eligibility_summary
Adults (≥18) with path-confirmed unresectable stage III or metastatic breast cancer that is HER2-low (IHC1+ or 2+/ISH–) and HR+ (≥1%), measurable disease, ECOG 0–1, adequate organs, prior endocrine therapy with progression, no prior chemo/ADC in mBC, provide tumor tissue for central testing. Exclude prior anti‑HER2, MMAE, or PD‑(L)1 in mBC, active CNS mets (unless treated/stable), active HBV/HCV/HIV/COVID, cardiovascular disease, grade ≥2 toxicity/neuropathy, recent RT/therapy, ILD/pneumonitis, autoimmune needing immunosuppression, pregnancy, live vaccines.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Trial NCT06105008 (withdrawn): Randomized Phase 2 in endocrine‑resistant HR+ HER2‑low advanced/metastatic breast cancer comparing disitamab vedotin (RC48‑ADC) + toripalimab vs disitamab vedotin alone. Interventions and mechanisms: • Disitamab vedotin (RC48‑ADC, ADC): HER2‑targeted monoclonal antibody linked to MMAE (vedotin). Binds HER2 on tumor cells (including HER2‑low), internalizes, releases MMAE to inhibit microtubules causing mitotic arrest/apoptosis, Fc‑mediated ADCC may contribute. • Toripalimab (JS001, immune checkpoint inhibitor): anti‑PD‑1 IgG4 monoclonal antibody that blocks PD‑1 on T cells, restoring antitumor T‑cell activity by preventing PD‑1/PD‑L1 signaling. Cells/pathways targeted: • Tumor cells expressing HER2 (IHC 1+ or 2+/ISH‑) → HER2 binding and MMAE‑mediated microtubule disruption. • Immune checkpoint axis → PD‑1 on T cells and PD‑L1/PD‑L2 on tumor/immune cells to enhance cytotoxic T‑cell responses.