Abstract OT2-06-03: A phase 2 study of intratumoral tavokinogene telseplasmid (tavo) plus electroporation with pembrolizumab in patients with inoperable locally advanced or metastatic triple negative breast cancer

Abstract

Abstract Triple negative breast cancer (TNBC) accounts for 10-20% of breast cancer diagnoses and is associated with a high risk of recurrence and a more aggressive course in the metastatic setting. Emerging data suggest that some patients with TNBC could benefit from the addition of immune-based therapy due to the important role of tumor infiltrating lymphocytes (TILs) on outcome. Reports show that early-stage TNBC patients with at least 50% TILs demonstrate longer disease-free survival. Additionally, immune-modulating therapies, like the anti-PD-1/PD-L1 monoclonal antibodies, have demonstrated modest activity in the pre-treated metastatic TNBC population with objective response rates (ORR) <10%, but appear to require an immunogenic tumor, characterized by CD8+ TILs, in order to be effective. Plasmid IL-12 (tavo) with electroporation (tavo- EP) is a gene therapy approach yielding sustained intratumoral expression of the proinflammatory cytokine IL-12. Combining tavo-EP with an anti-PD-1 therapy, such as pembrolizumab, may improve responses for TNBC subjects by potentially converting poorly-immunogenic/low TIL tumors into high TIL/immune-responsive tumors while providing a favorable side-effect profile. OMS-I141 is a phase 2, non-randomized, study of intratumoral tavo-EP with pembrolizumab in patients with locally-advanced, inoperable, metastatic and/or treatment-refractory TNBC. Key inclusion criteria include documented inoperable locally advanced or metastatic TNBC, at least 1 prior line of approved systemic chemotherapy or immunotherapy and an accessible lesion for intratumoral injection and electroporation. Eligible subjects will receive intratumoral tavo-EP to the accessible lesions on Days 1, 5 and 8 every 6 weeks and intravenous (IV) pembrolizumab (200 mg) on Day 1 of each 3-week cycle. The primary objective of the study is to assess the ORR by blinded independent central review based on RECIST v 1.1. Secondary objectives include assessment of safety and tolerability of the combined treatment, duration of response (DOR), ORR (investigator-assessed), immune ORR (iORR), progression-free survival (PFS), immune PFS (iPFS) and overall survival (OS). A Simon 2-Stage design will be employed and a total of 25 patients will be accrued. In Stage 1 up to 15 subjects will be enrolled. If the number of responders meet the pre-specified number (N ≥ 1/15), then the enrollment for Stage 2 will include an additional 10 subjects (for a total of ≥ 6 responders out of 25 subjects). For more information regarding the study, contact OncoSec at info@oncosec.com. Citation Format: Telli ML, Wapnir I, Vinayak S, Chang J, Alemany C, Twitty C, Gargosky S. A phase 2 study of intratumoral tavokinogene telseplasmid (tavo) plus electroporation with pembrolizumab in patients with inoperable locally advanced or metastatic triple negative breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT2-06-03.