417P SNC115 in patients with relapsed/refractory small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC): Safety, pharmacokinetic, and preliminary efficacy results from a phase I study

Background: DLL3(Delta-like ligand 3) is highly expressed in SCLC, suggesting its potential as a therapeutic target.SNC115 is a CD70-armored DLL3-targeted CAR-T cell.Methods: This single-arm, single-center, open-label phase 1 study will evaluate the preliminary safety and pharmacokinetic of SNC115 in patients with recurrent/refractory SCLC/LCNEC who have failed at least first-line standard therapy.Dose escalation phase follows accelerated titration combined with standard 3+3 design.The planned dose levels are DL1 1.010 5 , DL2 3.010 5 , DL3 1.010 6 , DL4 3.010 6 , and DL5 6.010 6 CAR+ T cells/kg.The Subjects will undergo leukapheresis and lymphodepletion (LD) chemotherapy with a three-day fludarabine plus cyclophosphamide regimen.The primary objective is to assess safety, tolerability and determine the MTD or recommended dose. Results:As of 1 December 2025, 7 patients were all SCLC and treated with SNC115 at DL1 (n=1), DL2 (n=3), DL3 (n=2) and DL4 (n=1).The median age was 53 (range 40-69) years old, and the median number of prior lines of systemic therapy was 3 (range 2-6) lines.5 of them received bridging therapy.CRS occurred in 1 patient each in DL1 and DL4, both cases which were Grade 1 and rapidly resolved following the administration of tocilizumab.Grade 3 or higher hematologic TEAEs included lymphocyte count decreased (7/7), white blood cell count decreased (2/7) and anaemia (1/7), all were related to LD.Only one patient (DL4) experienced Grade 3 or higher non-hematologic TEAEs related to SNC115, including ALT increased (G3), -GT increased (G3) and diarrhea (G3), which resolved rapidly with symptomatic treatment.No cases of DLTs, no SAEs and no ICANS were observed.The ORR of all DLs was 28.6%, and the DCR was 71.4% per RECIST1.1.The expansion of CAR-T cells was detected by qPCR, and peaked at 7 days post-infusion, with Cmax ranging from 69 to 4056 copies/g DNA.Conclusions: SNC115 demonstrated a favorable safety and tolerability profile with no DLTs or ICANS observed, and mild, reversible CRS, warranting further investigation into subsequent higher dose levels.Preliminary signals of efficacy were also identified.Clinical trial identification: NCT06384482.