T-VEC Oncolytic Virus Shows Promise in Breast Cancer and Nonmelanoma Skin Cancer Trials

A single-arm, phase II preoperative window-of-opportunity trial 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. The trial met its pre-specified efficacy and safety endpoints.

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. Among the 28 patients enrolled, 20 patients (71.4%) had HR+/HER2-negative and 8 patients (28.6%) had TNBC. Treatment consisted of one intratumoral injection of T-VEC (106 plaque-forming units [PFU]/mL), followed by four biweekly T-VEC doses (108 PFU/mL) plus atezolizumab (840 mg, intravenously).

At surgery, 7 patients (26.9%) achieved Residual Cancer Burden (RCB)-0/I, the primary endpoint. Additionally, 12 patients (46.2%) achieved RCB-II and 7 patients (26.9%) achieved RCB-III. The safety profile was favorable, with mostly low-grade adverse events and no serious events. Therapy induced immune modulation, including increased tumor-infiltrating lymphocytes, elevated PD-L1 expression, and enhanced immune-related gene signatures.

In a separate retrospective study at a single institution, patients with Merkel cell carcinoma (MCC) or squamous cell carcinoma (SCC) were treated with T-VEC between May 2016 and May 2023. Ten MCC and three SCC patients were eligible. Four MCC patients and all three SCC patients received concurrent pembrolizumab.

Overall, six patients achieved complete response (CR), one had partial response (PR), and six had progressive disease (PD). Of the six patients who achieved CR, two recurred at 8 and 56 months. Those without recurrence had a durable response at a median follow-up of 25 months. Nearly 50% of participants had a complete response, and two-thirds of responders remained relapse-free at the time of follow-up.

T-VEC is a modified version of the JS17 strain of HSV-1 in which neurovirulence genes have been replaced by the human granulocyte-macrophage colony-stimulating factor (hGM-CSF) gene, which can instigate an antitumor T-cell response. Additional modifications facilitate antigen-presentation and prolonged host response. These modifications help initiate and maintain an immune response that is more robust and specific to tumor cells, while minimizing adverse effects in nontumor tissues. T-VEC received FDA approval for treatment of Stage III and IV melanoma in 2015.

The findings from the breast cancer trial 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. The retrospective study investigators noted that some observed responses in NMSC are not attributable to T-VEC alone due to high usage rates of immune therapy, and future work should expand to larger cohorts and focus on its use with and without immune therapy.