Nivolumab is a fully human monoclonal antibody that belongs to an emerging class of cancer immunotherapies termed checkpoint inhibitors. It is given by intravenous infusion over 60 minutes every 2 weeks.
Checkpoint inhibitors are so-called because they act at key checkpoints on the immune system which tumour cells exploit to evade detection and elimination. Unlike chemotherapy and targeted anticancer agents, checkpoint inhibitors act indirectly by allowing the patient's immune system to attack the tumour.
Nivolumab is the first checkpoint inhibitor to target the programmed death-1 (PD-1) receptor. The antibody binds to PD-1 on T cells and blocks the receptor's interaction with PD-L1 and PD-L2, overriding the checkpoint to allow T-cell proliferation and cytokine secretion.
Approval of nivolumab was based on data from two phase III studies.
enrolled patients who had progressed after treatment with the CTLA-4 checkpoint inhibitor ipilimumab (Yervoy), or ipilimumab and a BRAF inhibitor. Participants received open-label treatment with nivolumab or the investigator’s choice of chemotherapy (dacarbazine, or paclitaxel plus carboplatin) until disease progression or unacceptable toxicity.
Confirmed objective responses occurred in 38 (31.7%, 95% CI 23.5–40.8) of the first 120 patients treated with nivolumab, compared with 5 (10.6%, 95% CI 3.5–23.1) of the 47 patients who received chemotherapy.
compared nivolumab with dacarbazine in previously untreated patients without BRAF mutations (n=418). Analysis showed a significantly greater one-year survival rate of 72.9% in the nivolumab group compared with 42.1% in the dacarbazine group (hazard ratio for death 0.42, 99.79% CI 0.25–0.73, p<0.001), with a median progression-free survival of 5.1 months and 2.2 months, respectively.
Serious drug-related adverse events were less common with nivolumab than chemotherapy in both studies: 5% versus 9% in CheckMate 037 and 11.7% versus 17.6% in CheckMate 066.
The most common adverse effects of nivolumab were fatigue, rash, pruritus, diarrhoea and nausea, most of which were mild to moderate.