The results indicate that combining an oncolytic virus (T-VEC) with immunotherapy (atezolizumab) achieved complete responses in patients who typically do not respond to available treatments. Although these findings are not sufficient to change clinical practice for this indication, the study provides solid proof of concept, demonstrating that it is possible to activate the immune system in resistant tumours and advance new immunotherapy strategies.
The study, published in Nature Communications, was coordinated by Aleix Prat, 4CB director and head of the IDIBAPS Translational Genomics and Targeted Therapies in Solid Tumours Group; and Tomás Pascual, medical oncologist in the 4CB Breast Cancer Unit, researcher in the same IDIBAPS group, and SOLTI Board member.
Impact of residual disease on prognosis
HR+/HER2-negative breast cancer is the most common subtype and often requires neoadjuvant chemotherapy to shrink the tumour and improve post-surgical prognosis.
However, when residual disease persists after this treatment, relapse risk increases significantly, with no specific options to intensify therapy.
The PROMETEO (SOLTI-1503) study addresses this precise clinical scenario. For the first time, it evaluates an oncolytic virus (T-VEC) combined with immunotherapy (atezolizumab) in the "window of opportunity" – the brief period between neoadjuvant treatment and surgery. This approach enabled detailed study of tumour biology through multiple samples obtained during the process.
Complete responses in treatment-resistant patients
The trial included 28 patients with HER2-negative breast cancer and residual disease post-chemotherapy. T-VEC plus atezolizumab proved safe and well tolerated. Notably, 7 of 28 patients (25%) achieved pathological complete response (pCR) – no tumour cells in the surgical specimen – a highly significant outcome in a population where such responses are rare.
Subtype analysis showed a 30.0% pCR rate in HR+/HER2– tumours versus 12.5% in triple-negative disease – particularly relevant since all patients had prior chemotherapy without complete response. Achieving new pCRs in this context is extraordinary. Robust immune activation was also observed, with increased tumour-infiltrating lymphocytes (TILs), higher PD-L1 expression, and immune signalling activation, confirming the strategy's ability to remodel the tumour microenvironment.
With ~4-year median follow-up, no relapses occurred among pCR patients, confirming complete response's prognostic value in this population.
Aleix Prat, PROMETEO principal investigator and Clínic Cancer and Blood Disorders Institute (ICAMS) director, highlights: "PROMETEO was the first trial exploring intratumoural immunotherapy plus PD-L1 blockade in residual breast cancer pre-surgery. These studies are particularly challenging, but success shows academic research can open new treatment paths and generate high-value biological/clinical knowledge."
Tomás Pascual, PROMETEO co-principal investigator, adds: "PROMETEO shows even typically poorly immunogenic tumours like hormone-positive ones can respond to local immunotherapy strategies." This research, also part of his University of Barcelona doctoral thesis supervised by Dr. Prat, opens new exploration avenues: "This finding launches a highly promising research line for most breast cancer patients with few options beyond endocrine therapy. Window-of-opportunity trials by academic groups generate valuable evidence and train next-generation clinical researchers."
Proof of concept opening new research lines
The study's translational research – analysing all samples and tumour biological characterisation – was conducted in Dr. Prat's IDIBAPS Translational Genomics and Targeted Therapies in Solid Tumours Group laboratory.
PROMETEO experience will model new immunotherapy combinations and intratumoural strategies for breast cancer and other solid tumours.
Sponsored by SOLTI, the study included 28 patients with Amgen and Roche support.
Study reference:
Pascual T, Vidal M, Cejalvo JM, Vega E, Sanfeliu E, Villacampa G, Ganau S, Parreño AMJ, Zamora E, Miranda I, Delgado A, Bermejo B, Seguí E, Brasó-Maristanty F, de la Cruz-Merino L, Juan M, Galván P, Gonzàlez-Farré X, Chillara S, Villagrasa P, Pfefferle AD, O'Connell CE, Ferrero-Cafiero JM, Oliveira M, Perou CM, Prat A. Talimogene laherparepvec and atezolizumab in HER2-negative breast cancer following neoadjuvant chemotherapy: a window-of-opportunity phase II trial (SOLTI-1503 PROMETEO). Nat Commun. 2026 Feb 16. doi: 10.1038/s41467-026-69222-5.
