LBA3 Patritumab deruxtecan (HER3-DXd) in early-stage HR+/HER2- breast cancer: Final results of the SOLTI TOT-HER3 window of opportunity trial

SOLTI TOT-HER3 study (NCT04610528) previously reported the biologic and clinical activity of HER3-DXd, a HER3 directed antibody drug conjugate, across first 30 patients (Prat A, SABCS 2021). Here, we present efficacy safety results all in initial cohort. This window opportunity, multicenter, pre-operative trial enrolled with untreated HR+/HER2- operable (≥1 cm) breast cancer (BC). Patients were categorized based on pre-treatment (pre-) ERBB3 mRNA levels received single dose HER3-DXd (6.4 mg/kg). Primary objective was to evaluate CelTIL score (Nuciforo P, Ann Oncol 2018) variation between pre- post-treatment (C1D21) samples. Clinical, proteomic genomic variables associated changes. Adverse events (AEs) graded according CTCAE v5.0. Overall, 78 77 evaluable for primary endpoint. Baseline characteristics were: mean age 53 years; median tumor size 21 mm; cN0 71%; Ki67 27%. Based pre-ERBB3, tumors classified as high (n=21), medium low (n=21) ultralow (n=14). All PAM50 subtypes identified: Luminal (Lum) A 52%, LumB 41%, HER2-Enriched 3% Basal-like 4%. The overall response rate 45%. increased significantly at C1D21 (mean diff.+6.8, p<0.001). increase observed among responders (p<0.001) but not stable disease (p=0.135). Non-Lum Risk Of Recurrence response. Pre-ERBB3 change or Paired decreased (p<0.001), while did (p=0.13). At C1D21, immune genes induced proliferation suppressed (False Discovery Rate=5%). 74 (95%) any grade AEs. Most common 3-4 AEs neutropenia (n=6), ALT (n=2) diarrhea (n=1). In early BC, led clinically meaningful response, infiltration suppression varied baseline mRNA. profile consistent that reported.