A Phase I Trial Of Talimogene Laherparepvec In Combination With Neoadjuvant Chemotherapy For The Treatment Of Nonmetastatic Triple-Negative Breast Cancer

Purpose: Talimogene laherparepvec (TVEC) is an oncolytic herpes simplex 1 virus approved for treatment of melanoma. We hypothesized intratumoral TVEC may enhance response to neoadjuvant chemotherapy (NAC). This article reports the results of a trial combining NAC with TVEC for triple-negative breast cancer (TNBC).Patients and Methods: Patients with stage II-III TNBC enrolled in a 3+3 phase I trial (NCT02779855) of two TVEC dose levels [DL; DL 1= 10(6) plaque-forming units (PFU) x 5 doses; DL 2 = 10(6) PFUs first dose, then 10(8) PFUs x 4 doses] on weeks 1, 4, 6, 8, and 10 plus weekly paclitaxel (80 mg/m(2)) for 12 weeks, followed by doxorubicin/cyclophosphamide (60/600 mg/m(2)) every 2 weeks for 8 weeks. Postoperative response assessment using residual cancer burden (RCB) was performed. Primary endpoints were safety and MTD. Secondary endpoints were RCBO rate and immune correlates. Dose-limiting toxicity (DLT) rule was grade 3-5 adverse events due to TVEC during first 5 weeks.Results: Nine patients [DL 1 (n = 3); DL 2 (n = 6)] were enrolled. Six had stage II disease, and 3 had stage III (6 clinically N+). No DLTs occurred, and MTD was DL 2. Most common toxicities with TVEC were fever (n = 8), chills (n = 3), hematomas (n = 3), and injection site pain (n = 3). Thromboembolic events (n = 2) and bradycardia (n = 1) occurred during or after NAC. Five patients (55%) achieved RCB0, 2 had RCB1 (22%), and 2 had RCB2 (22%).Conclusions: The addition of TVEC to NAC was feasible at the approved dose, with manageable toxicity. The complete response rate was 55%.