Dataset Information

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.

ABSTRACT:

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.

SUBMITTER: Silk AW

PROVIDER: S-EPMC10198910 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Publications

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.

Silk Ann W AW O'Day Steven J SJ Kaufman Howard L HL Bryan Jennifer J Norrell Jacqueline T JT Imbergamo Casey C Portal Daniella D Zambrano-Acosta Edwin E Palmeri Marisa M Fein Seymour S Wu Cai C Guerreiro Leslie L Medina Daniel D Bommareddy Praveen K PK Zloza Andrew A Fox Bernard A BA Ballesteros-Merino Carmen C Ren Yixin Y Shafren Darren D Grose Mark M Vieth Joshua A JA Mehnert Janice M JM

Cancer immunology, immunotherapy : CII 20221129 6

<h4>Background</h4>CAPRA (NCT02565992) evaluated Coxsackievirus A21 (V937) + pembrolizumab for metastatic/unresectable stage IIIB-IV melanoma.<h4>Methods</h4>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.<h4>Results</h4>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-relat ...[more]

PMID: 36445410

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Project description:BackgroundIntratumoral administration of V937, a bioselected, genetically unmodified coxsackievirus A21, has previously demonstrated antitumor activity in patients with advanced melanoma as monotherapy and in combination with the programmed cell death 1 (PD-1) antibody pembrolizumab. We report results from an open-label, single-arm, phase 1b study (NCT02307149) evaluating V937 plus the cytotoxic T-lymphocyte antigen 4 inhibitor ipilimumab in patients with advanced melanoma.MethodsAdult patients (aged ≥18 years) with histologically confirmed metastatic or unresectable stage IIIB/C or IV melanoma received intratumoral V937 on days 1, 3, 5, 8, and 22 and every 3 weeks (Q3W) thereafter for up to 19 sets of injections plus intravenous ipilimumab 3 mg/kg Q3W administered for four doses starting on day 22. Imaging was performed at screening, on days 43 and 106 and every 6 weeks thereafter; response was assessed by immune-related response criteria per investigator assessment. Primary endpoints were safety in all treated patients and objective response rate (ORR) in all treated patients and in patients with disease that progressed on prior anti-PD-1 therapy.ResultsFifty patients were enrolled and treated. ORR was 30% (95% CI 18% to 45%) among all treated patients, 47% (95% CI 23% to 72%) among patients who had not received prior anti-PD-1 therapy, and 21% (95% CI 9% to 39%) among patients who had experienced disease progression on prior anti-PD-1 therapy. Tumor regression occurred in injected and non-injected lesions. Median immune-related progression-free survival was 6.2 months (95% CI 3.5 to 9.0 months), and median overall survival was 45.1 months (95% CI 28.3 months to not reached). The most common treatment-related adverse events (AEs) were pruritus (n=25, 50%), fatigue (n=22, 44%), and diarrhea (n=16, 32%). There were no V937-related dose-limiting toxicities and no treatment-related grade 5 AEs. Treatment-related grade 3 or 4 AEs, all of which were considered related to ipilimumab, occurred in 14% of patients (most commonly dehydration, diarrhea, and hepatotoxicity in 4% each).ConclusionsResponses associated with intratumoral V937 plus ipilimumab were robust, including in the subgroup of patients who had experienced disease progression on prior anti-PD-1 therapy. Toxicities were manageable and consistent with those of the individual monotherapies.

Dataset Information

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

Methods

Results

Conclusions

Trial registration number

Publications

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.

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