155TiP A randomised phase II trial of neoadjuvant multi-agent chemotherapy (CHT) OR patritumab deruxtecan (HER3-DXd; U3-1402) +/- endocrine therapy (ET) for high-risk hormone receptor-positive (HR+/HER2-) early breast cancer (EBC): SOLTI-2103 VALENTINE trial

The decision of neoadjuvant treatment for high-risk HR+/HER2- EBC remains a challenge. Despite the availability both CHT and ET, risk recurrence persists over time, highlighting need additional therapeutic strategies. In TOT-HER3 trial, we have shown that single dose HER3-DXd, first-in-class HER3 directed antibody drug conjugate, is associated with clinical response, increased immune infiltration proliferation suppression, as well consistent manageable safety profile in patients (pts) HR+/HER2-negative early breast cancer (Prat et al. ESMO Breast 2022). These data informed design VALENTINE trial HER3-DXd setting. parallel, exploratory, three-arm, randomised, open-label, exploratory study pts primary operable Ki67 IHC ≥ 20% and/or high genomic (defined by gene signature), aiming to evaluate benefit biological effects (with/without letrozole (LET)) treatment. A total 120 naïve will be randomly assigned 2:2:1 ratio receive (1) (5.6 mg/kg) every 21 days 6 cycles; (2) plus daily LET +/- LHRH analogs (3) standard care consisting 4 cycles EC/AC (epirubicin 90 mg/m2 or doxorubicin 60 cyclophosphamide 600 14/21 days) followed weekly 80mg/m2 paclitaxel during 12 weeks. endpoint rate pathological complete response (ypT0/is ypN0) at surgery. Baseline, on-treatment (C2D1), surgical specimens collected molecular characterization evaluation (ERBB3 expression, IHC; CelTIL change, research-based PAM50 subtypes). Additional samples pharmacokinetic, circulating biomarkers also collected. Secondary endpoints include residual burden, overall rate, invasive disease-free survival 3 5 years safety. An interim final analysis are pre-planned. EudraCT 2022-001181-36. NCT05569811, First Posted: February 18, 2021. SOLTI Cancer Research Group.