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
Background CAPRA (NCT02565992) evaluated Coxsackievirus A21 (V937) + pembrolizumab for metastatic/unresectable stage IIIB–IV melanoma. 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...
Gespeichert in:
Veröffentlicht in: | Cancer Immunology, Immunotherapy Immunotherapy, 2023-06, Vol.72 (6), p.1405-1415 |
---|---|
Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | Background
CAPRA (NCT02565992) evaluated Coxsackievirus A21 (V937) + pembrolizumab for metastatic/unresectable stage IIIB–IV melanoma.
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
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
+
infiltrates. Surprisingly, the baseline cell density of CD3
+
CD8
−
T cells in the tumor microenvironment was significantly lower in responders compared with nonresponders (
P
= 0.0179).
Conclusions
These findings suggest responses to this combination may be seen even in patients without a typical “immune-active” microenvironment.
Trial registration number
NCT02565992. |
---|---|
ISSN: | 0340-7004 1432-0851 |
DOI: | 10.1007/s00262-022-03314-1 |