eligibility_summary
Adults (≥18) with HR+, HER2‑low (IHC1+ or 2+/ISH–), never HER2+, advanced/metastatic breast cancer, ECOG 0–1, measurable disease, FFPE tumor sample, LVEF ≥50%, adequate organ function, life expectancy ≥12 weeks, progressed on ET±targeted therapy (≤6 months on 1L ET+CDK4/6 and chemo‑appropriate, or after ≥2 ET lines), no prior metastatic chemo (adjuvant/neo ok if >12 mo). Exclude: uncontrolled illness/effusions/ILD, unresolved tox, prior anti‑HER2/exatecan‑ADC/DB‑1303, chemo‑ineligible, substance abuse, staff/institutionalized.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
NCT06018337 tests DB-1303/BNT323 vs investigator’s choice chemotherapy in HR+, HER2-low metastatic breast cancer. Drugs and mechanisms: DB-1303/BNT323 is a HER2-targeted antibody-drug conjugate (ADC). It uses a humanized anti-HER2 mAb with a cleavable linker carrying an exatecan-derived topoisomerase I inhibitor, after binding HER2 on tumor cells, it is internalized and releases the payload to induce DNA damage (Topo I inhibition), S-phase arrest, apoptosis, with a bystander effect. Comparator drugs: capecitabine (oral prodrug of 5-FU, antimetabolite inhibiting thymidylate synthase), paclitaxel and nab-paclitaxel (microtubule-stabilizing taxanes causing mitotic arrest). Cells/pathways targeted: HER2-low breast cancer cells (IHC 1+ or 2+/ISH-), pathways include HER2-mediated uptake, DNA replication/Topo I, pyrimidine synthesis (TS), and microtubule dynamics. Phase 3, randomized, primary endpoint PFS by BICR.