eligibility_summary
Adults 18–70, ECOG 0–2, ≥3‑mo survival, unresectable/rec/metastatic TNBC after taxanes, MRI‑proven brain mets with ≥1 untreated ≥1 cm lesion, stable steroids, adequate organ function. Cohort A: no prior CNS RT (≥2 wks post‑op ok). Cohort B: progression after WBRT/SRT. Exclude leptomeningeal dz, uncontrolled effusions, recent therapy, prior anti‑VEGF/checkpoint or TROP2 ADC, serious cardiac dz, infection/immunodef or HBV (no antivirals), live vaccines, active autoimmune, pregnancy.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Interventions: Ivonescimab (AK112/SMT112), a bispecific monoclonal antibody targeting PD-1 and VEGF-A, combined with a TROP2-directed antibody–drug conjugate (ADC), such as sacituzumab govitecan (SN-38 payload). Mechanisms: Ivonescimab blocks PD-1 to restore antitumor T-cell activity and neutralizes VEGF-A to inhibit angiogenesis, normalize tumor vasculature, and reduce immunosuppressive signaling. The TROP2 ADC binds TROP2 on tumor cells, is internalized, and releases the topoisomerase I inhibitor SN-38 to cause DNA damage–induced cell death (with potential bystander effect). Targets/cells/pathways: PD-1 on activated T cells, VEGF-A/VEGFR axis on endothelial cells and tumor microenvironment, TROP2 on TNBC tumor cells (including brain metastases). Phase II, single-arm in TNBC with brain metastases.