Abstract P3-09-04: Phase 2, open-label study of intratumoral tavokinogene telseplasmid (tavo) plus electroporation in combination with intravenous pembrolizumab therapy in patients with inoperable locally advanced or metastatic triple-negative breast cancer (mTNBC) (KEYNOTE- 890/OMS-I141)
Authors: Telli Melinda L. , Wapnir Irene , Devitt Bianca , Cuff Katharine , Soliman Hatem , Vinayak Shaveta , Canton David A. , Twitty Christopher , Foerter Kellie Malloy , Joshi Rohit 
Published: March 2020

Abstract
BACKGROUND: Anti-PD-1 checkpoint inhibitor (CPI) monotherapy has demonstrated modest activity in pre-treated mTNBC, with single digit objective response rates (ORR) observed. Our prior data suggests that local electroporation after intratumoral administration of tavokinogene telseplasmid (IT-tavo-EP), a plasmid encoding the proinflammatory cytokine IL-12, can render CPI non-responsive pre-treated mTNBC sensitive to CPI therapy. The phase II KEYNOTE-890/OMS-I141 study was therefore designed to evaluate IT-tavo-EP and IV pembrolizumab in patients with mTNBC previously treated with chemotherapy +/- CPI therapy.
METHODS: Patients with histologically confirmed inoperable locally advanced or metastatic TNBC with at least 1 line of prior systemic therapy for advanced disease, including prior CPI therapy, were eligible. Patients were required to have RECIST v1.1 measurable disease with at least 1 anatomically distinct cutaneous or subcutaneous lesion accessible for intratumoral injection and electroporation. Scans were obtained every 12 weeks. Patients received pembrolizumab 200 mg IV on day 1 of each 3-week cycle and IT-tavo-EP at a concentration of 0.5 mg/mL and dose volume of ~1/4 of the calculated lesion volume to the accessible lesion(s) on days 1, 5, and 8 every 6 weeks. The primary endpoint of this open-label, non-randomized phase II trial is ORR by investigator review. Secondary endpoints include safety and tolerability of the combined therapy, duration of response, progression-free survival (PFS), immune PFS and overall survival. The correlation between changes in the immune cell subsets and response to treatment was also evaluated.
RESULTS: At the time of abstract submission, 16 of the planned 25 patients have been enrolled and 11 patients completed a post-treatment RECIST v1.1 assessment at the initial 12-week evaluation or discontinued prior to assessment. Patients had a median of 3 prior lines of therapy for advanced disease. Partial responses have been observed in 3 patients (ORR 27.3%), including a deep confirmed response in a patient with multiple liver, bone, skin and nodal metastases and a short disease-free interval following neoadjuvant chemotherapy. Regression of IT-tavo-EP untreated lesions have been observed. Treatment was well tolerated and any grade treatment emergent adverse events (AEs) regardless of attribution were observed in 11 of 16 (68.8%) [grade ≥3 in 6 of 16 (37.5%)]. Only one grade ≥3 AE was attributed to pembrolizumab and none were attributed to IT-tavo or EP. Patients demonstrated immunological responses in blood consistent with an IL-12-associated mechanism of action, including on-treatment reduction of peripheral gMDSC suppressors. Additional biomarker analysis of patient tumor and blood samples are ongoing.
CONCLUSIONS: When compared to the results of KEYNOTE-086, which demonstrated a 5.3% ORR in pretreated mTNBC patients with pembrolizumab monotherapy, our preliminary data from patients who have reached an assessment time-point suggests that IT-tavo-EP may enhance sensitivity to pembrolizumab in this patient population. Updated data will be presented.
Citation Format: Melinda L. Telli, Irene Wapnir, Bianca Devitt, Katharine Cuff, Hatem Soliman, Shaveta Vinayak, David A. Canton, Christopher Twitty, Kellie Malloy Foerter, Rohit Joshi. Phase 2, open-label study of intratumoral tavokinogene telseplasmid (tavo) plus electroporation in combination with intravenous pembrolizumab therapy in patients with inoperable locally advanced or metastatic triple-negative breast cancer (mTNBC) (KEYNOTE- 890/OMS-I141) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-09-04.