332TiP SOLTI-1907 ATREZZO: Targeting hormonal receptor negative (HR-) or PAM50 non-luminal disease with atezolizumab in combination with trastuzumab and vinorelbine in HER2+ metastatic breast cancer (MBC)

Multiple options remain available after progression on Trastuzumab (T), pertuzumab (P) or T-DM1 in HER2+ MBC. The use of immune checkpoint inhibitors to enhance antitumor immunity in HER2+ BC has become an attractive strategy. Preclinical evidence suggests that immune-mediated resistance to T can be overcome by combination with immune checkpoint inhibitors. Besides, previous studies of gene expression have shown that Basal-like and HER2-enriched are associated with higher expression of immune-related genes or higher TILS, compared to luminal subtypes. Additionally, immune infiltration in HER2+ BC is associated with chemo/antiHER2 responsiveness and potential benefit from anti-PD-1/PD-L1 inhibitors. We hypothesize that combining anti-PD-L1 therapy with T and vinorelbine might improve outcomes in non-luminal disease within HER2+ advanced BC. ATREZZO is a Simon 2-stage, single arm phase II trial, with two independent cohorts (PD-L1+ and PD-L1-). The trial will include pre- or post-menopausal female or male patients with locally advanced, or metastatic HER2+ BC that are HR- or PAM50 non-luminal and that have progressed to T, P or T-DM1 either in metastatic and/or early setting. Treatment consists in Atezolizumab IV 1200 mg every 3 weeks combined with T and Vinorelbine on standard doses. Tumor assessments will be performed every 9 weeks. Primary objective is to evaluate the Overall Response Rate according to RECIST v 1.1. Secondary endpoints include clinical benefit rate, overall survival, progression free survival, duration of response, time to response and incidence, duration and severity of adverse events, and further correlative molecular analyses. Interim and final analysis will be performed independently in each cohort. Sixteen Spanish sites will participate, recruitment started in April 2021. Trial identification: NCT04759248. SOLTI innovative cancer research. Funding and Atezolizumab was granted by Roche.