Περίληψη:
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.
Συγγραφείς:
Tawbi, Hussein A.
Schadendorf, Dirk
Lipson, Evan J. and
Ascierto, Paolo A.
Matamala, Luis
Gutierrez, Erika Castillo and
Rutkowski, Piotr
Gogas, Helen J.
Lao, Christopher D.
De
Menezes, Juliana Janoski
Dalle, Stephane
Arance, Ana
Grob,
Jean-Jacques
Srivastava, Shivani
Abaskharoun, Mena
Hamilton,
Melissa
Keidel, Sarah
Simonsen, Katy L.
Sobiesk, Anne Marie
and Li, Bin
Hodi, F. Stephen
Long, V, Georgina and
RELATIVITY-047 Investigators
