124O Patritumab deruxtecan (HER3-DXd) in hormonal receptor-positive/HER2-negative (HR+/HER2-) and triple-negative breast cancer (TNBC): Results of part B of SOLTI TOT-HER3 window of opportunity trial
Bibliographic record
Abstract
We previously reported the biologic and clinical activity of HER3-DXd in Part A of SOLTI TOT-HER3 in patients (pts) with HR+/HER2- early breast cancer (BC) after a single dose of 6.4 mg/kg (Prat A. et al, ESMO BREAST 2022). Here, we present the main efficacy and safety results of TOT-HER3 Part B. In Part B of this window of opportunity trial, 2 cohorts of pts with treatment-naïve HER2- primary operable BC, ≥1 cm by US or MRI were recruited. Pts received a single dose of HER3-DXd 5.6 mg/kg. Primary objective was the variation in tumor cellularity and tumor-infiltrating lymphocytes (CelTIL) score between pre- and post-treatment tumors. Associations of baseline clinical and biological features with CelTIL changes and overall response rate (ORR) by US were explored. Thirty-seven pts with HER2- BC were recruited (HR+ n=20; TNBC n=17). Mean age was 53 (30-81); 20 (54%) were pre-menopausal; mean tumor size was 21 mm (range 10-81 mm); and median Ki67 was 30% (12-95%). In response to treatment with HER3-DXd CelTIL score increased and decreased in 21 (57%) and 16 (43%) pts, respectively. Overall, a statistically significant change in CelTIL was observed between paired samples overall (p=0.046) and in TNBC (p=0.016), but not in HR+ (p=0.793). ORR by US in all patients was 32% (35% in TNBC and 30% in HR+). The absolute change in CelTIL was associated with ORR (AUC=0.693; p=0.049). Baseline ERBB3 levels were not associated with CelTIL change or ORR. HER3-DXd induced high expression of immune-related genes (e.g., PD1, CD8 and CD19), and suppressed proliferation-related genes. Thirty-one (84%) patients reported AEs at any grade. Most common AEs were nausea, fatigue, alopecia, diarrhea, constipation and vomiting. Grade 3 treatment-related nausea occurred in 1 patient. No ILD events were reported. A single dose of HER3-DXd was associated with clinical response and significant biological changes in HER2- tumors, irrespective of baseline ERBB3 levels. The safety profile was consistent with that previously reported. Additional correlative analysis will be presented on site.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".