Preliminary safety and efficacy of tarlatamab in previously treated medullary thyroid carcinoma

Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor with high rates of delta-like ligand 3 (DLL3) expression. MTC has limited treatment options after failure of kinase inhibition. DLL-targeting therapies such as tarlatamab may be effective treatment for MTC. A pilot study at Massachusetts General Hospital (Boston) evaluated tarlatamab in four patients with MTC after progression on all established therapies. Patients were treated using the step-up dosing described in patients with small cell lung cancer. Efficacy was measured using RECIST v1.1, as well as changes in calcitonin and CEA. Tarlatamab showed antitumor activity in all four patients. All four patients experienced at least one grade ≥ 3 TRAE. Severe TRAEs include grade 5 colon perforation, grade 4 CRS, grade 4 ICANS, and grade 3 leukopenia, neutropenia, hypophosphatemia, and anorexia. The grade 4 CRS and grade 4 ICANS were refractory to standard treatments. The authors conclude that tarlatamab showed encouraging antitumor activity in patients with MTC. However, safety data from these initial patients raise concern that the step-up dosing established for patients with SCLC may not be optimal for patients with MTC.