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

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