eligibility_summary
Eligible: women 18–70 with path‑confirmed advanced breast cancer, failed 1st‑line, ≤3 prior MBC chemo, ECOG ≤2, ≥3‑mo survival, measurable or bone‑only disease, LVEF ≥50%, toxicities ≤G1, AST/ALT ≤2.5×ULN, bili ≤1.5×ULN, adequate marrow/renal (WBC ≥3.0, ANC ≥1.5, Plt ≥100, Hgb ≥90, Cr ≤1.5×ULN), willing for SG or T‑DXd. Exclude: poor absorption, serious heart disease, drug allergy, recent therapy/trial, pregnancy/no contraception, investigator‑judged risk.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
NCT06328387 tests adding hydroxychloroquine (HCQ) to antibody–drug conjugates (ADCs) in advanced breast cancer. Arms: sacituzumab govitecan (SG) vs SG+HCQ, trastuzumab deruxtecan (T-DXd) vs T-DXd+HCQ. Drugs/mechanisms: • SG: ADC (anti–TROP-2 mAb) delivering SN-38/govitecan, a topoisomerase I inhibitor, internalized via TROP-2, linker cleavage releases cytotoxic payload (bystander effect possible). • T-DXd: ADC (anti-HER2 mAb) delivering DXd, a membrane-permeable topoisomerase I inhibitor via cathepsin-cleavable linker (bystander effect). • HCQ: small-molecule autophagy inhibitor (lysosomotropic, raises lysosomal pH and blocks autophagosome–lysosome fusion), potentially enhancing ADC efficacy/resistance reversal. Targets/pathways: HER2+ or TROP-2+ tumor cells, receptor-mediated endocytosis, lysosomal processing, macroautophagy/lysosome pathway, topoisomerase I–mediated DNA damage.