Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma.

The New England journal of medicine (2015-06-02)
James Larkin, Vanna Chiarion-Sileni, Rene Gonzalez, Jean Jacques Grob, C Lance Cowey, Christopher D Lao, Dirk Schadendorf, Reinhard Dummer, Michael Smylie, Piotr Rutkowski, Pier F Ferrucci, Andrew Hill, John Wagstaff, Matteo S Carlino, John B Haanen, Michele Maio, Ivan Marquez-Rodas, Grant A McArthur, Paolo A Ascierto, Georgina V Long, Margaret K Callahan, Michael A Postow, Kenneth Grossmann, Mario Sznol, Brigitte Dreno, Lars Bastholt, Arvin Yang, Linda M Rollin, Christine Horak, F Stephen Hodi, Jedd D Wolchok

Nivolumab (a programmed death 1 [PD-1] checkpoint inhibitor) and ipilimumab (a cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4] checkpoint inhibitor) have been shown to have complementary activity in metastatic melanoma. In this randomized, double-blind, phase 3 study, nivolumab alone or nivolumab plus ipilimumab was compared with ipilimumab alone in patients with metastatic melanoma. We assigned, in a 1:1:1 ratio, 945 previously untreated patients with unresectable stage III or IV melanoma to nivolumab alone, nivolumab plus ipilimumab, or ipilimumab alone. Progression-free survival and overall survival were coprimary end points. Results regarding progression-free survival are presented here. The median progression-free survival was 11.5 months (95% confidence interval [CI], 8.9 to 16.7) with nivolumab plus ipilimumab, as compared with 2.9 months (95% CI, 2.8 to 3.4) with ipilimumab (hazard ratio for death or disease progression, 0.42; 99.5% CI, 0.31 to 0.57; P<0.001), and 6.9 months (95% CI, 4.3 to 9.5) with nivolumab (hazard ratio for the comparison with ipilimumab, 0.57; 99.5% CI, 0.43 to 0.76; P<0.001). In patients with tumors positive for the PD-1 ligand (PD-L1), the median progression-free survival was 14.0 months in the nivolumab-plus-ipilimumab group and in the nivolumab group, but in patients with PD-L1-negative tumors, progression-free survival was longer with the combination therapy than with nivolumab alone (11.2 months [95% CI, 8.0 to not reached] vs. 5.3 months [95% CI, 2.8 to 7.1]). Treatment-related adverse events of grade 3 or 4 occurred in 16.3% of the patients in the nivolumab group, 55.0% of those in the nivolumab-plus-ipilimumab group, and 27.3% of those in the ipilimumab group. Among previously untreated patients with metastatic melanoma, nivolumab alone or combined with ipilimumab resulted in significantly longer progression-free survival than ipilimumab alone. In patients with PD-L1-negative tumors, the combination of PD-1 and CTLA-4 blockade was more effective than either agent alone. (Funded by Bristol-Myers Squibb; CheckMate 067 number, NCT01844505.).

Product Number
Product Description

Formaldehyde-12C solution, 20% in H2O, 99.9 atom % 12C
Formaldehyde solution, ACS reagent, 37 wt. % in H2O, contains 10-15% Methanol as stabilizer (to prevent polymerization)
Formaldehyde solution, meets analytical specification of USP, ≥34.5 wt. %
Formaldehyde solution, for molecular biology, BioReagent, ≥36.0% in H2O (T)
Formaldehyde solution, for molecular biology, 36.5-38% in H2O