Merck KGaA withdraws Erbitux NSCLC filing
This article was originally published in Scrip
Merck KGaA has decided to voluntarily withdraw its marketing authorisation application (MAA) to the European Medicines Agency (EMA) for a label extension for Erbitux (cetuximab) in non-small cell lung cancer (NSCLC).
The MAA was for Erbitux in combination with standard first-line platinum-based chemotherapy in patients with advanced or metastatic non-small cell lung cancer (NSCLC) with high epidermal growth factor receptor (EGFR) expression. It is already approved to treat metastatic colorectal cancer and head and neck cancer.
Merck licensed the right to market Erbitux outside the US and Canada from ImClone, now a subsidiary of Lilly, in 1998.
In April, Lilly and its US partner Bristol-Myers Squibb received a complete response letter from the US FDA on their filing for Erbitux in the first-line NSCLC indication. The companies said they had no plans to resubmit the filing (scripintelligence.com, 27 April 2012).
This was Merck's second recent disappointment with Erbitux. In July it said that the Phase III EXPAND trial assessing Erbitux in combination with cisplatin and capecitabine as a first-line treatment for patients with advanced gastric adenocarcinoma including adenocarcinoma of the gastro-oesophageal junction did not meet its primary endpoint of improving progression free survival.
"We are disappointed that we have not been able to move forward with the filing in NSCLC but it has become apparent that further data will be required to support the clinical utility of Erbitux in this specific population," said Dr Annalisa Jenkins, head of global drug development and medical for the Merck Serono division. "We continue to advance our oncology pipeline, for example also by planning to initiate a randomised Phase III trial of TH-302 in patients with advanced first-line pancreatic cancer together with our partner Threshold [Pharmaceuticals]."
Threshold's share price took a battering yesterday when it reported that the tumour hypoxia-targeting small molecule TH-302 did not show a significant improvement in overall survival, a secondary endpoint, in a Phase IIb trial in pancreatic cancer patients (scripintelligence.com, 18 September 2012). The company said the data nevertheless supported Phase III development.
Threshold announced in February that the study met its primary endpoint, demonstrating a statistically significant 63% improvement (p=0.005) in progression free survival for patients treated with TH-302 and gemcitabine versus gemcitabine alone. This represented a 2-month increase in PFS for patients treated with TH-302.
TH-302 is already being evaluated in a Phase III advanced soft tissue sarcoma study in which the drug is administered in combination with doxorubicin. An independent data monitoring committee will do a futility analysis during the first half of next year and patient enrolment is expected to be complete around the end of 2013.
It is also being investigated in haematological malignancies and in combination trials in solid tumours in Phase I.