eligibility_summary
Adults ≥18, measurable disease, ECOG 0–1. A: unresectable/metastatic breast, if HR+, endocrine‑refractory, 1–2 prior chemo, HER2‑low (IHC1+ or 2+/ISH−), never HER2+. B: unresectable/metastatic gastric/GEJ or progressed on trastuzumab. C: stage IIIB–IV nonsq NSCLC, required prior therapy per AGA status. Exclude: prior EZH inhibitors, cardiopulmonary, CNS mets/lepto, CYP3A inducers, steroids >10 mg, mAb hypersensitivity, infection, pregnancy. Sub‑excls: A/B exatecan topo‑I ADCs, A anti‑HER2, C topo‑I or TROP2.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase 1b, open-label study testing: 1) Valemetostat tosylate (DS-3201b) – an oral small-molecule dual EZH1/2 histone methyltransferase inhibitor that lowers PRC2-mediated H3K27me3 to reprogram tumor gene expression, 2) DXd antibody-drug conjugates: trastuzumab deruxtecan (T-DXd, HER2-targeted ADC) and datopotamab deruxtecan (Dato-DXd, TROP2-targeted ADC). ADCs bind HER2 or TROP2 on tumor cells, internalize, and release a cleavable deruxtecan topoisomerase I inhibitor payload, causing DNA damage and cytotoxicity with a bystander effect. Targets: EZH1/2-driven epigenetic silencing (PRC2/H3K27me3) in tumor cells, HER2-expressing cells (HER2+ gastric/GEJ, HER2-low breast cancer), TROP2-expressing cells (non-squamous NSCLC), and nuclear topoisomerase I.