Durvalumab Combination Fails to Meet Primary End Point in NSCLC Trial

In November, AstraZeneca announced that the phase 3 MYSTIC trial investigating durvalumab (Imfinzi) monotherapy and durvalumab in combination with tremelimumab in patients with previously untreated stage IV non—small cell lung cancer (NSCLC) did not meet its primary end point.

The MYSTIC trial, a phase 3, randomized, open-label, multicenter, global trial, studied monotherapy or combination durvalumab with tremelimumab versus the standard of care chemotherapy in the first-line treatment of patients with epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) wild-type, locally advanced, or metastatic NSCLC.

Primary end points included progression-free survival with the combination and overall survival with the monotherapy and combination treatment. The combination of durvalumab and tremelimumab did not meet the primary end point of improving progression-free survival compared with the current standard of care in patients whose tumors express PD-L1 on 25% or more of their cancer cells.

While the overall survival did not achieve statistical significance, a hazard ratio of 0.76 (97.54% CI, 0.564-1.019; nominal P = .036) was demonstrated with durvalumab as a monotherapy. The combination treatment displayed a hazard ratio of 0.85 (98.77% CI, 0.611-1.173; nominal P = .202). “The data support further analysis in exploratory subgroups,” read the press release.

Additionally, the safety and tolerability of durvalumab and durvalumab plus tremelimumab were consistent with what has been seen in previous trials.

Durvalumab is currently approved for unresectable stage III NSCLC in more than 40 countries, including the US, European Union, and Japan. Phase 3 trials investigating the drug for the treatment of stage IV NSCLC are ongoing.

“We are encouraged to see that Imfinzi monotherapy activity is in-line with that of the anti-PD-1 class in previously-untreated patients with stage IV [NSCLC]; however, we are disappointed that these results missed statistical significance,” said Sean Bohen, executive vice president, global medicines development and chief medical officer at AstraZeneca.

“We remain confident in Imfinzi as the cornerstone of our [immuno-oncology] program and continue to evaluate its potential in ongoing [NSCLC] trials, including Imfinzi and Imfinzi plus tremelimumab in combination with chemotherapy.”