Exelixis announces submission of sNDA to FDA for CABOMETYX plus Opdivo for advanced RCC

“We are excited to complete our first regulatory submission for CABOMETYX in combination with an immune-checkpoint inhibitor based on the positive results from the CheckMate -9ER phase 3 pivotal trial, which showed a statistically significant and clinically meaningful benefit in the key efficacy measures of progression-free survival, overall survival and objective response rate for patients with previously untreated kidney cancer,” said Gisela Schwab, M.D., President, Product Development and Medical Affairs and Chief Medical Officer, Exelixis.

“We expect that, if approved, the combination of CABOMETYX and Opdivo will be an important new first-line treatment regimen for RCC patients who need additional therapeutic options that extend survival. We look forward to continuing to work closely with Bristol Myers Squibb and the FDA through the regulatory review process.”

The sNDA is based on the results of CheckMate -9ER, a phase 3 pivotal trial evaluating CABOMETYX in combination with Opdivo compared with sunitinib in previously untreated patients with advanced or metastatic RCC. Exelixis and Bristol Myers Squibb announced in April 2020 that the trial met its primary endpoint of significantly improving progression-free survival (PFS) at final analysis, as well as the secondary endpoints of overall survival (OS) at a pre-specified interim analysis, and objective response rate (ORR). Preliminary assessment showed a favorable safety profile, with a low frequency of treatment discontinuations due to adverse events.

The detailed results of CheckMate -9ER will be presented during the upcoming European Society of Medical Oncology (ESMO) Virtual Congress 2020, during Presidential Symposium II on September 20, 2020.

CheckMate -9ER is an open-label, randomized, multi-national phase 3 trial evaluating patients with previously untreated advanced or metastatic renal cell carcinoma. Patients were randomized 1:1 to Opdivo and CABOMETYX or sunitinib. The primary endpoint is PFS. Secondary endpoints include OS and ORR. The primary efficacy analysis compares the doublet combination of cabozantinib and nivolumab versus sunitinib in all randomized patients. The trial is sponsored by Bristol Myers Squibb and Ono Pharmaceutical Co and co-funded by Exelixis, Ipsen and Takeda Pharmaceutical Company Limited.

The American Cancer Society’s 2020 statistics cite kidney cancer as among the top ten most commonly diagnosed forms of cancer among both men and women in the U.S.¹ Clear cell RCC is the most common type of kidney cancer in adults.² 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%.² Approximately 32,000 patients in the U.S. and 71,000 worldwide will require systemic treatment for advanced kidney cancer in 2020.³

About 70% of RCC cases are known as “clear cell” carcinomas, based on histology.⁴ The majority of clear cell RCC tumors have below-normal levels of a protein called von Hippel-Lindau, which leads to higher levels of MET, AXL and VEGF.^5,6 These proteins promote tumor angiogenesis (blood vessel growth), growth, invasiveness and metastasis.^7,8,9,10 MET and AXL may provide escape pathways that drive resistance to VEGF receptor inhibitors.^6,7

In the U.S., CABOMETYX tablets are approved for the treatment of patients with advanced RCC and for the treatment of patients with HCC who have been previously treated with sorafenib. CABOMETYX tablets have also received regulatory approvals in the European Union and additional countries and regions worldwide. In 2016, Exelixis granted Ipsen exclusive rights for the commercialization and further clinical development of cabozantinib outside of the United States and Japan.

In 2017, Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited for the commercialization and further clinical development of cabozantinib for all future indications in Japan. Exelixis holds the exclusive rights to develop and commercialize cabozantinib in the United States.

Source: Company Press Release