NCT07243470

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

A Multicenter, Open-label Phase I/II Trial Aiming to Assess the Safety and Clinical Activity of Tarlatamab in Combination With Metronomic Temozolomide in Adolescents and Adults' Patients With High Grade Brain Tumors

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 70 (estimated)
• Sponsor: Centre Leon Berard · Academic / Other
• Sex: All
• Age: 12 Years
• Healthy volunteers: Not accepted

Summary

This clinical trial is a 2-phase trial designed to evaluate the safety of tarlatamab in combination with a fixed dose of metronomic temozolomide in adolescents and adults with CNS tumors (stratified into two age-based cohorts), and to assess the clinical activity of this therapeutic strategy in three parallel, histology-defined cohorts (IDH-mutant glioma, other gliomas, and other CNS tumors). A pre-screening to detect DLL3 expression by IHC on archival tumor sample must be performed before the therapeutic part. Only patients with DLL3 positive tumor on IHC can be enrolled in the therapeutic part. This pre-screening must be optimally performed during the ongoing treatment line i.e. before documented progression to not delay treatment starts at time of progression. Tumor samples (surgery or biopsy specimen) will be sent to a central lab for IHC testing.

Conditions

• Glioma
• CNS Tumor, Adult
• CNS Tumor, Childhood

Interventions

Type	Name	Description
DRUG	Tarlatamab	At the starting dose (DL1): All patients will receive a step dose (1 mg) on C1D1 administered as a 60-minute intravenous (IV) infusion then 10mg at C1D8 and C1D15 of tarlatamab single agent (no temozolomide administered during cycle 1) then tarlatamab at 10mg every D1 \& D15 of each 4-week cycle thereafter in combination with temozolomide from C2D1. At DL-1: a cycle period will be 6 weeks with tarlatamab administration every 3 weeks after Cycle 1.
DRUG	Temozolomide (TMZ)	At DL1 : Metronomic temozolomide will not be administered during the first cycle. It will be administered from the first day of the second cycle, at a dose of 50 mg/m²/day, continuously. At DL-1 : Metronomic temozolomide will not be administered during the first cycle. It will be administered from the first day of the second cycle, at a dose of 50 mg/m²/day, continuously.

Timeline

• Start date: 2025-11-04
• Primary completion: 2029-10-01
• Completion: 2030-10-01
• First posted: 2025-11-24
• Last updated: 2025-11-24

Locations

11 sites across 1 country: France