An independent data monitoring committee stopped a major phase III clinical trial of the investigational drug everolimus (RAD001) after interim results showed significantly better progression-free survival in patients with advanced kidney cancer who received everolimus compared to placebo.

The committee stopped the trial of more than 400 patients conducted in 12 countries because the study met its primary endpoint. The interim findings are being shared with investigators to allow them to offer everolimus to patients remaining on placebo. Everolimus may fulfil an unmet medical need for patients with advanced renal cell cancer (RCC) who currently have no approved treatment options.

Everolimus is a once-daily oral therapy that offers a new approach to cancer treatment by inhibiting the mTOR protein, a central regulator of tumour cell division and blood vessel growth in cancer cells. The trial included patients who had their cancer worsen despite receiving approved treatments for RCC, such as Bayer's Nexavar (sorafenib) or Pfizer's Sutent (sunitinib) or both. In addition, prior therapy with Genentech's Avastin (bevacizumab) and interferon was allowed.

"Everolimus has the potential to greatly help patients with kidney cancer, especially in advanced stage who up to now have had no treatment options, as patients in the clinical trial on everolimus experienced a significantly longer period of time during which their cancer did not progress," said Daniel Vasella, chairman and CEO, Novartis. "Everolimus is a targeted therapy which is being studied in multiple tumour types, and could provide significant benefit to patients suffering from cancer".

"This progression-free survival benefit demonstrates the possibilities of continuous mTOR inhibition as a promising target in oncology," said David Epstein, president and CEO, Novartis Oncology. "These data are the first from a broad clinical research program that includes studies in patients with high unmet needs suffering from a variety of cancers. Everolimus is the first compound in our dynamic oncology late-stage pipeline with 6 compounds in registration trials to show exciting clinical data this year".

Complete results of the RECORD-1 (REnal Cell cancer treatment with Oral RAD001 given Daily) trial will be submitted as a late-breaking abstract for presentation at the American Society of Clinical Oncology annual meeting in May. Worldwide regulatory filings for this indication beginning with US and EU will occur in the second half of 2008.

RECORD-1 is the largest phase III trial to investigate the potential of the oral mTOR inhibitor everolimus as a treatment option for patients with metastatic RCC who have failed prior targeted therapy. The randomized, double-blind multi-centre phase III study compared everolimus to placebo.
Patients in the study were randomized according to Memorial Sloan-Kettering Cancer Centre (MSKCC) risk criteria and prior anti-cancer therapy. MSKCC risk criteria are standard clinical criteria to determine the prognosis of patients with RCC.

In addition to RCC, everolimus is presently being evaluated in neuroendocrine tumours, lymphoma, other cancers, and tuberous sclerosis as a single agent or in combination with existing cancer therapies.

Safety findings in the study were manageable and consistent with prior phase II studies. Common adverse events in the study included mouth ulcers, high blood lipids, high blood sugar, skin rash, low red blood count, low phosphate levels, and inflammation of the lungs.

Everolimus, an oral inhibitor of mTOR, is an investigational drug being studied in multiple tumour types. In cancer cells, everolimus inhibits mTOR, a protein that acts as a central regulator of tumour cell division, cell metabolism and blood vessel growth. Everolimus is a once-daily oral therapy that provides continuous inhibition of mTOR.