FDA Announces Nivolumab Dose Change for RCC, NSCLC, Metastatic Melanoma

September 28, 2016

The FDA announced a modification to the recommended dosage regimen for nivolumab (Opdivo) for renal cell carcinoma (RCC), metastatic melanoma, and non–small-cell lung cancer (NSCLC).

The US Food and Drug Administration (FDA) announced a modification to the recommended dosage regimen for nivolumab (Opdivo) for renal cell carcinoma (RCC), metastatic melanoma, and non–small-cell lung cancer (NSCLC). Nivolumab was originally approved at a single dose of 3 mg/kg intravenously (IV) every 2 weeks. For all three diseases, the new dosage is 240 mg IV every 2 weeks until disease progression or intolerable toxicity.

According to the FDA announcement, the approval of the dosage modification was based on population pharmacokinetics analyses and dose/exposure-response analyses that demonstrated the comparability of the pharmacokinetics exposure, safety, and efficacy of the proposed new dosing regimen with the 3 mg/kg every 2 weeks regimen.

Using simulations in the population pharmacokinetics model, the FDA determined that exposure to nivolumab at a dose of 240 mg every 2 weeks was similar to the 3 mg/kg every 2 weeks dose-less than a 6% difference in exposure. The differences in exposure are not likely to have a clinically meaningful effect on safety and efficacy, since dose/exposure response relationships appear to be relatively flat in these three indications.

The FDA announcement noted that the dose of nivolumab used in combination with ipilimumab for melanoma will not be changing. That dose will remain at 1 mg/kg IV followed by ipilimumab on the same day every 3 weeks for four doses. However, once the ipilimumab treatment is completed, the recommended nivolumab dose will be the new dosage of 240 mg every 2 weeks until disease progression or intolerable toxicity.

Finally, the recommended dose for classical Hodgkin lymphoma will remain 3 mg/kg IV every 2 weeks until disease progression or intolerable toxicity.