A Novel Approach to Targeting DLL3 with Tarlatamab in a Patient with Medullary Thyroid Carcinoma after Progression on Selpercatinib

BACKGROUND: altered medullary thyroid carcinoma (MTC) face a poor prognosis. Tarlatamab-a Delta-like ligand 3-targeted bispecific T-cell engager-is a promising therapeutic option for patients with MTC, but a prior case series raised safety concerns in this population. METHODS: altered MTC who progressed on selpercatinib received tarlatamab using a three-step step-up dosing regimen with modified protocols for monitoring and managing cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). RESULTS: This patient experienced grade 2 CRS and grade 2 ICANS after cycle 1, day 1. He did not experience any grade ≥3 treatment-related adverse events. The patient had rapid improvement of the disease-associated symptoms. After 8 weeks of treatment, the patient experienced a biochemical and radiographic complete response that is ongoing. CONCLUSIONS: A modified dosing and monitoring protocol may improve the safety of tarlatamab in patients with MTC while maintaining efficacy. Further research is needed to evaluate the role of tarlatamab in MTC.