AstraZeneca plc (LSE:AZN; NYSE:AZN) said Imfinzi durvalumab plus tremelimumab as third-line treatment missed the primary endpoints in non-small cell lung cancer patients with low or negative PD-L1 expression in the Phase III ARCTIC trial.
The trial consisted of two substudies in about 597 patients with locally advanced or metastatic NSCLC who had received at least two prior treatments. Substudy A enrolled patients with high PD-L1 expression, defined as ≥25% of tumor cells with membrane staining, to receive standard of care (SOC) chemotherapy or Imfinzi monotherapy. Substudy B enrolled patients with low or negative PD-L1 expression to receive SOC, Imfinzi monotherapy, tremelimumab monotherapy or Imfinzi plus tremelimumab.
In patients with low or negative PD-L1 expression, Imfinzi plus CTLA-4 inhibitor tremelimumab failed to significantly improve progression-free survival (PFS) and overall survival (OS) vs. SOC.
In patients with high PD-L1 expression, AZ said Imfinzi monotherapy showed a "clinically meaningful" reduction in the risk of death compared with SOC. Substudy A was not powered for statistical significance.
Full ARCTIC data will be presented at upcoming medical meeting.
In February, FDA approved Imfinzi to treat unresectable stage III NSCLC that has not progressed following concurrent platinum-based chemotherapy and radiation. The human IgG1 mAb targeting PD-L1 also has accelerated approval from FDA for the second-line treatment of locally advanced or metastatic urothelial carcinoma (see BioCentury Extra, Feb. 16).
In July 2017, AZ lost $12.8 billion in market cap after it said first-line treatment with Imfinzi plus tremelimumab missed the co-primary endpoint of improving PFS in the Phase III MYSTIC trial to treat stage IV NSCLC. AZ expects a final analysis next half of MYSTIC's co-primary OS endpoint (see BioCentury Extra, July 27, 2017).