Tarlatamab Treatment Before and After Surgery in Surgically Resectable Recurrent High-grade Glioma: a Window of Opportunity Study (TARLAGLIA Study)

Sponsor
Vall d'Hebron Institute of Oncology
Study ID
NCT07788677
Phase
PHASE1
Status
Not Yet Recruiting

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Conditions

  • High-Grade Glioma (HGG)

Eligibility Criteria

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

Interventions

  • Tarlatamab — BIOLOGICAL
    Tarlatamab will be administered by intravenous infusion using a step-up dosing regimen. During the neoadjuvant phase, participants will receive 1 mg on Cycle 1 Day 1, followed by 10 mg on Cycle 1 Day 8 and Day 15. Surgery will be performed after a 2-week washout period following the Day 15 dose. Postoperatively, tarlatamab will be restarted approximately 3 weeks after surgery using step-up dosing with 1 mg on Day 1, followed by 10 mg on Day 8 and Day 15. Thereafter, participants will receive tarlatamab 10 mg intravenously every 2 weeks for up to 6 cycles. Each treatment cycle is defined as 4 weeks. Tarlatamab will be administered as a 60-minute intravenous infusion, followed by a slow bolus flush.

Study Details

This is a single-arm, window-of-opportunity clinical study evaluating tarlatamab administered before and after surgery in adult participants with surgically resectable recurrent DLL3-positive high-grade glioma. The study is designed to assess the feasibility and safety of neoadjuvant tarlatamab treatment prior to planned tumor resection, as well as the safety and tolerability of postoperative adjuvant tarlatamab. Eligible participants will have histologically confirmed recurrent high-grade glioma with DLL3-positive tumor expression and will be candidates for neurosurgical resection in whom surgery can be safely delayed to allow neoadjuvant treatment. Participants will receive tarlatamab intravenously using a step-up dosing regimen during the neoadjuvant phase, followed by planned surgical resection after a washout period. After recovery from surgery, participants will restart tarlatamab with step-up dosing and continue adjuvant treatment every 2 weeks for up to 6 cycles. The primary objective is to evaluate the feasibility and safety of neoadjuvant tarlatamab, including the number of participants able to complete the dose-limiting toxicity evaluation period and undergo planned surgery without experiencing a dose-limiting toxicity. Safety assessments will include adverse events graded according to CTCAE v5.0, as well as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome graded according to ASTCT criteria. Secondary objectives include assessment of antitumor activity using RANO and iRANO criteria, progression-free survival, 12-month overall survival, quality of life using EORTC QLQ-C30 and EORTC QLQ-BN20 questionnaires, and the incidence, severity, and type of treatment-emergent adverse events during the adjuvant treatment period.

Key Dates

First listed
Aug 26, 2026
Start date
Oct 1, 2026
Status verified
Jul 2026
Primary completion
May 1, 2029
Completion
May 1, 2029

Study Design

Enrollment
10 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Recurrent high-grade glioma with DDL-3 positive tumor expression, as assessed by IHC.
    Participants with surgically resectable recurrent DLL3-positive high-grade glioma will receive neoadjuvant tarlatamab prior to planned surgery, followed by adjuvant tarlatamab after surgery. In the neoadjuvant phase, tarlatamab will be administered intravenously using a step-up regimen of 1 mg on Cycle 1 Day 1, followed by 10 mg on Days 8 and 15. Surgery will be performed after a 2-week washout period following the Day 15 dose. Approximately 3 weeks after surgery, tarlatamab will be restarted with step-up dosing of 1 mg on Day 1, followed by 10 mg on Days 8 and 15, then continued at 10 mg intravenously every 2 weeks for up to 6 cycles, with each cycle defined as 4 weeks.

Primary Outcome Measure

Number of Participants Completing the DLT Evaluation Period and Undergoing Planned Surgery Without a DLT [ Time Frame: From first neoadjuvant tarlatamab dose through the postoperative safety assessment 7 days after surgery; Cycle 1 is 4 weeks, with dosing on Days 1, 8, and 15 and surgery approximately 2 weeks after Day 15. ]

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