A phase 1b single-arm trial of intratumoral oncolytic virus V937 in combination with pembrolizumab in patients with advanced melanoma: results from the CAPRA study.
Clinical trial
Melanoma
Oncolytic virus
Pembrolizumab
V937
Journal
Cancer immunology, immunotherapy : CII
ISSN: 1432-0851
Titre abrégé: Cancer Immunol Immunother
Pays: Germany
ID NLM: 8605732
Informations de publication
Date de publication:
Jun 2023
Jun 2023
Historique:
received:
21
06
2022
accepted:
15
10
2022
medline:
22
5
2023
pubmed:
30
11
2022
entrez:
29
11
2022
Statut:
ppublish
Résumé
CAPRA (NCT02565992) evaluated Coxsackievirus A21 (V937) + pembrolizumab for metastatic/unresectable stage IIIB-IV melanoma. Patients received intratumoral V937 on days 1, 3, 5, and 8 (then every 3 weeks [Q3W]) and intravenous pembrolizumab 2 mg/kg Q3W from day 8. Primary endpoint was safety. Median time from first dose to data cutoff was 32.0 months. No dose-limiting toxicities occurred; 14% (5/36) of patients experienced grade 3‒5 treatment-related adverse events. Objective response rate was 47% (complete response, 22%). Among 17 responders, 14 (82%) had responses ≥ 6 months. Among 8 patients previously treated with immunotherapy, 3 responded (1 complete, 2 partial). Responses were associated with increased serum CXCL10 and CCL22, suggesting viral replication contributes to antitumor immunity. For responders versus nonresponders, there was no difference in baseline tumor PD-L1 expression, ICAM1 expression, or CD3 These findings suggest responses to this combination may be seen even in patients without a typical "immune-active" microenvironment. NCT02565992.
Sections du résumé
BACKGROUND
BACKGROUND
CAPRA (NCT02565992) evaluated Coxsackievirus A21 (V937) + pembrolizumab for metastatic/unresectable stage IIIB-IV melanoma.
METHODS
METHODS
Patients received intratumoral V937 on days 1, 3, 5, and 8 (then every 3 weeks [Q3W]) and intravenous pembrolizumab 2 mg/kg Q3W from day 8. Primary endpoint was safety.
RESULTS
RESULTS
Median time from first dose to data cutoff was 32.0 months. No dose-limiting toxicities occurred; 14% (5/36) of patients experienced grade 3‒5 treatment-related adverse events. Objective response rate was 47% (complete response, 22%). Among 17 responders, 14 (82%) had responses ≥ 6 months. Among 8 patients previously treated with immunotherapy, 3 responded (1 complete, 2 partial). Responses were associated with increased serum CXCL10 and CCL22, suggesting viral replication contributes to antitumor immunity. For responders versus nonresponders, there was no difference in baseline tumor PD-L1 expression, ICAM1 expression, or CD3
CONCLUSIONS
CONCLUSIONS
These findings suggest responses to this combination may be seen even in patients without a typical "immune-active" microenvironment.
TRIAL REGISTRATION NUMBER
BACKGROUND
NCT02565992.
Identifiants
pubmed: 36445410
doi: 10.1007/s00262-022-03314-1
pii: 10.1007/s00262-022-03314-1
pmc: PMC10198910
doi:
Substances chimiques
pembrolizumab
DPT0O3T46P
Antibodies, Monoclonal, Humanized
0
Types de publication
Clinical Trial, Phase I
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1405-1415Informations de copyright
© 2022. The Author(s).
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