US regulators have granted AstraZeneca’s Imfinzi breakthrough status for the treatment of certain patients with locally-advanced, unresectable non-small cell lung cancer (NSCLC).

The designation relates to patients whose disease has not progressed following platinum-based chemoradiation therapy, highlighting its potential in a much earlier stage in the treatment pathway when the only current option is ‘active monitoring’.

“Unfortunately, for the majority of patients, their cancer will progress to metastatic disease, typically within 12 months,” noted Sean Bohen, executive vice president, Global Medicines Development and chief medical officer at AstraZeneca, and added that Imfinzi (durvalumab) “is the first immuno-oncology medicine to show a clinically-significant benefit in this earlier, non-metastatic setting.”

The breakthrough designation, which should expedite the development and regulatory review of the drug, was issued on the back of interim data from the Phase III PACIFIC trial showing statistically-significant and clinically-meaningful improvements in progression-free survival (PFS) in patients taking Imfinzi versus placebo.

The news will be particularly welcome given the high-profile failure of Imfinzi plus tremelimumab to hit PFS targets in a wider lung cancer patient population the Phase III MYSTIC trial, which is assessing the combination versus platinum-based standard-of-care chemotherapy in previously-untreated patients with metastatic (Stage IV) first-line NSCLC.

As a secondary endpoint, although not formally tested, Imfinzi monotherapy would not have met a pre-specified threshold of PFS benefit over standard of care in this disease setting, AZ said. The trial will, however, continue to assess two additional primary endpoints of overall survival for both Imfinzi monotherapy and the Imfinzi plus tremelimumab combination, with results expected in the first half of next year.

In the Stage IV first-line setting for patients with advanced NSCLC, Imfinzi as monotherapy and in combination with tremelimumab is also being tested in the NEPTUNE and PEARL Phase III trials, while the POSEIDON trial is evaluating the drug with and without tremelimumab in combination with chemotherapy. A late-stage study assessing Imfinzi in the adjuvant NSCLC setting is also ongoing.