Abstract PO1-20-13: TROPION-Breast04: A phase 3 study of neoadjuvant datopotamab deruxtecan (Dato-DXd) + durvalumab followed by adjuvant durvalumab vs the standard of care in treatment-naive early-stage triple negative or HR-low/HER2– breast cancer
Bibliographic record
Abstract
Abstract Background: The current standard of care for patients (pts) with treatment-naive Stage II–III triple-negative breast cancer (TNBC) is neoadjuvant pembrolizumab + anthracycline/taxane/platinum-based chemotherapy followed by surgery and adjuvant pembrolizumab monotherapy. However, among pts who received the combination of pembrolizumab and chemotherapy in the KEYNOTE-522 trial (NCT03036488), 28% ultimately discontinued therapy due to treatment-related adverse events, and 37% had residual disease at the time of surgery, which was associated with poor outcomes. Consequently, there remains an unmet need to develop a treatment approach that improves pathologic complete response (pCR) rates and long-term survival while reducing chemotherapy-associated toxicity in pts with early-stage TNBC. Dato-DXd is a TROP2-directed antibody-drug conjugate that consists of a humanized anti-TROP2 IgG1 monoclonal antibody conjugated to a potent topoisomerase I (Topo-I) inhibitor via a plasma stable tetrapeptide-based tumor-selective cleavable linker. Dato-DXd monotherapy has demonstrated a manageable safety profile and encouraging preliminary efficacy in pts with metastatic TNBC in the Phase 1 TROPION-PanTumor01 study (NCT03401385), with a confirmed objective response rate (ORR) of 32% in all pts and 44% in Topo-I inhibitor-naive pts with measurable disease at baseline. The combination of Dato-DXd with durvalumab has demonstrated durable responses in unresectable locally advanced or metastatic TNBC in the Phase 1b/2 BEGONIA study (NCT03742102), with an ORR of 79%, median duration of response of 15.5 months and median progression-free survival of 13.8 months. The ongoing Phase 3 TROPION-Breast03 trial (NCT05629585) is evaluating Dato-DXd ± durvalumab versus standard-of-care therapy as adjuvant treatment in pts with Stage I–III TNBC with residual invasive disease at the time of surgery after neoadjuvant treatment. The TROPION-Breast04 trial aims to determine if improved efficacy and safety can be achieved with neoadjuvant Dato-DXd + durvalumab followed by adjuvant durvalumab, compared with the pembrolizumab-based standard of care regimen in pts with previously untreated TNBC or hormone receptor-low (estrogen and/or progesterone receptor 1% to <10%; neither hormone receptor may be ≥10%)/HER2-negative (HR-low/HER2–) breast cancer. Trial design: TROPION-Breast04 (NCT06112379) is an ongoing Phase 3, 2-arm, parallel-group, randomized, open-label, multicenter, global trial. Approximately 1728 adults (aged ≥18 years) with previously untreated histologically confirmed Stage II–III unilateral or bilateral primary invasive TNBC or HR-low/HER2– breast cancer per AJCC edition 8 as assessed by the investigator, and an ECOG PS of 0 or 1, will be randomized 1:1 into one of two arms: neoadjuvant Dato-DXd + durvalumab followed by adjuvant durvalumab-based therapy, or neoadjuvant pembrolizumab + chemotherapy followed by adjuvant pembrolizumab-based therapy (full treatment details are provided in the Table). Randomization will be stratified by lymph node status, tumor stage, HR status, and geographic region. Pts with distant disease and any prior surgery, radiotherapy, or systemic anticancer therapy will be excluded from the study. The primary endpoints are pCR and event-free survival. The key secondary endpoint is overall survival; others are distant disease-free survival, patient reported outcomes, pharmacokinetics, immunogenicity, and safety/tolerability. TROPION-Breast04 opened for enrolment in November 2023. Citation Format: Heather McArthur, Sara Tolaney, Sibylle Loibl, Rebecca Dent, Peter Schmid, Jamil Asselah, Erwei Song, Naoki Niikura. TROPION-Breast04: A phase 3 study of neoadjuvant datopotamab deruxtecan (Dato-DXd) + durvalumab followed by adjuvant durvalumab vs the standard of care in treatment-naive early-stage triple negative or HR-low/HER2– breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-20-13.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.004 |
| Insufficient payload (model declined to judge) | 0.007 | 0.002 |
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 source (direct Gemma or distilled Codex), 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".