A case of Large Cell Neuroendocrine Carcinoma (LCNEC) treated with tarlatamab

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare, high-grade, neuroendocrine carcinoma with an aggressive clinical course, and there are few treatment options for relapsed and refractory cases. Tarlatamab, a first-in-class, bispecific T-cell engager targeting delta-like ligand 3 (DLL3) and CD3, holds promise as a therapeutic option for previously treated cases of small-cell lung cancer, but clinical data on LCNEC are exiguous. We report herein a 69-year-old, male patient. He underwent a left upper lobe partial resection for stage pT1bN0M0 LCNEC. Three years later, a recurrence with left pleural thickening, multiple liver metastases, and a marked elevation of pro-gastrin-releasing peptide developed. The patient had received five lines of systemic therapy over 2.5 years. Comprehensive genomic profiling revealed a high tumor mutational burden but no actionable targets. With approval from the institutional ethics committee, tarlatamab therapy was begun as sixth-line therapy. The patient experienced manageable grade 1 cytokine release syndrome. After two cycles, computed tomography demonstrated a partial response with a 40% reduction in the sum of target lesion diameters (130 mm to 78 mm), and the pro-gastrin-releasing peptide level decreased from 1610 ng/mL to 49.7 ng/mL. The patient has received nine cycles of tarlatamab over eight months, and the response has persisted during this period without any serious adverse events. The findings of the present case suggest that tarlatamab has the potential to induce a meaningful and durable response in pretreated LCNEC and support further clinical evaluation of DLL3-targeted, T-cell-engaging therapy for this disease.