Abstract 1704: Overcoming resistance in HER2-positive gastric and breast cancers: Efficacy of disitamab vedotin in preclinical models resistant to trastuzumab emtansine and trastuzumab deruxtecan
Bibliographic record
Abstract
BACKGROUND: HER2-positive gastric and breast cancers often develop resistance to the approved antibody-drug conjugates (ADCs) trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd). Disitamab vedotin (DV), a novel anti-HER2 ADC, binds to a distinct epitope on HER2 compared to trastuzumab. This study investigated the therapeutic potential of DV in preclinical models of gastric and breast cancer, including those resistant to T-DM1 and T-DXd and explored whether combining DV with these ADCs could enhance anti-tumor efficacy. METHODS: We evaluated the efficacy of DV, T-DM1, and T-DXd individually and in combination using AlamarBlue cell proliferation assays in HER2-positive gastric and breast cancer cell lines, including models resistant to T-DM1 and T-DXd. We assessed the in vivo efficacy of DV in SCID mouse xenograft models of gastric and breast cancer that had progressed on T-DM1 and/or T-DXd. We examined dual combinations of the three ADCs in xenograft models to evaluate potential synergistic effects. RESULTS: DV demonstrated significant anti-tumor activity in both in vitro and in vivo models, including cell lines and xenografts that were resistant to T-DM1 and T-DXd. In xenograft models, DV effectively inhibited tumor growth in cancers that had progressed following treatment with T-DM1 and/or T-DXd. Notably, combining DV with either T-DM1 or T-DXd resulted in superior anti-tumor effects compared to the use of single agents alone, both in cell culture and in xenograft studies. CONCLUSIONS: This study highlights the effectiveness of DV in overcoming resistance to T-DM1 and T-DXd in preclinical models of HER2-positive gastric and breast cancer. The combination of DV with these ADCs demonstrated enhanced efficacy, underscoring the potential of dual ADC strategies to improve outcomes in HER2-positive cancers. Citation Format: Negar Pourjamal, Vadim Le Joncour, György Vereb, Cilla Honkamaki, Jorma Isola, Jeffrey V Leyton, Pirjo Laakkonen, Heikki Joensuu, Mark Barok. Overcoming resistance in HER2-positive gastric and breast cancers: Efficacy of disitamab vedotin in preclinical models resistant to trastuzumab emtansine and trastuzumab deruxtecan [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1704.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 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 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".