Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma.
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal, Humanized
/ adverse effects
Antigens, CD
/ metabolism
Antineoplastic Combined Chemotherapy Protocols
/ adverse effects
B7-H1 Antigen
/ antagonists & inhibitors
Double-Blind Method
Female
Humans
Immune Checkpoint Inhibitors
/ adverse effects
Male
Melanoma
/ drug therapy
Middle Aged
Nivolumab
/ adverse effects
Progression-Free Survival
Lymphocyte Activation Gene 3 Protein
Journal
The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562
Informations de publication
Date de publication:
06 01 2022
06 01 2022
Historique:
entrez:
5
1
2022
pubmed:
6
1
2022
medline:
20
1
2022
Statut:
ppublish
Résumé
Lymphocyte-activation gene 3 (LAG-3) and programmed death 1 (PD-1) are distinct inhibitory immune checkpoints that contribute to T-cell exhaustion. The combination of relatlimab, a LAG-3-blocking antibody, and nivolumab, a PD-1-blocking antibody, has been shown to be safe and to have antitumor activity in patients with previously treated melanoma, but the safety and activity in patients with previously untreated melanoma need investigation. In this phase 2-3, global, double-blind, randomized trial, we evaluated relatlimab and nivolumab as a fixed-dose combination as compared with nivolumab alone when administered intravenously every 4 weeks to patients with previously untreated metastatic or unresectable melanoma. The primary end point was progression-free survival as assessed by blinded independent central review. The median progression-free survival was 10.1 months (95% confidence interval [CI], 6.4 to 15.7) with relatlimab-nivolumab as compared with 4.6 months (95% CI, 3.4 to 5.6) with nivolumab (hazard ratio for progression or death, 0.75 [95% CI, 0.62 to 0.92]; P = 0.006 by the log-rank test). Progression-free survival at 12 months was 47.7% (95% CI, 41.8 to 53.2) with relatlimab-nivolumab as compared with 36.0% (95% CI, 30.5 to 41.6) with nivolumab. Progression-free survival across key subgroups favored relatlimab-nivolumab over nivolumab. Grade 3 or 4 treatment-related adverse events occurred in 18.9% of patients in the relatlimab-nivolumab group and in 9.7% of patients in the nivolumab group. The inhibition of two immune checkpoints, LAG-3 and PD-1, provided a greater benefit with regard to progression-free survival than inhibition of PD-1 alone in patients with previously untreated metastatic or unresectable melanoma. Relatlimab and nivolumab in combination showed no new safety signals. (Funded by Bristol Myers Squibb; RELATIVITY-047 ClinicalTrials.gov number, NCT03470922.).
Sections du résumé
BACKGROUND
Lymphocyte-activation gene 3 (LAG-3) and programmed death 1 (PD-1) are distinct inhibitory immune checkpoints that contribute to T-cell exhaustion. The combination of relatlimab, a LAG-3-blocking antibody, and nivolumab, a PD-1-blocking antibody, has been shown to be safe and to have antitumor activity in patients with previously treated melanoma, but the safety and activity in patients with previously untreated melanoma need investigation.
METHODS
In this phase 2-3, global, double-blind, randomized trial, we evaluated relatlimab and nivolumab as a fixed-dose combination as compared with nivolumab alone when administered intravenously every 4 weeks to patients with previously untreated metastatic or unresectable melanoma. The primary end point was progression-free survival as assessed by blinded independent central review.
RESULTS
The median progression-free survival was 10.1 months (95% confidence interval [CI], 6.4 to 15.7) with relatlimab-nivolumab as compared with 4.6 months (95% CI, 3.4 to 5.6) with nivolumab (hazard ratio for progression or death, 0.75 [95% CI, 0.62 to 0.92]; P = 0.006 by the log-rank test). Progression-free survival at 12 months was 47.7% (95% CI, 41.8 to 53.2) with relatlimab-nivolumab as compared with 36.0% (95% CI, 30.5 to 41.6) with nivolumab. Progression-free survival across key subgroups favored relatlimab-nivolumab over nivolumab. Grade 3 or 4 treatment-related adverse events occurred in 18.9% of patients in the relatlimab-nivolumab group and in 9.7% of patients in the nivolumab group.
CONCLUSIONS
The inhibition of two immune checkpoints, LAG-3 and PD-1, provided a greater benefit with regard to progression-free survival than inhibition of PD-1 alone in patients with previously untreated metastatic or unresectable melanoma. Relatlimab and nivolumab in combination showed no new safety signals. (Funded by Bristol Myers Squibb; RELATIVITY-047 ClinicalTrials.gov number, NCT03470922.).
