Talimogene laherparepvec and atezolizumab in HER2-negative breast cancer following neoadjuvant chemotherapy: a window-of-opportunity phase II trial (SOLTI-1503 PROMETEO).

This single-arm, phase II, preoperative window-of-opportunity trial (ClinicalTrials.gov Identifier: NCT03802604) investigated the efficacy and safety of talimogene laherparepvec (T-VEC), an oncolytic virus, with atezolizumab, an anti-PD-L1 antibody, in patients with breast cancer and radiologically and pathologically confirmed residual disease prior to surgery. Eligible patients had triple-negative breast cancer (TNBC) or hormone receptor-positive (HR+)/HER2-negative disease with a high proliferation index (Ki67 ≥ 20%) prior to neoadjuvant chemotherapy. Treatment consisted of one intratumoral injection of T-VEC (10 plaque-forming units [PFU]/mL), followed by four biweekly T-VEC doses (10 PFU/mL) plus atezolizumab (840 mg, intravenously). Among the 28 patients enrolled, 20 patients (71.4%) had HR+/HER2-negative and 8 patients (28.6%) had TNBC. At surgery, 7 patients (26.9%) achieved Residual Cancer Burden (RCB)-0/I (primary endpoint), 12 (46.2%) RCB-II and 7 (26.9%) RCB-III. Safety profile was favorable, with mostly low-grade adverse events and no serious events (secondary endpoint). Therapy induced immune modulation, including increased tumor-infiltrating lymphocytes, elevated PD-L1 expression, and enhanced immune-related gene signatures (exploratory endpoints). The trial met its pre-specified efficacy and safety endpoints. These findings support the feasibility of T-VEC plus atezolizumab as a  preoperative immunotherapy approach for managing HER2-negative residual disease post-neoadjuvant chemotherapy and warrant further exploration in larger trials.