS with durvalumab alone was a secondary endpoint and thus not formally analyzed, but the statement indicated that durvalumab monotherapy also failed to demonstrate superiority over chemotherapy in this NSCLC patient population.

Durvalumab, which is a monoclonal antibody that attacks PD-L1, is being studied alone and in combination in trials like MYSTIC, which is evaluating its use in treating NSCLC. Other ongoing phase 3 trials are testing durvalumab in small-cell lung cancer (SCLC), head and neck squamous cell carcinoma (HNSCC), and metastatic urothelial carcinoma (mUC). It recently received accelerated approval from the FDA for use in previously-treated patients with mUC.

The rationale behind combining durvalumab with tremelimumab is that the latter monoclonal antibody will target cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). By blocking CTLA-4, tremelimumab can help activate T cells and boost the immune response to cancer triggered by the PD-L1—blocking durvalumab. Phase 3 trials are currently testing this combination in mUC, NSCLC, SCLC, and HNSCC, while phase 1/2 trials are being conducted for hepatocellular carcinoma and hematological malignancies.

This robust trial portfolio will persist despite the lackluster PFS results in NSCLC, AstraZeneca declared. The MYSTIC trial will continue to assess overall survival for durvalumab alone and with tremelimumab, and final data should be complete by the first half of 2016. A strength of this phase III trial is that it is being conducted across 167 cancer centers in 17 countries.

“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 and we look forward to evaluating the remaining primary endpoints of overall survival for both mono- and combination therapy,” said Sean Bohen, AstraZeneca’s chief medical officer and executive vice president of Global Medicines Development, in the press statement.