eligibility_summary
Adults (>=18) with unresectable metastatic/recurrent HER2+ breast cancer (IHC 3+ or 2+/FISH+), tumor tissue available, >=1 evaluable lesion, ECOG 0-1, adequate labs within 14 days. Prior therapy must include >=1 line trastuzumab + taxane. Contraception if fertile. Exclude: prior ADCs or CDK4/6 inhibitors, anti-HER2 drugs other than trastuzumab, pertuzumab, or TKIs, CNS mets, recent cancers, major organ dysfunction, investigational drug <28 days, allergy to CDK4/6 inhibitors, pregnancy.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase II single-arm study in HER2-positive unresectable/metastatic breast cancer testing T-DM1 plus ribociclib (± endocrine therapy if ER+). Drugs/mechanisms: • Trastuzumab emtansine (T-DM1): antibody-drug conjugate (ADC). Trastuzumab targets HER2 on tumor cells, inhibits HER2 signaling and mediates ADCC, internalization releases DM1, a maytansinoid microtubule inhibitor, causing mitotic arrest and cytotoxicity. • Ribociclib: oral small-molecule CDK4/6 inhibitor that blocks cyclin D–CDK4/6, reduces RB phosphorylation, and induces G1 cell-cycle arrest. Targets and pathways: HER2-overexpressing breast cancer cells, HER2/ErbB2 signaling, microtubules, and the CDK4/6–RB–E2F cell-cycle axis, in ER+ patients, estrogen receptor signaling is also targeted via concurrent endocrine therapy.