eligibility_summary
Adults ≥18 with ES-SCLC: Cohort 1 after 4 cycles carboplatin/etoposide/atezolizumab with ongoing CR/PR/SD, Cohort 2 treatment-naive with measurable, biopsiable disease (pre- and on-treatment biopsies). ECOG ≤1, adequate organ function, contraception/compliance required. Exclude prior B7-H3 or exatecan-ADC, most ICIs (except atezo in C1), recent arterial events, active brain mets, corneal/CV/ILD/pulmonary disease, chronic steroids, recent cancers, transplants, unresolved toxicity, hypersensitivity, active infections (HIV/HBV/HCV), autoimmune disease, recent live vaccine, pregnancy, or factors impairing safety/compliance.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase 1b/2 trial in first-line ES-SCLC tests: 1) Ifinatamab deruxtecan (I-DXd), a B7-H3–targeted antibody-drug conjugate (ADC) carrying a deruxtecan topoisomerase I inhibitor payload, 2) Atezolizumab, an anti–PD-L1 immune checkpoint–blocking monoclonal antibody, 3) Carboplatin, a platinum DNA–crosslinking cytotoxic chemotherapy. Regimens evaluate I-DXd + atezolizumab with or without carboplatin during induction and/or maintenance. Mechanisms: I-DXd binds B7-H3 on tumor cells, is internalized, and releases a topo I inhibitor causing DNA damage and tumor cell death (with potential bystander effect). Atezolizumab blocks PD-L1 to restore T-cell–mediated antitumor immunity. Carboplatin induces DNA crosslinks leading to apoptosis. Targets: B7-H3–expressing SCLC cells, PD-1/PD-L1 immune checkpoint on tumor/immune cells, DNA damage pathways in rapidly proliferating cancer cells.