Merck Serono, a division of Merck, Darmstadt, Germany, announced today the strategic decision to voluntarily withdraw the marketing authorization application (MAA) to the European Medicines Agency (EMA) of a label extension for cetuximab in combination with standard 1st-line platinum-based chemotherapy in patients with advanced or metastatic non-small cell lung cancer (NSCLC) with high epidermal growth factor receptor (EGFR) expression.

The decision to withdraw the application was based on feedback from European regulatory authorities, indicating that further data would be required.

The decision does not alter the proven utility of cetuximab in its already approved indications in metastatic colorectal cancer (mCRC) and squamous cell carcinoma of the head and neck (SCCHN).

“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 cetuximab in this specific population,” said Dr. Annalisa Jenkins, Head of Global Drug Development and Medical for Merck Serono.

“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.”

Merck’s partner Threshold Pharmaceuticals, Inc. announced on that data from a randomised open-label Phase IIb clinical trial of investigational hypoxia-targeted drug TH-302 in patients with advanced pancreatic cancer will be presented at the European Society for Medical Oncology (ESMO) 2012 Congress in Vienna.

Threshold announced in February 2012 that the study met its primary endpoint demonstrating a statistically significant 63% improvement (p=0.005) in progression free survival (PFS) 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.

New findings on overall survival, which was a secondary endpoint of the study, indicate that patients treated with gemcitabine alone had a median overall survival of 6.9 months compared with 9.2 months for patients treated with 340 mg/m2 TH-302 plus gemcitabine (HR: 0.955, 95% CI: 0.67–1.37, p=0.800) and 8.7 months for patients treated with 240 mg/m2 TH-302 plus gemcitabine (HR: 0.960, 95% CI: 0.67–1.38, p=0.827).

While not statistically significant, the improvement in median overall survival is consistent with the improvement in median PFS reported previously. The trial was not designed to detect a statistically significant improvement in overall survival and included a cross-over component. Patients receiving gemcitabine alone who crossed over to receive gemcitabine plus TH-302 upon disease progression did contribute to an increase in survival of the control arm.

TH-302 continues to demonstrate a safety profile consistent with what has been previously reported at the 2012 annual meeting of the American Association of Cancer Research.

The most common adverse events were fatigue, nausea, constipation and peripheral edema, and were similar across groups. Skin and mucosal toxicities and myelosuppression were the most common adverse events related to TH-302, were mostly Grade I and II, and did not result in increases in treatment discontinuation.

Adverse events leading to discontinuation of study treatment as well as serious adverse events were balanced across all treatment arms. Grade III/IV/V adverse events were generally below 10%.

Source: Merck Serono