Exelixis, Inc. announced that its partner Ipsen received approval from the European Commission (EC) for Cabometyx (cabozantinib) 20 mg, 40 mg and 60 mg for the first-line treatment of adults with intermediate- or poor-risk advanced renal cell carcinoma (RCC) in the European Union.

“The expanded marketing authorisation of Cabometyx to include previously untreated patients in Europe with intermediate- or poor-risk advanced kidney cancer is an exciting milestone for a patient population in need of more treatment options,” said Michael M. Morrissey, Ph.D., president and chief executive officer of Exelixis. “We look forward to our continued collaboration with our partners Ipsen and Takeda to bring new options to more patients with difficult-to-treat cancers in Europe and around the world.”

Under the terms of the Collaboration and License Agreement with Ipsen, Exelixis will receive a milestone payment of $50 million for the EC approval, of which approximately $46 million was recognised as collaboration revenue in the first quarter of 2018. The payment will be made by Ipsen within the next 70 days.

Cabometyx was approved in the European Union in September 2016 for the treatment of advanced RCC in adults following prior vascular endothelial growth factor (VEGF)-targeted therapy. The expanded EC approval to include first-line treatment is based on results of the CABOSUN trial, which met its primary endpoint of improved progression-free survival (PFS) compared with sunitinib in patients with previously untreated advanced RCC determined to be intermediate- or poor-risk by the International Metastatic RCC Database Consortium (IMDC) criteria. In December 2017, theUS Food and Drug Administration (FDA) approved Cabometyx for the expanded indication of patients with advanced RCC based on the results from the CABOSUN trial.

On May 23, 2016, Exelixis announced that the phase 2 CABOSUN study met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in PFS compared with sunitinib in patients with advanced intermediate- or poor-risk RCC as determined by investigator assessment. The CABOSUN study was conducted by The Alliance for Clinical Trials in Oncology and was sponsored by the National Cancer Institute-Cancer Therapy Evaluation Program (NCI-CTEP) under the Cooperative Research and Development Agreement with Exelixis for the development of cabozantinib. These results were first presented by Dr. Toni Choueiri at the European Society for Medical Oncology (ESMO) 2016 Congress, and published in the Journal of Clinical Oncology (Choueiri, JCO, 2016). In June 2017, a blinded independent radiology review committee (IRC) confirmed that cabozantinib provided a clinically meaningful and statistically significant improvement in the primary efficacy endpoint of investigator-assessed PFS. Results from the IRC review were presented by Dr. Toni Choueiri at the ESMO 2017 Congress.

CABOSUN was a randomised, open-label, active-controlled phase 2 trial that enrolled 157 patients with advanced RCC determined to be intermediate- or poor-risk by the IMDC criteria. Patients were randomised 1:1 to receive cabozantinib (60 mg once daily) or sunitinib (50 mg once daily, 4 weeks on followed by 2 weeks off). The primary endpoint was PFS. Secondary endpoints included overall survival, objective response rate and safety. Eligible patients were required to have locally advanced or metastatic clear-cell RCC, ECOG performance status 0-2 and had to be intermediate- or poor-risk per the IMDC criteria (Heng, JCO, 2009).2 Prior systemic treatment for RCC was not permitted.

The American Cancer Society’s 2018 statistics cite kidney cancer as among the top ten most commonly diagnosed forms of cancer among both men and women in theUS Clear cell RCC is the most common type of kidney cancer in adults. If detected in its early stages, the five-year survival rate for RCC is high; for patients with advanced or late-stage metastatic RCC, however, the five-year survival rate is only 12 per cent, with no identified cure for the disease. Approximately 30,000 patients in theUS and 68,000 globally require treatment, and an estimated 14,000 patients in theUS each year are in need of a first-line treatment for advanced kidney cancer.