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Oncolytic T-VEC virotherapy plus neoadjuvant chemotherapy in nonmetastatic triple-negative breast cancer: a phase 2 trial

Nature Medicine volume 29, pages 450–457 (2023)Cite this article

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An Author Correction to this article was published on 17 March 2023

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Abstract

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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Fig. 1: DFS curve for the study population.
Fig. 2: Time point biomarker analyses.
Fig. 3: Predictive biomarkers for response.
Fig. 4: Flow cytometry analysis of circulating lymphocytes.

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Data availability

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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Acknowledgements

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.

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Authors and Affiliations

  1. Department of Breast Oncology, Moffitt Cancer Center, Tampa, FL, USA

    Hatem Soliman, Hyo Han, Ricardo Costa, Marie C. Lee, Aixa Soyano, Avan Armaghani, Nazanin Khakpour, Susan Hoover, John Kiluk, Christine Laronga, Hung Khong & Brian Czerniecki

  2. Clinical Trials Office, Moffitt Cancer Center, Tampa, FL, USA

    Deanna Hogue

  3. Department of Radiology, Moffitt Cancer Center, Tampa, FL, USA

    Blaise Mooney, Bethany Niell, Angela Williams, Alec Chau, Shannon Falcon & Robert J. Weinfurtner

  4. Department of Pathology, Moffitt Cancer Center, Tampa, FL, USA

    Marilin Rosa

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Contributions

H.S. was responsible for study design and oversight, protocol and manuscript authorship, data acquisition, data interpretation and manuscript approval. H.K., M.C.L., H.H., M.R., A.W., D.H., S.F., A.S., N.K., J.K., C.L., A.A., R.C., R.J.W., B.M., A.C., B.N., S.H. and B.C. were responsible for study design, data acquisition and data interpretation, and manuscript critical review, editing and approval.

Corresponding author

Correspondence to Hatem Soliman.

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Competing interests

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.

Peer review

Peer review information

Nature Medicine thanks S.-H. Jung, H. Kaufman, M. Kok and A. van Akkooi for their contribution to the peer review of this work. Primary Handling Editor: Ulrike Harjes, in collaboration with the Nature Medicine team.

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Extended data

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.

Extended Data Table 1 Patient-level clinico-pathological data table
Full size table

Supplementary information

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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

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