Phase 1 ML261 DLL3-targeted CAR-T with CARD11–PIK3R3 “armoring” fusion in R/R SCLC/NECs.

This first-in-human, open-label Phase 1 trial (SPECTRAL-1) evaluates ML261, an autologous anti-DLL3 chimeric antigen receptor (CAR) T-cell therapy that also expresses a CARD11–PIK3R3 fusion transgene intended to enhance T-cell activation/signaling and persistence (a potency-enhancement “armoring” strategy). The study’s primary focus is safety/tolerability with pharmacokinetics and preliminary efficacy as key early readouts while establishing dose and feasibility in heavily pretreated patients. Eligible participants include relapsed/refractory, advanced/metastatic, unresectable small cell lung cancer and select neuroendocrine carcinomas (including high-grade neuroendocrine prostate cancer and extrapulmonary NEC) that express DLL3; DLL3 is a lineage-associated surface target enriched in high-grade neuroendocrine tumors, enabling a tumor-directed cellular immunotherapy approach. Moonlight Bio, Inc sponsors the program, positioning ML261 as a solid-tumor CAR-T concept where “armoring” could be commercially differentiating if it improves activity in hostile tumor microenvironments; today’s care for relapsed SCLC or aggressive NEC after platinum-based therapy is largely sequential systemic therapy (e.g., lurbinectedin and/or topotecan for SCLC, clinical trials, and tumor-agnostic options when biomarkers fit), with limited durable benefit—so this tests a targeted cellular therapy beyond conventional chemo.