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

Sponsor
Centre Leon Berard
Study ID
NCT07243470
Phase
PHASE1/PHASE2
Status
Recruiting
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Conditions

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

Eligibility Criteria

Sex
ALL
Age
12 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Tarlatamab — DRUG
    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.
  • Temozolomide (TMZ) — DRUG
    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.

Study Details

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.

Key Dates

Start date
Nov 4, 2025
Status verified
May 2026
Primary completion
Oct 31, 2029
Completion
Oct 31, 2030

Study Design

Enrollment
70 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: Patients with IDH-mutant glioma
    Patients must have histologically confirmed diagnosis of central nervous system (CNS) malignant tumor: IDH-mutant high-grade glioma, other high-grade glioma or other high-grade CNS tumors.
  • Experimental: Patients with other glioma
    Patients must have histologically confirmed diagnosis of central nervous system (CNS) malignant tumor: IDH-mutant high-grade glioma, other high-grade glioma or other high-grade CNS tumors.
  • Experimental: Patients with other CNS tumors
    Patients must have histologically confirmed diagnosis of central nervous system (CNS) malignant tumor: IDH-mutant high-grade glioma, other high-grade glioma or other high-grade CNS tumors.

Primary Outcome Measure

Phase I : Dose limiting toxicities (DLT) assessed as related at least to tarlatamab, occurring during the first 2 cycles of treatment [ Time Frame: From Cycle 1 Day 1 to week 8 ]

Central Contacts

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