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Record W4397007234 · doi:10.1016/j.esmoop.2024.103146

159TiP TROPION-Breast04: Phase (ph) III study of neoadjuvant (neoadj) datopotamab deruxtecan (Dato-DXd) + durvalumab (D) followed by adjuvant (adj) D vs standard of care (SoC) in treatment-naïve, triple-negative (TN) and HR-low/HER2- breast cancer (BC)

2024· article· en· W4397007234 on OpenAlexaffabout
Sibylle Loibl, S.M. Tolaney, P. Schmid, Barbara Pistilli, Rebecca Dent, Jamil Asselah, Q. Liu, Jane Meisel, Naoki Niikura, Y.H. Park, G. Werutsky, Giampaolo Bianchini, J.C. Andersen, R. Kozarski, N. Rokutanda, Heather L. McArthur

Bibliographic record

VenueESMO Open · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicBreast Cancer Treatment Studies
Canadian institutionsMcGill University Health Centre
Fundersnot available
KeywordsDurvalumabMedicineInternal medicineStandard of careAdjuvantOncologyCancerImmunotherapyNivolumab

Abstract

fetched live from OpenAlex

SoC for patients (pts) with treatment-naïve, Stage II–III TNBC is neoadj pembrolizumab (pembro) + chemotherapy (CT) followed by surgery and adj pembro. However, there remains an unmet need to develop a treatment approach to improve pathological complete response (pCR) rates and long-term survival while reducing traditional CT-associated toxicity. Dato-DXd comprises a humanised, anti-TROP2 IgG1 monoclonal antibody conjugated to a potent topoisomerase I inhibitor via a plasma-stable, tetrapeptide-based, tumour-selective cleavable linker. Dato-DXd + D demonstrated durable responses in unresectable, advanced TNBC in the Ph Ib/II BEGONIA study. The ongoing Ph3 TROPION-Breast03 study is evaluating Dato-DXd ± D vs SoC as adj therapy in pts with Stage I–III TNBC and residual invasive disease at the time of surgery after neoadj treatment. TROPION-Breast04 (NCT06112379) aims to determine if outcomes can be improved with neoadj Dato-DXd + D followed by adj D vs SoC in treatment-naïve pts with early-stage TNBC or HR-low/HER2– BC. TROPION-Breast04 is a Ph3, 2-arm, parallel-group, randomised, open-label, multicentre study. ∼1728 pts (≥18 years) with previously untreated, Stage II–III, unilateral / bilateral, primary invasive TNBC or HR-low (ER and/or PR 1%–<10%; neither HR ≥10%)/HER2– BC and ECOG PS 0–1, will be randomised 1:1 into 1 of 2 arms (Table), stratified by lymph node status, tumour stage, HR status, and region. Primary endpoints: pCR and event-free survival. Secondary endpoints: overall survival, distant disease-free survival, patient-reported outcomes, pharmacokinetics, immunogenicity, safety/tolerability. Enrolment is planned in 26 countries/regions; recruitment is active in Canada, South Korea and Taiwan at the time of abstract submission.Table: 159TiPTROPION-Breast04 treatment armsTherapyNeoadjuvantSurgeryAdjuvantExperimental armDato-DXd[a + durvalumabb:8 cyclesIndicatedDurvalumabb:9 cycles ± olaparibc* chemotherapy†Control armdPembrolizumab + carboplatin + paclitaxel: 4 cycles followed by Pembrolizumab + cyclophosphamide + doxorubicin or epirubicin: 4 cyclesIndicatedDurvalumabb:9 cycles ± olaparibc* chemotherapy†*In combination with durvalumab/pembrolizumab in pts with gBRCA+ tumours and residual disease; not concurrently with chemo.†In combination with durvalumab/pembrolizumab in pts with residual disease. a6 mg/kg IV every 3 weeks (Q3W); b1120 mg IV Q3W; c300 mg orally twice daily for 1 year; dSoC doses. Open table in a new tab *In combination with durvalumab/pembrolizumab in pts with gBRCA+ tumours and residual disease; not concurrently with chemo.†In combination with durvalumab/pembrolizumab in pts with residual disease. a6 mg/kg IV every 3 weeks (Q3W); b1120 mg IV Q3W; c300 mg orally twice daily for 1 year; dSoC doses. NCT06112379. Medical writing support for the development of this abstract, under the direction of the authors, was provided by Werner Gerber of Ashfield MedComms (Fourways, South Africa), an Inizio company. AstraZeneca PLC in collaboration with Daiichi Sankyo. Pharmaceutical, biotech, or other commercial company; AstraZeneca PLC in collaboration with Daiichi Sankyo.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.455
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.010
GPT teacher head0.314
Teacher spread0.304 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designObservational
Domainnot available
GenreEmpirical

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".

Quick stats

Citations1
Published2024
Admission routes2
Has abstractyes

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