Phase III Study of Tarlatamab Combined with Metronomic Temozolomide for Adolescents and Adults with High-Grade Brain Tumors Expressing DLL3

What this Trial Is About

Researchers are evaluating the safety and clinical activity of combining tarlatamab with a fixed dose of metronomic temozolomide in adolescents and adults who have high-grade central nervous system CNS tumors. The study involves two phases and includes three groups based on tumor histology IDH-mutant glioma, other gliomas, and other CNS tumors. Patients must have tumors expressing DLL3, confirmed by immunohistochemistry IHC on archival tumor samples, which is done before starting the therapeutic part of the trial. Participants receive tarlatamab intravenously starting with a step dose in the first cycle, followed by regular doses every two weeks. Temozolomide is introduced from the second cycle at a continuous daily dose. The trial has two dose levels with different cycle lengths and dosing schedules. The study groups are non-randomized and open-label, with patients classified by tumor type. During the trial, participants will be assessed for dose-limiting toxicities during the first two cycles and clinical activity over 12 weeks. Researchers will monitor tumor response using iRANO criteria and track progression-free survival, overall survival, and adverse events for up to 12 months. Patients must undergo tumor tissue testing and provide informed consent. The study aims to understand the treatments safety and effectiveness in controlling disease progression.

Combination of Tarlatamab and Temozolomide in Patients With Central Nervous System Tumors