NCT07120984

A Study to Evaluate the Safety and Efficacy of L19TNF With Alkylating Chemotherapy for Patients With Recurrent IDH-mutant Astrocytoma or Oligodendroglioma

A Phase II Study to Evaluate the Safety and Efficacy of L19TNF With Alkylating Chemotherapy for Patients With Recurrent IDH-mutant Astrocytoma or Oligodendroglioma

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 52 (estimated)
• Sponsor: Philogen S.p.A. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to explore the safety and efficacy of the antibody-cytokine fusion protein L19TNF alone or in combination with alkylating chemotherapy in patients with recurrent IDH mutant glioma.

Detailed description

This protocol describes an open label, multi-centric phase 2 study and patients will be treated with L19TNF at 13µg/kg as monotherapy or in combination with alkylating chemotherapy (Lomustine or Temozolamide) in different cohorts: * COHORT 1: L19TNF monotherapy in perioperative cohort of patients with recurrent astrocytoma or oligodendroglioma, * COHORT 2A: L19TNF Monotherapy for patients with recurrent oligodendroglioma, * COHORT 2B1: L19TNF plus TMZ for patients with recurrent oligodendroglioma, * COHORT 2B2: L9TNF plus CCNU for patients with recurrent oligodendroglioma, * COHORT 3A: L19TNF Monotherpay for patients with recurrent astrocytoma, * COHORT 3B1: L19TNF plus TMZ for patients with recurrent astrocytoma, * COHORT 3B2: L19TNF plus CCNU for patients with recurrent astrocytoma. Eligibility criteria in this trial are: * Age ≥18 * IDH-mutant glioma at first recurrence or progression after alkylating chemotherapy: * COHORT 1: Grade ≥2 oligodendroglioma or astrocytoma with planned resection * COHORT 2A, 2B1, 2B2: Grade ≥2 oligodendroglioma * COHORT 3A, 3B1, 3B2: Grade ≥2 astrocytoma * No therapy for first recurrence or progression after alkylating chemotherapy, except resection. * Patients must have measurable disease according to RANO 2.0 * Karnofsky Performance Status (KPS) ≥ 70%. The primary endpoint of the study is the Progression Free Survival Rate at 12 months (PFS-12). The following secondary endpoints are considered: * Progression-free survival (PFS) * Overall response rate (ORR) * Disease control rate * Duration of response (DoR) * Overall survival (OS) * Safety and tolerability: adverse event (AE), serious AE (SAE), Drug-induced liver injury (DILI), physical examinations, echocardiography, ECG and standard laboratory parameters (hematology, biochemistry liver and urine analysis) * Human anti-factor antibodies (HAFA) * popPK

Conditions

• Glioma

Interventions

Type	Name	Description
BIOLOGICAL	L19TNF	1 cycle of TNF before resection and 6 cycles after surgery
BIOLOGICAL	L19TNF and TMZ	6 cycles of 28 days with L19TNF and TMZ
BIOLOGICAL	L19TNF and CCNU	6 cycles of 6 weeks of L19TNF and CCNU every 6 weeks
BIOLOGICAL	L19TNF monotherapy	6 cycles of 6 weeks with L19TNF
BIOLOGICAL	L19TNF and TMZ in recurrent astrocytoma	6 cycles of 28 days with L19TNF (D1, D3, D5) and temozolomide chemotherapy TMZ (D1-5).
BIOLOGICAL	L19TNF and CCNU in recurrent astrocytoma	6 cycles of 6 weeks of L19TNF (D1, D3, D5, D22, D24 and D26) and CCNU (D1) every 6 weeks
BIOLOGICAL	L19TNF monothery in recurrent oligodendroglioma	6 cycles of 6 weeks with L19TNF

Timeline

• Start date: 2026-01-30
• Primary completion: 2029-01-30
• Completion: 2029-01-30
• First posted: 2025-08-13
• Last updated: 2025-08-13