TROPION-Breast05: a randomized phase III study of Dato-DXd with or without durvalumab versus chemotherapy plus pembrolizumab in patients with PD-L1-high locally recurrent inoperable or metastatic triple-negative breast cancer
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.
Bibliographic record
Abstract
Background: Standard of care (SoC) for patients with advanced triple-negative breast cancer (TNBC) whose tumors express PD-L1 (combined positive score ⩾ 10) is chemotherapy plus anti-PD-(L)1 inhibitors; however, prognosis and survival for most patients is poor. Datopotamab deruxtecan (Dato-DXd), a novel antibody-drug conjugate comprising a humanized anti-TROP2 IgG1 monoclonal antibody conjugated to a potent topoisomerase I inhibitor payload via a plasma-stable, cleavable, tetrapeptide-based linker, has shown preliminary activity as mono or combination therapy in advanced/metastatic TNBC. Objectives: TROPION-Breast05 is an ongoing randomized, open-label, multicenter phase III study. The primary objective is to demonstrate the superiority of Dato-DXd in combination with durvalumab (an anti-PD-L1 antibody) versus SoC treatment in patients with PD-L1-high locally recurrent inoperable or metastatic TNBC. Methods and design: Patients (⩾18 years) will be randomized 1:1 to receive Dato-DXd (6 mg/kg intravenously (IV) every 3 weeks (Q3W)) plus durvalumab (1120 mg IV Q3W) or investigator's choice of chemotherapy (ICC; paclitaxel, nab-paclitaxel, or gemcitabine plus carboplatin) plus pembrolizumab (200 mg IV Q3W). In selected countries, patients will also be randomized (1:1:1) to a third arm of Dato-DXd monotherapy. The primary study endpoint is progression-free survival (PFS) per blinded independent central review (Dato-DXd plus durvalumab arm vs ICC plus pembrolizumab arm). Overall survival is a key secondary endpoint; other secondary endpoints include PFS (investigator-assessed), objective response rate, duration of response, clinical benefit rate at Week 24 (all assessed in the Dato-DXd plus durvalumab arm vs ICC plus pembrolizumab arm), patient-reported outcomes, and safety. Ethics: The study is approved by independent ethics committees or institutional review boards at each study site. All patients will provide written informed consent. Discussion: TROPION-Breast05 will assess the potential role of Dato-DXd with or without durvalumab in patients with PD-L1-high advanced or metastatic TNBC. The findings of this trial could lead to a new treatment option for these patients. Trial registration: ClinicalTrials.gov identifier: NCT06103864 (Date of registration: 27 October 2023).
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.002 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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 it