Results of this trial led to an accelerated FDA approval of Opdivo (nivolumab) and Yervoy (ipilimumab) in March to treat this specific patient population.
Treatment with Opdivo (nivolumab) with Yervoy (ipilimumab) was manageably safe and resulted in a promising response in patients with advanced hepatocellular carcinoma (HCC) previously treated with Nexavar (sorafenib).
“Based on the results of this study, nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every three weeks followed by nivolumab 240 mg every 2 weeks or 480 mg every four weeks received accelerated approval in the United States as a second-line therapy for HCC,” the study authors wrote. “Investigation of this combination is underway as a first-line therapy in patients with HCC.”
The combination of Opdivo and Yervoy were previously proven to be effective in treating other tumor types including non-small cell lung cancer, renal cell carcinoma, microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer and melanoma. The CheckMate 040 trial, with findings published in JAMA Oncology, focused on the safety and efficacy of this treatment in patients with advanced HCC who were either intolerant of or had issues with Nexavar.
This phase 1/2 randomized clinical trial included 148 patients (median age, 60 years; 81% men) from 31 centers in 10 countries or territories in Europe, Asia and North America. Patients were randomly assigned to one of three arms:
Patients in arm A and arm B were then given 240 mg of Opdivo intravenously every two weeks after completion of their assigned regimens. Coprimary end points of this trial included tolerability, safety and objective response rate (ORR). In addition, tumors were assessed every six weeks until 48 weeks by CT or MRI, which was then conducted every 12 weeks until disease progression. Median follow-up was conducted for a median of 30.7 months.
The ORR assessed by investigators was 32% in arm A, 27% in arm B and 29% in arm C. Although the median duration of response was not achieved in arm A, it was achieved in arm B (15.2 months) and arm C (21.7 months).
Adverse events related to the assigned treatment occurred in 94% of patients in arm A, 71% of those in arm B and 79% of patients in arm C. One treatment-related death occurred in arm A as a result of grade 5 pneumonitis, or lung tissue inflammation.
“To our knowledge, this is the first report of nivolumab-ipilimumab combination therapy in the treatment of advanced HCC,” the study authors wrote. “Nivolumab plus ipilimumab provided a robust clinical benefit in patients treated with sorafenib.”
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