eligibility_summary
Adults (≥18) with unresectable/metastatic/recurrent, histology‑confirmed BTC after failure of gem/platinum/5‑FU and PD‑1/PD‑L1, measurable disease (outside/progressing if prior local therapy), ECOG ≤2, life expectancy >3 mo, adequate organ function. Tissue for PD‑L1/CTLA‑4/CLDN18.2 (stage 2 requires CLDN18.2 ≥40%). Controlled HBV/HCV allowed. Exclude prior CTLA‑4/anti‑CLDN18.2, recent major procedures, active autoimmune, serious cardiac/CVA/bleeding/thromboembolism/ILD/pneumonitis/HIV, GI perforation, other active cancers.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Trial NCT05994001 tests: 1) Candonilimab (AK104) – a bispecific monoclonal antibody immune checkpoint inhibitor targeting PD‑1 and CTLA‑4. Mechanism: blocks PD‑1/PD‑L1 and CTLA‑4 co‑inhibitory signals to reinvigorate antitumor T‑cell activity, enhancing CD8+ effector function and reducing Treg-mediated suppression. 2) LM‑302 – a Claudin18.2‑targeting antibody–drug conjugate (ADC). Mechanism: binds CLDN18.2 on tumor cells, is internalized, and releases a microtubule‑disrupting cytotoxic payload causing tumor cell death, may also engage immune effector functions via the antibody. Targets/cell pathways: PD‑1 and CTLA‑4 pathways on T cells (exhausted PD‑1+ effectors and Tregs), CLDN18.2‑expressing biliary tract cancer cells (tight‑junction protein) with downstream microtubule disruption. Design: Phase 1/2, China, monotherapy candonilimab, monotherapy LM‑302, or their combination after failure of SOC and prior PD‑(L)1 therapy.