Identifiants
pubmed: 34986285
doi: 10.1056/NEJMoa2109970
pmc: PMC9844513
mid: NIHMS1860413
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Antigens, CD
0
B7-H1 Antigen
0
CD274 protein, human
0
Immune Checkpoint Inhibitors
0
relatlimab
0
Nivolumab
31YO63LBSN
Lymphocyte Activation Gene 3 Protein
0
Lag3 protein, human
0
Banques de données
ClinicalTrials.gov
['NCT03470922']
Types de publication
Clinical Trial, Phase II
Clinical Trial, Phase III
Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
24-34Subventions
Organisme : NCI NIH HHS
ID : P30 CA006973
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Investigateurs
Luciana Bellaquero
(L)
Monica Casalnuovo
(M)
Gabriela Cinat
(G)
Martin Greco
(M)
Nicolas Minatta
(N)
Andrew Hill
(A)
Muhammad Khattak
(M)
Georgina Long
(G)
Amitesh Roy
(A)
Shahneen Sandhu
(S)
Andre Van Der Westhuizen
(A)
Victoria Atkinson
(V)
Christoph Hoeller
(C)
Peter Koelblinger
(P)
Erika Richtig
(E)
Jean-Francois Baurain
(JF)
Vibeke Kruse
(V)
Bart Neyns
(B)
Sergio de Azevedo
(S)
Miilton de Barros E Silva
(M)
Andreia Cristina de Melo
(AC)
Juliana de Menezes
(J)
Veridiana Pires de Camargo
(V)
Gustavo Schvartsman
(G)
Alberto Wainstein
(A)
Bianca Weiss
(B)
Catalin Mihalcioiu
(C)
Wilson Miller
(W)
Xinni Song
(X)
Anna Spreafico
(A)
Robyn Macfarlane
(R)
Pamela Salman
(P)
Luis Matamala
(L)
Fernando Contreras Mejia
(F)
Javier Cuello
(J)
Lars Bastholt
(L)
Henrik Schmidt
(H)
Inge Marie Svane
(IM)
Micaela Hernberg
(M)
Sanna Iivanainen
(S)
Tanja Skytta
(T)
Pia Vihinen
(P)
Jean-Philippe Arnault
(JP)
Stephane Dalle
(S)
Caroline Dutriaux
(C)
Jean-Jacques Grob
(JJ)
Ewa Hainaut-Wierzbicka
(E)
Celeste Lebbe
(C)
Thierry Lesimple
(T)
Laurent Mortier
(L)
Thomas Eigentler
(T)
Anja Gesierich
(A)
Ralf Gutzmer
(R)
Jessica Hassel
(J)
Rudolf Herbst
(R)
Angela Krackhardt
(A)
Cornelia Mauch
(C)
Peter Mohr
(P)
Claudia Pfoehler
(C)
Dirk Schadendorf
(D)
Patrick Terheyden
(P)
Jens Ulrich
(J)
Jochen Utikal
(J)
Ioannis Boukovinas
(I)
Helen Gogas
(H)
Karen Drumea
(K)
Michal Lotem
(M)
Jacob Schachter
(J)
Paolo Ascierto
(P)
Michele Del Vecchio
(M)
Maria Teresa Fierro
(MT)
Michele Maio
(M)
Jacopo Pigozzo
(J)
Carlo Tondini
(C)
Erika Castillo Gutierrez
(E)
Emilio Murillo
(E)
Francisco Medina Soto
(F)
Alejandro Molina Alavez
(A)
Marineé Torres
(M)
Christopher Jackson
(C)
Richard North
(R)
Archana Srivastava
(A)
Kari Jacobsen
(K)
Jacek Mackiewicz
(J)
Piotr Rutkowski
(P)
Tudor Ciuleanu
(T)
Dana Clement
(D)
Michael Schenker
(M)
Daniela Zob
(D)
Lev Demidov
(L)
Yulia Makarova
(Y)
Natalia Musaeva
(N)
Ana Arance Fernandez
(A)
Luis De La Cruz
(L)
Karmele Mujika Eizmendi
(K)
Eva Munoz
(E)
Maria Quindos
(M)
Ainara Soria
(A)
Ana Carneiro
(A)
Hanna Eriksson
(H)
Lars Ny
(L)
Gustav Ullenhag
(G)
Guy Faust
(G)
Christopher Herbert
(C)
Walter Mmeka
(W)
Paul Nathan
(P)
Sophie Papa
(S)
Miranda Payne
(M)
Elizabeth Plummer
(E)
John Wagstaff
(J)
Ashita Waterston
(A)
Thomas Amatruda
(T)
Asim Amin
(A)
Sunil Babu
(S)
Sunandana Chandra
(S)
Charles Cowey
(C)
Brian Dicarlo
(B)
Roxana Dronca
(R)
Zeynep Eroglu
(Z)
Geoffrey Gibney
(G)
John Glaspy
(J)
Mukul Gupta
(M)
Stephen F Hodi
(SF)
Pallavi Kumar
(P)
Christopher Lao
(C)
Evan Lipson
(E)
Svetomir Markovic
(S)
Suresh Nair
(S)
Anna Pavlick
(A)
Montaser Shaheen
(M)
Ronald Steis
(R)
Hussein Tawbi
(H)
Sajeve Thomas
(S)
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Type : CommentIn
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2022 Massachusetts Medical Society.
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