Treatment with Imfinzi (durvalumab), with or without the investigational immunotherapy tremelimumab, failed to extend the survival of patients with metastatic non-small cell lung cancer (NSCLC) compared with standard chemotherapy in a Phase 3 trial, according to AstraZeneca and its subsidiary, MedImmune.

The open-label MYSTIC trial (NCT02453282) compared the different approaches as a first-line treatment for patients without mutations in the epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) proteins, two well-characterized molecular targets in NSCLC.

MYSTIC was conducted at 167 centers across 17 countries. Besides overall survival, the trial’s other primary objective was to assess if Imfinzi, alone or in combination with tremelimumab, extended the time patients lived without disease worsening.

Imfinzi is a human antibody that binds to the PD-L1 protein found on the surface of cancer cells and blocks its interaction with two molecules, PD-1 and CD80, preventing the tumor’s evasion from immune attack.

The immune checkpoint inhibitor tremelimumab is an anti-CTLA4 antibody that helps to activate cancer-fighting immune T-cells.

In July 2017, results from MYSTIC had already shown that the combination did not extend the time patients lived without their disease progressing. This analysis was conducted in patients whose tumors had 25% or more cells producing the PD-L1 factor — a biomarker of response to Imfinzi — as determined by Roche‘s VENTANA PD-L1 (SP263) Assay.

Now final survival results in this patient population reveal that Imfinzi alone or in combination with tremelimumab did not significantly extend overall survival compared with standard-of-care platinum-based chemotherapy. However, the therapy alone showed a trend toward a better survival rate, supporting further subgroup analysis, according to the team.

Safety and tolerability results for Imfinzi alone or with tremelimumab were consistent with previous trials.

“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 [metastatic] non-small cell lung cancer; however, we are disappointed that these results missed statistical significance,” Sean Bohen, AstraZeneca’s executive vice president, global medicines development and chief medical officer, said in a press release.

According to Bohen, AstraZeneca remains “confident in Imfinzi as the cornerstone” of its immuno-oncology programme and will continue evaluating its potential in ongoing NSCLC trials, “including Imfinzi and Imfinzi plus tremelimumab in combination with chemotherapy.”

Besides MYSTIC, current multicenter Phase 3 studies of metastatic NSCLC include NEPTUNE (NCT02542293), PEARL (NCT03003962), and POSEIDON (NCT03164616). Both the PEARL and the POSEIDON trials are currently recruiting adults. More information on study locations and contacts are available on the trials’ webpages.

Imfinzi is approved for inoperable Stage 3 NSCLC — generally indicating cancers that have spread into nearby tissue — in more than 40 countries, including the U.S., EU, and Japan, based on progression-free survival results from the Phase 3 PACIFIC trial (NCT02125461).

In February, Imfinzi became the first immunotherapy approved for advanced NSCLC in the U.S., indicated for patients who are unable to undergo surgery and whose disease has not progressed after platinum-based chemotherapy and radiation therapy.

It is also being evaluated as a stand-alone or combination therapy with tremelimumab in small-cell lung cancer, bladder cancer, head and neck cancer, and other solid tumors.