Merck KGaA and Pfizer have failed to meet the intended endpoint in a Phase III trial of avelumab in comparison with docetaxel in patients with unresectable, recurrent or metastatic non-small cell lung cancer (NSCLC) whose disease progressed after treatment with a platinum-containing doublet therapy.

The JAVELIN Lung 200 trial’s prespecified endpoint was to improve overall survival (OS) in patients with programmed death ligand-1-positive (PD-L1+) (1% or higher) tumours.

The proportion of patients in the chemotherapy arm crossing over to immune checkpoint inhibitors outside the study was higher than previously reported in post-platinum immunotherapy clinical trials, and this could have confused the outcome of the trial, noted both companies.

However, the trial has observed improvements in OS against the control arm in the moderate-to-high PD-L1+ expression and high PD-L1+ expression population.

Avelumab’s safety profile was found to be consistent with the ones observed in the overall JAVELIN clinical development programme. The trial did not identify any new safety signals.

“Avelumab performed in line with expectations in the trial from both an efficacy and safety perspective.”

JAVELIN Lung 200 trial primary investigator Fabrice Barlesi said: “Avelumab performed in line with expectations in the trial from both an efficacy and safety perspective.

“With immune checkpoint inhibitors approved for patients with previously treated, advanced non-small cell lung cancer, higher percentages of immunotherapy-naive patients are receiving subsequent checkpoint inhibitors in their progressive treatments.

“This was observed in the JAVELIN Lung 200 control arm and may have confounded the primary outcome of the study.”

The randomised, open-label, multicenter trial JAVELIN Lung 200 enrolled 792 patients from around 260 sites in North America, South America, Asia, Africa, Australia, and Europe.

In December last year, the US Food and Drug Administration (FDA) granted its breakthrough therapy designation for avelumab as a combination therapy for treatment-naive patients with advanced renal cell carcinoma.