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 email@example.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.