Exelixis, Inc. (NASDAQ:EXEL) today announced phase 1/2 clinical trial results from the combination of cabozantinib (CABOMETYX®) and nivolumab (Opdivo®) with or without ipilimumab (Yervoy®) in advanced hepatocellular carcinoma (HCC). Data from the cabozantinib combination cohort of the CheckMate 040 trial will be 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 is being held in San Francisco, California, January 23-25, 2020. The data will also be included in Poster Session B from 12:00 – 1:30 p.m. PT and 4:30 – 5:30 p.m. PT on January 24.
CheckMate 040 is a phase 1/2 study that includes an exploratory cohort of patients with advanced HCC who were either treatment naïve (41%) or who were intolerant to or had progressed on prior sorafenib therapy (59%). For the 36 patients treated with the combination of cabozantinib and nivolumab (17 treatment naïve [47%] and 19 with prior sorafenib therapy [53%]), 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 [34%] and 23 with prior sorafenib therapy [66%]), 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.
“We are pleased to report clinically meaningful responses from CheckMate 040 cohort 6 in advanced liver cancer patients treated with these cabozantinib combinations,” said Thomas Yau, M.D., Clinical Associate Professor, Department of Medicine, The University of Hong Kong, and a lead investigator of the trial. “Patients with advanced liver cancer need new and effective treatment options. Based on the cohort six findings, cabozantinib in combination with immunotherapy offers a potentially powerful and attractive new treatment approach that warrants further study in advanced liver cancer populations.”
No new safety signals were identified in this combination cohort. Treatment-related grade 3 or 4 adverse events were observed in 47% of the cabozantinib and nivolumab group; events occurring in more than 5% of patients were hypertension (11%), diarrhea (11%), aspartate aminotransferase (AST) increase (8%) and lipase increase (6%). Treatment-related grade 3 or 4 adverse events were observed in 71% of the cabozantinib, nivolumab and ipilimumab group; events occurring in more than 5% of patients were AST increase (23%), lipase increase (17%), ALT increase (17%), hypertension (17%) and palmar-plantar erythrodysaesthesia (9%). Discontinuation rates due to treatment-related adverse events were 11% for the cabozantinib and nivolumab group and 20% for the cabozantinib, nivolumab and ipilimumab group.
“As we just marked one year since CABOMETYX was approved for the treatment of patients with advanced hepatocellular cancer who have previously received sorafenib, it’s exciting to be sharing new data featuring cabozantinib as part of a combination with immunotherapies,” said Gisela Schwab, M.D., President, Product Development and Medical Affairs and Chief Medical Officer, Exelixis. “The promising clinical activity observed for these cohorts in CheckMate 040 suggests combination therapy with cabozantinib and immunotherapy may potentially benefit patients with this aggressive disease.”