AstraZeneca’s share price took a 16% dive by mid-morning as the firm announced that its key anticancer monoclonal antibody (mAb) Imfinzi™ (durvalumab) failed to meet an initial primary progression-free survival (PFS) endpoint in a late-stage study in advanced lung cancer. News of the MYSTIC trial’s disappointing early results overshadowed positive data reported in parallel from a separate late-stage trial with the firm’s established epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor Tagrisso® (osimertinib) and the announcement of a potentially $8.5 billion cancer drug development deal with Merck & Co.

The open-label Phase III MYSTIC study is evaluating AstraZeneca’s anti-programmed death-ligand 1 (PD-L1) inhibitor Imfinzi both as monotherapy and in combination with the firm’s investigational cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) monoclonal antibody (mAb) tremelimumab in patients with previously untreated metastatic (Stage IV) first-line non-small-cell lung cancer (NSCLC). The study data released today showed that combined treatment didn’t improve PFS when compared with platinum-based standard-of-care (SoC) in patients whose tumors express PD-L1 on at least 25% of their cancer cells. A secondary endpoint wasn’t formally tested, but indicated that Imfinzi monotherapy also would not have met a prespecified PFS benefit in comparison with SoC. Data on the main primary endpoints of overall survival for both the monotherapy and combination therapy arms are expected during H1 2018. 

Sean Bohen, M.D., Ph.D., evp for Global Medicines Development and CMO at AstraZeneca admitted the PFS survival data were “disappointing,” but pointed out that the study was designed to assess overall survival.

Imfinzi won its first accelerated FDA approval in May as therapy for previously treated patients with locally advanced or metastatic urothelial carcinoma (mUC).

The separately reported Phase III FLAURA study showed that Tagrisso monotherapy led to statistically significant and clinically meaningful improvements in PFS compared with current first-line SoC using erlotinib or gefitinib in previously untreated patients with locally advanced or metastatic EGFR mutation-positive NSCLC. Tagrisso is already approved in more than 50 countries, including the U.S., EU, Japan, and China, for therapy in previously treated patients with EGFR T790M mutation-positive advanced NSCLC. The FDA converted its accelerated Tagrisso approval for the NSCLC indication to regular approval back in March.

Tagrisso is separately being investigated in adjuvant and metastatic first-line settings, including in patients with and without central nervous system metastases, in leptomeningeal metastases, and in combination with other treatments.

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