A phase 1/2 trial of an immune-modulatory vaccine against IDO/PD-L1 in combination with nivolumab in metastatic melanoma.
Journal
Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
received:
19
02
2021
accepted:
20
09
2021
pubmed:
11
12
2021
medline:
22
2
2022
entrez:
10
12
2021
Statut:
ppublish
Résumé
Anti-programmed death (PD)-1 (aPD1) therapy is an effective treatment for metastatic melanoma (MM); however, over 50% of patients progress due to resistance. We tested a first-in-class immune-modulatory vaccine (IO102/IO103) against indoleamine 2,3-dioxygenase (IDO) and PD ligand 1 (PD-L1), targeting immunosuppressive cells and tumor cells expressing IDO and/or PD-L1 (IDO/PD-L1), combined with nivolumab. Thirty aPD1 therapy-naive patients with MM were treated in a phase 1/2 study ( https://clinicaltrials.gov/ , NCT03047928). The primary endpoint was feasibility and safety; the systemic toxicity profile was comparable to that of nivolumab monotherapy. Secondary endpoints were efficacy and immunogenicity; an objective response rate (ORR) of 80% (confidence interval (CI), 62.7-90.5%) was reached, with 43% (CI, 27.4-60.8%) complete responses. After a median follow-up of 22.9 months, the median progression-free survival (PFS) was 26 months (CI, 15.4-69 months). Median overall survival (OS) was not reached. Vaccine-specific responses assessed in vitro were detected in the blood of >93% of patients during vaccination. Vaccine-reactive T cells comprised CD4
Identifiants
pubmed: 34887574
doi: 10.1038/s41591-021-01544-x
pii: 10.1038/s41591-021-01544-x
pmc: PMC8904254
doi:
Substances chimiques
Adjuvants, Immunologic
0
B7-H1 Antigen
0
CD274 protein, human
0
Cancer Vaccines
0
Immune Checkpoint Inhibitors
0
Indoleamine-Pyrrole 2,3,-Dioxygenase
0
Nivolumab
31YO63LBSN
Banques de données
ClinicalTrials.gov
['NCT03047928']
Types de publication
Clinical Trial, Phase I
Clinical Trial, Phase II
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2212-2223Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.
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