On September 13, 2016, the U.S. Food and Drug Administration modified the dosage regimen for nivolumab (Opdivo, Bristol-Myers Squibb Co.) for the currently approved indications for renal cell carcinoma, metastatic melanoma, and non-small cell lung cancer. The currently approved recommended dosage regimens were modified to 240 mg intravenously (IV) every two weeks.
The approval modifies the Dosage and Administration section of the labeling by replacing the single dose regimen of nivolumab (3 mg/kg intravenously every two weeks) with the new recommended regimen of 240 mg IV every two weeks until disease progression or intolerable toxicity for renal cell carcinoma, metastatic melanoma, and non-small cell lung cancer.
In addition, the nivolumab dosing regimen in combination with ipilimumab for melanoma will remain the same (nivolumab 1 mg/kg IV, followed by ipilimumab on the same day, every 3 weeks for 4 doses). However, after completion of ipilimumab, the recommended nivolumab dose will be 240 mg every two weeks until disease progression or intolerable toxicity. The recommended dose for classical Hodgkin lymphoma remains 3 mg/kg IV, every 2 weeks until disease progression or intolerable toxicity.
The approval was based on population pharmacokinetics analyses and dose/exposure-response analyses demonstrating the comparability of the pharmacokinetics exposure, safety, and efficacy of the proposed new dosing regimen with the previously approved regimen.
Based on simulations by the population pharmacokinetics model, FDA determined that the overall exposure at 240 mg every two weeks flat dose is similar (less than 6% difference) to 3 mg/kg every two weeks. These 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.
Full prescribing information is available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/125554s017s018lbl.pdf
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