eligibility_summary
Eligible: ≥18, consented adults with advanced EGFR‑positive (IHC ≥+) NSCLC, Cohort A treatment‑naïve, Cohort B resistant to 1L regimens containing ICIs (stability >3 mo), ≥1 measurable lesion, ECOG 0–1, survival ≥3 mo, adequate organs. Exclude: driver gene‑positive (EGFR/ALK/ROS1), dual primary malignancies within 5y, active or steroid‑requiring autoimmune disease, systemic infections, CNS mets/disease, unable contraception, prior docetaxel (B), prior ≥G3 irAEs on ICI (B), or per investigator.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
NCT06208033 tests SMET12 + toripalimab with chemotherapy in EGFR-positive advanced NSCLC. Toripalimab: anti-PD-1 IgG4 monoclonal antibody (immune checkpoint inhibitor) blocking PD-1/PD-L1 to restore cytotoxic T-cell activity. SMET12: investigational IV immunotherapy, mechanism/target not specified in the registry (given Q2W the day after toripalimab). Chemotherapy by cohort: adenocarcinoma—pemetrexed (antifolate inhibiting thymidylate synthase/folate pathway) + carboplatin (DNA crosslinking platinum), squamous—paclitaxel (microtubule stabilizer) + cisplatin (DNA crosslinker), ICI-resistant—docetaxel (microtubule stabilizer). Targeted cells/pathways: PD-1 checkpoint on T cells, folate metabolism, DNA replication/repair via platinum, mitotic spindle via taxanes, direct tumor cytotoxicity plus T-cell reactivation.