As reported in the Journal of Clinical Oncology by Thomas Yau, MD, and colleagues, findings in a cohort of the phase I/II CheckMate 040 trial indicated the activity of nivolumab/cabozantinib with or without ipilimumab in patients with advanced hepatocellular carcinoma.
Thomas Yau, MD
Study Details
In the international open-label trial, 71 patients who were treatment-naive, sorafenib-intolerant, or whose disease had progressed on sorafenib were randomly assigned between July 2017 and January 2018 to receive nivolumab plus cabozantinib with (n = 35) or without (n = 36) ipilimumab. The doublet group received nivolumab at 240 mg once every 2 weeks plus cabozantinib at 40 mg once daily; the triplet group received nivolumab at 3 mg/kg every 2 weeks, cabozantinib at 40 mg once daily, and ipilimumab at 1 mg/kg once every 6 weeks. Treatment continued until disease progression or unacceptable toxicity.
Responses
At database lock (end of September 2020), median follow-up was 32.0 months (range = 28.5–36.2 months). Investigator-assessed objective response was observed in 6 patients (17%, 95% confidence interval [CI] = 6%–33%) in the doublet group and in 10 (29%, 95% CI = 15%–46%) in the triplet group, with complete response seen in 1 patient in each group. Stable disease was observed in an additional 23 patients (64%) and 19 patients (54%); disease control rates were 81% and 83%. Median durations of response were 8.3 months (95% CI = 6.9 months to not estimable) and not reached (95% CI = 0.0 months to not estimable).
In the doublet and triplet groups, median progression-free survival on blinded independent central review was 5.1 months (95% CI = 2.8–10.9 months) and 4.3 months (95% CI = 3.6–11.9 months); rates at 12 and 24 months were 29% and 32% and 11% and 29%, respectively. Median overall survival was 20.2 months (95% CI = 13.1–32.2 months) and 22.1 months (95% CI = 15.2 months to not estimable); rates at 12 and 24 months were 70% and 70% and 39% and 45%, respectively.
KEY POINTS
- Objective response rates were 17% with doublet therapy and 29% with triplet therapy, with median response durations of 8.3 months and not reached.
- Median overall survival was 20.2 and 22.1 months.
Adverse Events
Grade 3 or 4 treatment-related adverse events occurred in 50% of patients in the doublet group and 74% of the triplet group. The most common were diarrhea (11%), hypertension (11%), and increased alanine aminotransferase (AST; 8%) in the doublet group, and increased AST (23%), hypertension (17%), and increased lipase (17%) in the triplet group. Treatment-related serious adverse events occurred in 11% and 34% of patients. Treatment-related adverse events led to discontinuation of treatment in 11% and 23% of patients. No treatment-related deaths were reported.
The investigators concluded, “Nivolumab plus cabozantinib with or without ipilimumab showed encouraging preliminary antitumor activity and had consistent safety profiles with those established for the individual drugs in patients with advanced hepatocellular carcinoma.”
Dr. Yau, of the University of Hong Kong, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Bristol Myers Squibb, Ono Pharmaceutical Company, Ltd, and Exelixis, Inc. For full disclosures of the study authors, visit ascopubs.org.
