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Record W4397007022 · doi:10.1016/j.esmoop.2024.103282

261TiP TROPION-Breast05: Phase (Ph) III study of datopotamab deruxtecan (Dato-DXd) ± durvalumab (D) vs chemotherapy (CT) + pembrolizumab (pembro) in patients (pts) with PD-L1+ locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC)

2024· article· en· W4397007022 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueESMO Open · 2024
Typearticle
Languageen
FieldMedicine
TopicCancer Immunotherapy and Biomarkers
Canadian institutionsPrincess Margaret Cancer Centre
Fundersnot available
KeywordsPembrolizumabDurvalumabMedicineChemotherapyMetastatic melanomaDocetaxelInternal medicineOncologyRadiologyImmunotherapyCancer

Abstract

fetched live from OpenAlex

Standard of care for pts with metastatic PD-L1+ (Combined Positive Score [CPS] ≥10) TNBC is pembro + CT, but prognosis remains poor. Dato-DXd comprises a humanised, anti-TROP2 IgG1 mAb conjugated to a potent topoisomerase I (Topo-I) inhibitor via a plasma-stable, tetrapeptide-based, tumour-selective cleavable linker. D is a high-affinity, human IgG1 mAb that blocks interaction of PD-L1 with PD-1 and CD80 by binding to PD-L1. In the Ph1 TROPION-PanTumor01 study, Dato-DXd demonstrated a manageable safety profile and encouraging efficacy in heavily pretreated metastatic TNBC. In the PhIb/2 BEGONIA study, Dato-DXd + D showed durable responses in unresectable advanced TNBC. TROPION-Breast05 (NCT06103864) will evaluate Dato-DXd ± D vs investigator’s choice of CT (ICC) + pembro in PD-L1+ locally recurrent inoperable or metastatic TNBC. The Ph3, randomized, open-label, 3-arm, multicentre TROPION-Breast05 study will randomise ∼625 pts (≥18 years) with histologically/cytologically documented, locally recurrent inoperable or metastatic PD-L1+ (CPS ≥10) TNBC not previously treated with CT or targeted systemic anticancer therapy. Pts with active brain metastases, or prior exposure to Topo-I ADC or TROP2-targeted therapy will be excluded. Pts will be randomised 1:1 to Arm 1 (Dato-DXd 6 mg/kg IV every 3 weeks [Q3W] + D 1120 mg IV Q3W) or Arm 2 (ICC [paclitaxel, nab-paclitaxel, or gemcitabine + carboplatin] + pembro), or in selected countries, 1:1:1 to Arms 1, 2, or 3 (Dato-DXd alone). Once ∼75 pts have been randomised to Arm 3, it will close and all countries will continue with 1:1 randomisation. Primary endpoint: progression-free survival (PFS) by blinded independent central review per RECIST v1.1. Secondary endpoints: overall survival, objective response rate, duration of response, investigator-assessed PFS, PFS2, clinical benefit rate at 24 weeks, patient-reported outcomes, pharmacokinetics, immunogenicity, safety. Enrolment is planned in 20 countries/regions; recruitment is active in the UK, South Korea and Taiwan at the time of abstract submission. NCT06103864. Medical writing support for the development of this abstract, under the direction of the authors, was provided by Helen Kitchen of Ashfield MedComms (Macclesfield, UK), 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.

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)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Insufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Randomized trial · Consensus signal: Randomized trial
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.408
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.002
Science and technology studies0.0000.000
Scholarly communication0.0000.001
Open science0.0010.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0040.000

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 head0.024
GPT teacher head0.336
Teacher spread0.312 · 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