Abstract OT1-01-01: SOLTI-1503 PROMETEO: Combination of talimogene laherparepvec (T-VEC) with atezolizumab in patients with residual breast cancer after standard neoadjuvant multi-agent chemotherapy
Authors: Pascual Tomás , Villagrasa Patricia , Vidal María J , Ganau Sergi , Bermejo Begoña , Julve Ana , Zamora Esther , Miranda Ignacio , Vega Estela , Marquez Cristina , Oliveira Mafalda , Cejalvo Juan Miguel , de la Cruz Luis , Juan Manel , Canes Jordi , Gonzalez Xavier , Prat Aleix 
Published: March 2020

Abstract
Background: New strategies as immune blockade inhibitors and oncolytic viruses are opening new possibilities in cancer therapy. Preliminary results in melanoma showed that the combination of Talimogene Laherparevec (T-VEC) with an anti PD-L1 or anti CTLA4 has greater efficacy than either therapy alone, without additional safety concerns beyond those expected for each individual agent. The presence of residual cancer after neoadjuvant chemotherapy (NAC) in early breast cancer (BC) patients is an unmet medical need. We hypothesize that combining T-VEC with Atezolizumab may offer clinical benefit in the preoperative setting for early BC patients with intermediate to high risk of recurrence who present residual disease (RD) after standard NAC.
Methods: PROMETEO is an open-label, multicenter trial of T-VEC in combination with Atezolizumab in patients with residual disease after completing standard NAC. 30 patients with triple negative breast cancer (TNBC) or Luminal B-like/Her2- (ER/PR&gt;10% and Ki-67 ≥30% or ER/PR 1-10% and Ki-67 ≥20%) will be included. RD must be confirmed by core-biopsy and have a diameter ≥ 15mm measured by magnetic resonance imaging. Adequate organ function and ECOG PS 0-1 are required. T-VEC is administered intratumorally in week 1 (106 plaque-forming units/mL [pfu/mL]), then in week 4 and every 2 weeks thereafter (108 pfu/mL) for four injections. Atezolizumab (840 mg) is administered intravenously every 2 weeks for four infusions, beginning in week 4. BC surgery will be carried out 1 to 3 weeks after completion of study treatment. Primary objective is to evaluate the effect of T-VEC + Atezolizumab by comparing the expression of a gene signature tracking activated CD8 T-cells between RD at surgery and RD after NAC. We expect a relative increase of ≥20% in the expression of this CD8 T-cell gene signature in 20% of patients or more, defined as the mean expression of PRF1, CD8A, GZMM, CD8B and FLT3LG, between post and pre-treatment samples. Secondary endpoints include pathologic complete response rate and residual cancer burden, objective response rate, and safety. Two safety data reviews - after 4 and 10 patients complete treatment - are planned. A total of 4 sites in Spain are participating in the trial. To date, 4 patients have been included and it is expected to complete the first safety data review in September 2019. The study recruitment is planned to be completed by October 2020.
Clinical trial identification: NCT03802604
Citation Format: Tomás Pascual, Patricia Villagrasa, María J Vidal, Sergi Ganau, Begoña Bermejo, Ana Julve, Esther Zamora, Ignacio Miranda, Estela Vega, Cristina Marquez, Mafalda Oliveira, Juan Miguel Cejalvo, Luis de la Cruz, Manel Juan, Jordi Canes, Xavier Gonzalez, Aleix Prat. SOLTI-1503 PROMETEO: Combination of talimogene laherparepvec (T-VEC) with atezolizumab in patients with residual breast cancer after standard neoadjuvant multi-agent chemotherapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT1-01-01.