Background: 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 manuscript reports the results of a trial combining NAC with TVEC for triple-negative breast cancer (TNBC). Methods: Stage II-III TNBC patients enrolled in a 3+3 phase 1 trial (NCT02779855) of 2 TVEC dose levels (DL) (DL 1 = 10⁶ plaque-forming units (PFUs) × 5 doses; DL 2 = 10⁶ PFUs first dose, then 10⁸ PFUs × 4 doses) on weeks 1,4,6,8, 10 plus weekly paclitaxel (80 mg/m²) for 12 weeks, followed by doxorubicin/cyclophosphamide (60/600 mg/m²) every 2 weeks for 8 weeks. Postoperative response assessment using residual cancer burden (RCB) was performed. Primary endpoints were safety and maximum tolerated dose (MTD). Secondary endpoints were RCB0 rate and immune correlates. Dose limiting toxicity (DLT) rule was grade 3-5 adverse events due to TVEC during first 5 weeks. Findings: 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 dose 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%). Interpretation: The addition of TVEC to NAC was feasible at the approved dose, with manageable toxicity. The complete response rate was 55%.