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.
Cancer immunology, immunotherapy : CII
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.
Keywords: Clinical trial; Melanoma; Oncolytic virus; Pembrolizumab; V937.
Silk, Ann W; O'Day, Steven; Kaufman, Howard L; Bryan, Jennifer; Norrell, Jacqueline T; Imbergamo, Casey; Portal, Daniella; Zambrano-Acosta, Edwin; Palmeri, Marisa; Fein, Seymour; Wu, Cai; Guerreiro, Leslie; Medina, Daniel; Bommareddy, Praveen K; Zloza, Andrew; Fox, Bernard A; Ballesteros-Merino, Carmen; Ren, Yixin; Shafren, Darren; Grose, Mark; Vieth, Joshua A; and Mehnert, Janice M, "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). Articles, Abstracts, and Reports. 6804.