title: U.S. FDA Approval Summary: Nivolumab for Treatment of Unresectable or Metastatic Melanoma Following Progression on Ipilimumab.
abstract: On December 22, 2014, the FDA granted accelerated approval to nivolumab (OPDIVO; Bristol-Myers Squibb) for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Approval was based on a clinically meaningful, durable objective response rate (ORR) in a non-comparative analysis of 120 patients who received 3 mg/kg of nivolumab intravenously every 2 weeks with at least 6-month follow-up in an ongoing, randomized, open-label, active-controlled clinical trial. The ORR as assessed by a blinded independent review committee per RECIST v1.1 was 31.7% (95% confidence interval, 23.5-40.8). Ongoing responses were observed in 87% of responding patients, ranging from 2.6+ to 10+ months. In 13 patients, the response duration was 6 months or longer. The risks of nivolumab, including clinically significant immune-mediated adverse reactions (imARs), were assessed in 268 patients who received at least one dose of nivolumab. The FDA review considered whether the ORR and durations of responses were reasonably likely to predict clinical benefit, the adequacy of the safety database, and systematic approaches to the identification, description, and patient management for imARs in product labeling.Clin Cancer Res; 23(14); 3484-8. ©2017 AACR.
authors.affiliation: Office of Hematology and Oncology Products (OHOP), Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland. Maitreyee.hazarika@fda.hhs.gov.
authors.forename: Maitreyee
authors.initials: M
authors.lastname: Hazarika
authors.affiliation: Office of Hematology and Oncology Products (OHOP), Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Meredith K
authors.initials: MK
authors.lastname: Chuk
authors.affiliation: Office of Hematology and Oncology Products (OHOP), Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Marc R
authors.initials: MR
authors.lastname: Theoret
authors.affiliation: Office of Biostatistics, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Sirisha
authors.initials: S
authors.lastname: Mushti
authors.affiliation: Office of Biostatistics, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Kun
authors.initials: K
authors.lastname: He
authors.affiliation: Office of Hematology and Oncology Products (OHOP), Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Shawna L
authors.initials: SL
authors.lastname: Weis
authors.affiliation: Office of Hematology and Oncology Products (OHOP), Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Alexander H
authors.initials: AH
authors.lastname: Putman
authors.affiliation: Office of Hematology and Oncology Products (OHOP), Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Whitney S
authors.initials: WS
authors.lastname: Helms
authors.affiliation: Office of Clinical Pharmacology, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Xianhua
authors.initials: X
authors.lastname: Cao
authors.affiliation: Office of Clinical Pharmacology, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Hongshan
authors.initials: H
authors.lastname: Li
authors.affiliation: Office of Clinical Pharmacology, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Office of Clinical Pharmacology, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Joel
authors.initials: J
authors.lastname: Welch
authors.affiliation: Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Laurie
authors.initials: L
authors.lastname: Graham
authors.affiliation: Office of Hematology and Oncology Products (OHOP), Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Meredith
authors.initials: M
authors.lastname: Libeg
authors.affiliation: Office of Biostatistics, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Rajeshwari
authors.initials: R
authors.lastname: Sridhara
authors.affiliation: Office of Hematology and Oncology Products (OHOP), Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Patricia
authors.initials: P
authors.lastname: Keegan
authors.affiliation: Office of Hematology and Oncology Products (OHOP), Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Richard
authors.initials: R
authors.lastname: Pazdur
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000074324:Ipilimumab / Q000008:administration & dosage; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D000077594:Nivolumab; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000235:genetics*; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000911:Antibodies, Monoclonal; D000074324:Ipilimumab; D047428:Protein Kinase Inhibitors; D000077594:Nivolumab; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf