Assessment of immune and clinical efficacy after intralesional PV-10 in injected and uninjected metastatic melanoma lesions.

Melanoma/Skin Cancers
Session Type and Session Title: 
Poster Highlights Session, Melanoma/Skin Cancers
Abstract Number: 
J Clin Oncol 32:5s, 2014 (suppl; abstr 9028)
Amod Sarnaik, Georgina Crago, Hao Liu, Krithika Nandakumar Kodumudi, Amy Weber, Timothy McCardle, Jeffrey S. Weber, Shari Pilon-Thomas; H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL; Moffitt Cancer Center, Comprehensive Melanoma Research Center, Tampa, FL

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Abstract Disclosures


Background: Intralesional (IL) therapy is under investigation to treat dermal and subcutaneous metastatic cancer. In our murine model, IL injection of PV-10 (10% Rose Bengal) induced regression of injected and uninjected “bystander” melanomas. We observed a consistent increase in anti-tumor T cell responses following IL PV-10 in the mouse model, supporting an immune-based mechanism by which PV-10 mediates regression of uninjected “bystander” tumors. Methods: We translated these findings into a pilot clinical trial that enrolled 8 patients with dermal and/or subcutaneous metastatic melanoma. Two study lesions in each patient were sampled by biopsy pre-treatment; one of the two lesions was injected with IL PV-10, then both residual sites were completely excised. We compared tumors before and after treatment with H&E staining to determine pathologic complete response (pCR), and we confirmed results with MelanA immunohistochemistry. Peripheral blood mononuclear cells (PBMC) before and after IL PV-10 were phenotyped for activation markers by flow cytometry. Results: Treatment with IL PV-10 led to pCR in the post-treatment biopsies of both PV10-injected and uninjected study lesions in 4 of the 8 patients, and all 8 exhibited at least partial regression of the injected lesion. IL PV-10 was associated with an increase in circulating cytotoxic CD3+/CD8+ T cells (paired t test, p=0.008). Pre and post PV-10 treated PBMC from one patient were re-stimulated with autologous tumor in vitro. Compared to pre-treatment, PV-10 treatment produced an increase in tumor-specific interferon-gamma release by ELISA. Six of 8 patients had metastatic disease refractory to previous ipilimumab, anti-PD-1 and/or vemurafenib therapy. Four of these 6 patients exhibited pCR to PV10 in both the injected and uninjected lesions. Conclusions: IL PV-10 treatment can lead to systemic anti-melanoma immunity and pCR in injected and uninjected lesions including treatment-refractory tumors. Further studies are ongoing to determine the mechanism by which PV-10 increases tumor-specific T cell responses as well as to establish the interaction of intralesional PV-10 with combination checkpoint protein inhibition. Clinical trial information: NCT01760499.