On March 10, 2020, the FDA accelerated the approval of the immunotherapy combination of nivolumab (Opdivo; Bristol-Myers Squibb) plus ipilimumab (Yervoy; Bristol-Myers Squibb) for patients with hepatocellular carcinoma (HCC) who have previously received sorafenib. Nivolumab and ipilimumab have been previously approved by the FDA for several indications. This new indication was previously granted a breakthrough therapy designation.
The efficacy of the combination was investigated in cohort 4 of the Check- Mate-040 study, a multicenter, multi-cohort, open-label clinical trial conducted in patients with HCC whose disease progressed while receiving or who were intolerant of sorafenib. A total of 49 patients received nivolumab 1 mg/kg in combination with ipilimumab 3 mg/kg every 3 weeks for 4 doses, followed by monotherapy with nivolumab 240 mg every 2 weeks, until disease progression or unacceptable toxicity.
The main efficacy outcome measures were overall response rate (ORR) and duration of response. The ORR was 33% (95% confidence interval, 20-48), with 4 complete responses and 12 partial responses. The duration of response ranged from 4.6 months to >30.5 months, with 31% of responses lasting ≥24 months.
The most common (≥20%) adverse reactions with the drug combination were fatigue, diarrhea, rash, pruritus, nausea, musculoskeletal pain, pyrexia, cough, decreased appetite, vomiting, abdominal pain, dyspnea, upper respiratory tract infection, arthralgia, headache, hypothyroidism, decreased weight, and dizziness.
For patients with HCC, the recommended doses are nivolumab 1 mg/kg, followed by ipilimumab 3 mg/kg on the same day, every 3 weeks for 4 doses, then nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks.
