eligibility_summary
Adults (≥18) with unresectable/metastatic breast cancer, ECOG 0–1, measurable disease, biopsy-accessible tumor, adequate organs. Progressed on/≤2 mo after T-DXd. HER2+: prior trastuzumab+taxane (±T-DM1/pertuzumab). HER2-low: taxane. HR+: ET+CDK4/6 unless now HR–. gBRCA: prior PARPi. Exclude: resectable disease, ILD/pulmonary compromise, active/symptomatic brain/leptomeningeal mets, chronic steroids >10 mg, major cardiac disease, active HBV/HCV, pregnancy, uncontrolled HIV, unresolved ≥G2 tox, prior anti-HER3 Ab, inadequate washout, severe hypersensitivity, recent other cancer. Contraception/consent required.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
NCT06298084 (ICARUS-BREAST02) is a phase 1b/2 study in inoperable advanced breast cancer after progression on trastuzumab deruxtecan. Interventions: Patritumab deruxtecan (HER3-DXd, U3-1402), an antibody–drug conjugate (anti-HER3 monoclonal antibody linked to the topoisomerase I inhibitor DXd), tested as monotherapy and combined with olaparib (Lynparza), an oral small-molecule PARP1/2 inhibitor. Mechanisms: HER3-DXd binds HER3 (ERBB3) on tumor cells, internalizes, and releases DXd to cause DNA damage (Topo I inhibition, potential bystander effect). Olaparib blocks PARP-mediated base-excision repair, increasing DNA damage and synthetic lethality. Targets: HER3-expressing breast cancer cells (HER2-low and HER2-positive), HER3→PI3K/AKT signaling, and DNA damage response/repair pathways (PARP, homologous recombination). Objectives: safety/RP2D and efficacy (ORR).