A phase II single-arm, open-label trial of T-DM1 (ado-trastuzumab emtansine) and neratinib for HER2-positive breast cancer with molecular residual disease (KAN-HER2 MRD).
Bibliographic record
Abstract
TPS620 Background: HER2-positive breast cancer is a biologically and clinically aggressive subtype that has historically been associated with poor outcomes, but for which there are now multiple effective targeted therapies. Patients who have residual disease following standard neoadjuvant therapy have an elevated risk of metastatic recurrence. In addition, the detection of circulating tumor DNA (ctDNA) in the adjuvant period is strongly associated with relapse and can further stratify patients with residual disease. The ctDNA-based detection of molecular residual disease (MRD) is an emerging strategy to identify patients for treatment intensification, and may enable the development of novel curative treatment strategies for “recurrence interception”. Preclinical and clinical evidence support the investigation of neratinib, an irreversible inhibitor of the HER2 tyrosine kinase, in combination with standard T-DM1 in the adjuvant setting for patients with HER2-positive breast cancer and evidence of MRD. Methods: KAN-HER2 MRD is a multicentre, investigator-initiated, open label, single arm phase II trial to evaluate the addition of neratinib to standard T-DM1 in patients with detected MRD. Participants with HER2-positive breast cancer and residual disease following neoadjuvant therapy are pre-screened (Part A) for MRD using a tumor-informed assay (NeoGenomics RaDaR). Those with ctDNA detected following 2-6 cycles of adjuvant T-DM1 will proceed to the interventional phase (Part B) where neratinib is added to standard T-DM1 at the previously-determined recommended phase 2 combination dose of 160 mg/day, in continuous cycles. The primary endpoint is the rate of ctDNA clearance at 12 weeks after treatment initiation (ctDNAwk12); the study is designed with a 2-stage approach and has sufficient power to detect a clearance rate of 40%. Secondary endpoints include MRD rates and their clinical correlates, invasive disease free survival (iDFS), and safety. Bio-specimens including diagnostic biopsies, residual disease, and peripheral blood are being collected from all participants for additional correlative studies. Enrolment in Part A was initiated at the first trial site (Princess Margaret Cancer Centre) in December 2022. KAN-HER2 represents the first reported MRD-directed interception trial for HER2-positive breast cancer. Clinical trial information: NCT05388149 .
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.002 | 0.003 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.003 | 0.006 |
| Insufficient payload (model declined to judge) | 0.008 | 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".