Talimogene laherparepvec (T-VEC) is an oncolytic virus hypothesized to enhance triple-negative breast cancer (TNBC) responses to neoadjuvant chemotherapy (NAC). This article describes the phase 2 trial of T-VEC plus NAC (ClinicalTrials.gov ID: NCT02779855). Patients with stage 2–3 TNBC received five intratumoral T-VEC injections with paclitaxel followed by doxorubicin and cyclophosphamide and surgery to assess residual cancer burden index (RCB). The primary end point was RCB0 rate. Secondary end points were RCB0–1 rate, recurrence rate, toxicity and immune correlates. Thirty-seven patients were evaluated. Common T-VEC toxicities were fevers, chills, headache, fatigue and injection site pain. NAC toxicities were as expected. Four thromboembolic events occurred. The primary end point was met with an estimated RCB0 rate = 45.9% and RCB0–1 descriptive rate = 65%. The 2-year disease-free rate is equal to 89% with no recurrences in RCB0–1 patients. Immune activation during treatment correlated with response. T-VEC plus NAC in TNBC may increase RCB0–1 rates. These results support continued investigation of T-VEC plus NAC for TNBC.
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The RNAseq dataset is available on dbGAP (https://dbgap.ncbi.nlm.nih.gov/) to researchers with an approved dbGAP profile as outlined on the website, using the accession number phs003199.v1.p1. All other datasets generated during and/or analysed during the current study can be requested from the corresponding author. Requests will be responded to within 4 weeks.
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This work was supported by the digital pathology, tissue processing, molecular genomics, bioinformatics/biostatistics and flow cytometry cores at the Moffitt Cancer Center funded by a Moffitt Cancer Center support grant no. P30-CA076292. We thank A. Aldrich for the flow cytometry data acquisition.
Funding for the trial was provided by Amgen. H.S. has received consulting fees from AstraZeneca, Novartis, Seattle Genetics, PUMA, Sanofi and Eisai; licensing fees for intellectual property from Celyad Oncology; and institutional research funding from Amgen. H.K. has sat on the scientific advisory board for Celcuity; holds equities in Agenus, TG Therapeutics, Vexart, Lipocine, Mustang Bio, MEI Pharma and Tiziana Life Sciences; and has received institutional research support from AstraZeneca. M.C.L. has received research funding from Elucent Medical. S.H. has sat on the advisory board of Devicor/Mammotome. H.H. has received fees for advisory and speaker bureau activities from Lilly, Novartis and Immunomedics. B.C. has received advisory fees from Merit Oncology and has intellectual property rights with Immunorestoration. M.R. has received speaker fees from Roche. A.W., D.H., S.F., A.S., N.K., J.K., C.L., A.A., R.C., R.J.W., B.M. and A.C. declare no competing interests.
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Extended Data Fig. 1 OptSNE analysis of baseline circulating lymphocytes.
The image shows the identified lymphocyte clusters of closely related populations along with their dominant cell surface markers. The first panel shows which clusters of cells are from responders (events in red) versus non-responders (events in yellow). Four clusters highlighted in the figure are particularly enriched for events from responders. The first three clusters appear to be natural killer T cell subsets (NKT) and the fourth cluster a B cell predominant one.
Extended Data Fig. 2 Gene expression associated with poor response.
Volcano plot showing statistically significant differentially expressed individual genes represented by red dots.
Extended Data Fig. 3 Gating illustration.
A representative ancestry gating figure for the various populations quantified.
Study protocol document.
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Soliman, H., Hogue, D., Han, H. et al. Oncolytic T-VEC virotherapy plus neoadjuvant chemotherapy in nonmetastatic triple-negative breast cancer: a phase 2 trial. Nat Med 29, 450–457 (2023). https://doi.org/10.1038/s41591-023-02210-0