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
© 2022. The Author(s)..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:72 |
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| Enthalten in: |
Cancer immunology, immunotherapy : CII - 72(2023), 6 vom: 17. Juni, Seite 1405-1415 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Silk, Ann W [VerfasserIn] |
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| Links: |
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| Themen: |
Antibodies, Monoclonal, Humanized |
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| Anmerkungen: |
Date Completed 22.05.2023 Date Revised 26.04.2024 published: Print-Electronic ClinicalTrials.gov: NCT02565992 Citation Status MEDLINE |
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| doi: |
10.1007/s00262-022-03314-1 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
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| 245 | 1 | 2 | |a A phase 1b single-arm trial of intratumoral oncolytic virus V937 in combination with pembrolizumab in patients with advanced melanoma |b results from the CAPRA study |
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| 500 | |a ClinicalTrials.gov: NCT02565992 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022. The Author(s). | ||
| 520 | |a BACKGROUND: CAPRA (NCT02565992) evaluated Coxsackievirus A21 (V937) + pembrolizumab for metastatic/unresectable stage IIIB-IV melanoma | ||
| 520 | |a 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 | ||
| 520 | |a 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) | ||
| 520 | |a CONCLUSIONS: These findings suggest responses to this combination may be seen even in patients without a typical "immune-active" microenvironment | ||
| 520 | |a TRIAL REGISTRATION NUMBER: NCT02565992 | ||
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