Safety, pharmacokinetic, and preliminary efficacy of SNC115 in patients with relapsed/refractory small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC): A phase 1 study.

Abstract

8106 Background: SCLC and LCNEC are characterized by aggressive clinical courses and limited therapeutic options following progression on platinum-based chemotherapy. DLL3(Delta-like ligand 3) is highly expressed and selectively on the surface of these high-grade neuroendocrine tumors, making it an ideal therapeutic target. SNC115 is a novel CAR-T cell armored with CD70 to target DLL3-expressing cells. Methods: This phase 1, open-label study utilized an accelerated titration design followed by a standard 3+3 escalation to evaluate the safety, tolerability, and pharmacokinetics of SNC115 in patients (pts) with R/R SCLC or LCNEC who progressed after ≥1 line of standard therapy. Following leukapheresis and a 3-day lymphodepletion regimen (fludarabine/cyclophosphamide), pts received a single infusion of SNC115 at one of five planned dose levels (DL): 1.0×10^5 (DL1), 3.0×10^5 (DL2), 1.0×10^6 (DL3), 3.0×10^6 (DL4), and 6.0×10^6 (DL5) CAR + T cells/kg. The primary endpoints were the determination of the maximum tolerated dose (MTD) and the recommended dose (RD). Results: As of 23 January 2026, 8 pts with R/R SCLC were treated across four DLs: DL1 (n = 1), DL2 (n = 3), DL3 (n = 2) and DL4 (n = 2). Median age was 53.5 (range 40-69) years, with a median of three prior therapy lines (range 2-6). 6 pts received bridging therapy. SNC115 demonstrated a manageable safety profile. CRS occurred in 3 pts (DL1: 1pt, DL4: 2pts), all Grade 1 or 2 and resolved with tocilizumab/corticosteroids. Grade ≥3 hematologic TEAEs included lymphocyte count decreased (8/8), white blood cell count decreased (2/8) and anaemia (1/8), all attributed to LD. Only one patient (DL4) experienced Grade ≥3 non-hematologic TEAEs related to SNC115, including alanine aminotransferase increased (G3), Gamma-glutamyltransferase increased (G3) and diarrhea (G3), which resolved with symptomatic care. No DLTs, SAEs or ICANS were reported. Among evaluable pts (n = 8), the ORR and DCR were 37.5% and 75%, respectively. All patients (n = 2) in the higher-dose level (DL4) achieved PR. CAR-T cells expansion peaked at a median of 7 days post-infusion, with Cmax ranging from 68.77 to 4359.89 copies/µg DNA. Conclusions: SNC115 demonstrated a manageable safety profile and encouraging preliminary antitumor activity in heavily pretreated pts with SCLC. The absence of DLTs and ICANS, combined with low-grade transient CRS, supports continued dose escalation. These early efficacy signals suggest that SNC115 may provide a novel therapeutic avenue for R/R SCLC. Clinical trial information: NCT06384482 .