eligibility_summary
Inclusion: RECIST-measurable, ECOG 0–1, advanced breast or gastric/GEJ post-SOC. Cohorts—A: HER2‑low breast, ≤3 chemo, prior T‑DXd/topo‑I, HR+ endocrine‑refractory (with CDK4/6), HR−/PD‑L1+ needs prior pembro. B: HER2+ breast, prior trastuzumab/pertuzumab/taxane, post T‑DXd, ≤3. C: HER2‑low gastric/GEJ, prior platinum/5‑FU/taxane, ≤2, PD‑1 ok, no prior HER2, FFPE needed. D: HER2+ gastric/GEJ, prior trastuzumab+FP/platinum, T‑DXd/PD‑1 ok, ≤2. Exclude: hypersensitivity, prior MMAE‑ADC/tucatinib, active CNS/LM, recent Tx <4w, malignancy <3y, cannot swallow/absorb.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Study tests two HER2-targeted agents in LA/metastatic breast and gastric/GEJ cancers (HER2-low and HER2+): 1) Disitamab vedotin (RC48): an IV antibody–drug conjugate (monoclonal anti-HER2 antibody linked to MMAE, a microtubule inhibitor). Mechanism: binds HER2 on tumor cells, internalizes, releases MMAE to disrupt microtubules, causing G2/M arrest, apoptosis, and potential bystander killing. 2) Tucatinib (TUKYSA, ONT-380): an oral, highly selective small-molecule HER2 tyrosine kinase inhibitor. Mechanism: inhibits HER2 (ERBB2) kinase activity with minimal EGFR inhibition, suppressing downstream MAPK and PI3K–AKT signaling. Targets: HER2-expressing epithelial tumor cells (breast, gastric/GEJ). Pathways: HER2/ERBB2 signaling cascade and microtubule dynamics. Goal: assess safety/efficacy and optimize DV dose in combination with tucatinib.