Abstract CT022: Intratumoral plasmid IL-12 and electroporation in pre-treated inoperable locally advanced or recurrent triple-negative breast cancer (TNBC)
Authors: Telli Melinda L. , Zablotsky Kaitlin , Gargosky Sharron E. , Twitty Christopher G. , Wapnir Irene L. 
Published: August 2018

Abstract
Introduction: TNBC accounts for ~15% of breast cancer and is associated with an increased risk of relapse. Emerging data suggest that some TNBC patients benefit from therapies targeting PD-1/PD-L1, but success is limited when patients are heavily pre-treated and lack immunogenic tumors. We designed a protocol to determine whether intratumoral plasmid IL-12 (tavokinogene telseplasmid; tavo) with electroporation (IT-tavo-EP) of inoperable locally advanced or recurrent TNBC would elicit a pro-inflammatory molecular and histological signature in treated as well untreated sites. This gene therapy forces intratumoral expression of the proinflammatory cytokine IL-12 enabling conversion of poorly-immunogenic/low T cell infiltrating tumors into highly inflamed immunologically active lesions.
Methods: Eligible patients had pre-treated TNBC and at least 2 anatomically distinct cutaneous or subcutaneous lesions accessible for injection and electroporation, with or without other regional or distant metastases. 10 patients were planned for enrollment. IT-tavo-EP was administered on Days 1, 5 and 8 of a single 28-day cycle. Tavo was injected intratumorally (based on tumor volume) at a concentration of 0.5 mg/mL and immediately followed by co-localized electroporation (6 pulses at 1500 V/cm with 1-second intervals). Tumor biopsies were obtained at baseline and post-treatment on day 28 of both treated and untreated lesions. TILs, IL-12 expression, and markers of immunologic phenotype by multiparametric IHC and gene expression were assessed. Lesions were measured with calipers pre- and post-treatment. Adverse events and procedure-related pain were recorded.
Results: At the time of abstract submission, 5 patients have completed all study-related procedures and have complete correlative data available. Tavo dose delivered per patient per day ranged from 1.36 to 20 mL. Reported treatment-related adverse events included transient pain associated with electroporation (grade 1) and fatigue (grade 1). Max pain scores (range 0-10) were recorded as an average of 1, with a single patient reporting a 5 at 5 min post-treatment. Treatment-related increase in CD8+ TIL density was observed by intratumoral chromogenic staining (3% at baseline, 11% on day 28 in treated tumors and 5% on day 28 in untreated tumors). Two patients with treatment refractory TNBC received nivolumab as their immediate next therapy and experienced clinically meaningful objective responses. Updated data will be presented.
Conclusions: The present study suggests IT-tavo-EP is a safe and tolerable TIL stimulating therapy of skin and subcutaneous triple-negative tumors. Further study of this therapy in combination with anti-PD-1/PD-L1 antibody therapy is warranted.
Citation Format: Melinda L. Telli, Kaitlin Zablotsky, Sharron E. Gargosky, Christopher G. Twitty, Irene L. Wapnir. Intratumoral plasmid IL-12 and electroporation in pre-treated inoperable locally advanced or recurrent triple-negative breast cancer (TNBC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT022.