Exelixis reported results from CheckMate 040, a phase 1/2, open-label trial investigating cabozantinib (Cabometyx) and nivolumab (Opdivo) with or without ipilimumab (Yervoy) in patients with advanced HCC with and without chronic viral hepatitis who are naïve, intolerant to or who have progressed during sorafenib therapy. Data from the cabozantinib combination cohort of the CheckMate 040 trial were presented on Friday, January 24 during Rapid Abstract Session B from 7:00 – 7:45 a.m. PT at the 2020 American Society of Clinical Oncology’s Gastrointestinal Cancers Symposium (ASCO GI), which was held in San Francisco, California, January 23-25, 2020.
Patients in the cabozantinib combination cohort were randomized 1:1 to receive either nivolumab plus cabozantinib or nivolumab plus cabozantinib and ipilimumab. Primary endpoints include ORR (investigator assessed using RECIST v1.1) and safety/tolerability. For the 36 patients treated with the combination of cabozantinib and nivolumab (17 treatment naïve and 19 with prior sorafenib therapy ), the investigator-assessed objective response rate (ORR) was 19%, and disease control rate (DCR) was 75%. Median progression-free survival (PFS) was 5.4 months, and median overall survival was 21.5 months. For the 35 patients treated with the combination of cabozantinib, nivolumab and ipilimumab (12 treatment naïve and 23 with prior sorafenib therapy ), the investigator-assessed ORR was 29%, and DCR was 83%. Median PFS was 6.8 months, and median overall survival had not yet been reached.
Cabometyx tablets are approved in the U.S. 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.
Cabometyx targets three key drivers of RCC and HCC tumorigenesis—MET, AXL, and VEGFR1
In RCC and HCC tumor cells and cells of the tumor microenvironment, MET, AXL, and VEGF are overexpressed. These receptors are involved in normal and pathologic processes such as tumor angiogenesis, invasiveness, metastasis, and immunomodulation of the tumor microenvironment.
Liver cancer is a leading cause of cancer death worldwide, accounting for more than 700,000 deaths and 800,000 new cases each year. In the U.S., the incidence of liver cancer has more than tripled since 1980. HCC is the most common form of liver cancer, making up about three-fourths of the estimated 43,000 new cases in the U.S. in 2020. HCC is the fastest-rising cause of cancer-related death in the U.S. Without treatment, patients with advanced HCC usually survive less than 6 months.