The approval is based on results from the CheckMate -9ER phase 3 pivotal trial that evaluated the CABOMETYX and OPDIVO combination compared with sunitinib in previously untreated advanced or metastatic RCC. The results were presented during the European Society of Medical Oncology Virtual Congress 2020 in September.

The FDA reviewed the application for CABOMETYX and OPDIVO under the Real-Time Oncology Review (RTOR) pilot program and Fast Track designation. The RTOR pilot program, which allows an applicant to pre-submit components of the application to allow the FDA to review clinical trial data before the complete filing is submitted, aims to explore a more efficient review process to ensure safe and effective treatments are available to patients sooner.

The CheckMate -9ER Trial Results of the Cabometyx and Opdivo Combination:

• Significant improvement of overall survival (OS) compared with sunitinib.
• Median OS has not yet been reached in either treatment arm.
• Median progression-free survival (PFS) doubled at 16.6 months compared with 8.3 months for sunitinib.
• The objective response rate (ORR) was also doubled: 56% with CABOMETYX in combination with OPDIVO and 27% with sunitinib.
• Consistent results for PFS were observed across subgroups of International Metastatic RCC Database Consortium risk status and PD-L1 tumor expression with CABOMETYX in combination with OPDIVO.
• CABOMETYX in combination with OPDIVO was generally well tolerated and reflected the known safety profiles of the tyrosine kinase inhibitor and immunotherapy components in previously untreated advanced RCC.
• The most common adverse reactions reported in at least 20% of patients treated with CABOMETYX in combination with OPDIVO were diarrhea, fatigue, hepatotoxicity, palmar-plantar erythrodysesthesia, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, decreased appetite, nausea, dysgeusia, abdominal pain, cough, and upper respiratory tract infection.
• The discontinuation rate due to all causality adverse events in the CABOMETYX in combination with OPDIVO arm was 20% for either CABOMETYX or OPDIVO (8% for CABOMETYX only, 7% for OPDIVO only and 6% for both CABOMETYX and OPDIVO due to the same adverse event at the same time).

Bryan Lewis, President, and Co-founder of KidneyCAN, said, “While significant progress has been made in the treatment landscape for advanced kidney cancer over the last several years, patients still need more therapeutic options to treat this disease as we search for a possible cure. As patients are living longer with advanced kidney cancer, focusing on the safety and effectiveness of new treatments has become even more important. The findings for the combination of CABOMETYX and OPDIVO in the CheckMate -9ER trial make the FDA approval of this combination a notable development for the patient community.”

Filing for Approval in Europe

Exelixis partner, Ipsen Pharma – which has exclusive rights to commercialize and develop CABOMETYX outside of the U.S. and Japan, and Bristol-Myers Squibb Company (BMY) each submitted type II variation applications for CABOMETYX in combination with OPDIVO to the European Medicines Agency (EMA).

On September 12, 2020 the EMA validated the type II variations, confirming the submissions are complete, to begin the EMA’s centralized review process.

On October 27, 2020 Takeda Pharmaceutical and Ono Pharmaceuticals Co., Ltd. submitted a supplemental application to the Japanese Ministry of Health, Labor and Welfare for manufacturing and marketing approval of CABOMETYX in combination with OPDIVO for the treatment of patients with unresectable, advanced, or metastatic RCC. 

About RCC

The American Cancer Society’s 2021 statistics consider kidney cancer as among the top ten most commonly diagnosed forms of cancer among both men and women in the U.S. Clear cell RCC is the most common type of kidney cancer in adults. If detected in its early stages a 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 13%. Approximately 32,000 patients in the U.S. and 71,000 worldwide will require systemic treatment for advanced kidney cancer in 2021. 

About 70% of RCC cases are known as “clear cell” carcinomas, based on histology. 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. These proteins promote tumor angiogenesis (blood vessel growth), growth, invasiveness and metastasis. MET and AXL may provide escape pathways that drive resistance to VEGF receptor inhibitors. 

About CABOMETYX® (cabozantinib)

In the U.S. CABOMETYX tablets are approved for patients with advanced RCC, for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib and for patients with advanced RCC as a first-line treatment in combination with OPDIVO (nivolumab).

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 Limited for the commercialization and clinical development of cabozantinib for all future indications in Japan.

Exelixis holds the exclusive rights to develop and commercialize cabozantinib in the United States. 

To read the important safety information in addition to the warnings and precautions please visit the Exelixis website at: www.exelixis.com/

Prohost Observations

This good news is an important addition to Exelixis’ other good news that has enriched the cancer clinic and its shareholders. We expect EXEL to rebound, which is why we keep it in the Prohost Portfolio. 

To read more about Exelixis please click here.