FDA Grants Accelerated Approval to Nivolumab and Ipilimumab Combination for Hepatocellular Carcinoma
On March 10, 2020, the U.S. Food and Drug Administration (FDA) granted accelerated approval to the combination of nivolumab and ipilimumab (Opdivo® and Yervoy®) for patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib.
Efficacy of the combination was investigated in cohort 4 of CHECKMATE-040 (NCT01658878), a multicenter, multiple cohort, open-label trial conducted in patients with HCC who progressed on or were intolerant to sorafenib. A total of 49 patients received nivolumab 1 mg/kg in combination with ipilimumab 3 mg/kg every three weeks for four doses, followed by single-agent nivolumab 240 mg every two weeks until disease progression or unacceptable toxicity.
The main efficacy outcome measures were overall response rate and duration of response as determined by blinded independent central review using RECIST v1.1. ORR was 33% (n = 16; 95% CI = 20, 48) with four complete responses and 12 partial responses. Response duration ranged from 4.6–30.5+ months, with 31% of responses lasting at least 24 months.
The most common adverse reactions (³20%) with nivolumab in combination with ipilimumab are 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 HCC, the recommended doses are nivolumab 1 mg/kg followed by ipilimumab 3 mg/kg on the same day every three weeks for four doses, then nivolumab 240 mg every two weeks or 480 mg every four weeks.
View the full prescribing information for nivolumab and ipilimumab.
The indication received accelerated approval based on overall response rate and duration of response. Continued approval may be contingent on verification and description of clinical benefit in confirmatory trials.
The review used Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment.
FDA had previously granted breakthrough therapy designation for this indication, and the application received priority review. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions—Drugs and Biologics.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.
For assistance with single-patient investigational new drugs, healthcare professionals may contact the Oncology Center of Excellence’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.