Merck KGaA, Pfizer's Lung Cancer Drug Flunks Late-Stage Trial
Germany-based Merck KGaA and U.S.-based Pfizer announced mixed results from its Phase III JAVELIN Lung 200 clinical trial comparing avelumab to docetaxel in a subpopulation of lung cancer patients.
The study compared Bavencio (avelumab), a PD-L1 antibody, against Taxotere (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 trial didn’t meet the primary endpoint of improved overall survival (OS) in patients with PD-L1+ tumors. The companies, however, indicate that there may have been some events in the trial that “confounded this trial outcome,” namely that the proportion of patients in the chemotherapy arm that crossed over to immune checkpoint inhibitors outside the study was higher than previously reported.
What is meant by crossover is that some of those patients were allowed to switch to a rival immunotherapy when their disease worsened. With a higher percentage of patients doing so, it complicated the actual data analysis for Bavencio.
Bavencio is currently approved in two smaller cancer types, but it is competing against Merck & Co’s Keytruda (not Merck KGaA), Bristol-Myers Squibb’s Opdivo, Roche’s Tecentriq and AstraZeneca’s Imfinzi. It is approved in the U.S. for Merckel cell carcinoma (mMCC) and for previously treated patients with locally advanced or metastatic urothelial carcinoma (mUC). It is also approved for mMCC in Europe. However, it failed a Phase III trial for gastric cancer in late 2017.
Reuters notes, “Separately, Merck and Pfizer are testing Bavencio in newly-diagnosed lung cancer patients that have no prior treatment, seen as the bigger market opportunity, but results are not expected before the European summer of 2019.”
“We are confident of the role of Bavencio to play in the lung cancer market,” said Luciano Rossetti, the head of research and development at Merck’s pharmaceuticals division, Reuters reported.
The companies reported that OS improvements compared to the control arm were seen in the moderate-to-high PD-L1+ group, which means about 50% expression. And OS in the PD-L1+ group with high expression, which means over 80 percent expression, also showed improvements.
“Avelumab performed in line with expectations in the trial from both an efficacy and safety perspective,” said Fabrice Barlesi, head of multidisciplinary Oncology and Therapeutic Innovations Department at Aix-Marseille University and the Assistance Publique Hopitaux de Marseille, France, lead investigator of the study, in a statement. “With immune checkpoint inhibitors approved for patients with previously treated, advanced non-small cell lung cancer, higher percentages of immunotherapy-naïve 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.”
Remaining optimistic, Rossetti thinks the drug still has blockbuster potential, saying that the results from another trial, Javelin Lung 100, are more important. That trial is investigating avelumab as a first-line therapy in NSCLC, and results are expected in mid-2019.
Data from the trial will be presented at a future meeting. The drug is being evaluated in at least 30 clinical trials in 7,000 patients across more than 15 different types of cancers. They include breast, gastric/gastro-esophageal junction, head and neck, Hodgkin’s lymphoma, melanoma, mesothelioma, Merkel cell carcinoma, ovarian, renal cell carcinoma and urothelial carcinoma.