A Study to Evaluate the Safety and Efficacy of L19TNF With Alkylating Chemotherapy for Patients With Recurrent IDH-mutant Astrocytoma or Oligodendroglioma
IMAGLIO
A Phase II Study to Evaluate the Safety and Efficacy of L19TNF With Alkylating Chemotherapy for Patients With Recurrent IDH-mutant Astrocytoma or Oligodendroglioma
1 other identifier
interventional
52
0 countries
N/A
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Jan 2026
Typical duration for phase_2
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 30, 2025
CompletedFirst Posted
Study publicly available on registry
August 13, 2025
CompletedStudy Start
First participant enrolled
January 30, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 30, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
January 30, 2029
August 13, 2025
July 1, 2025
3 years
July 30, 2025
August 6, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
Progression-free survival (PFS)
Progression-free survival (PFS) in according to RECIST v.1.1. The duration is defined beginning from randomization to progression or death from any cause.
The PFS rate will be assessed at 12 months (PFS-12) in IDH mutant astrocytoma and in oligodendroglioma.
Study Arms (7)
1: perioperative cohort of patients with recurrent astrocytoma or oligodendroglioma
EXPERIMENTALpatients will be treated with 1 cycle (D1, D3 and D5) L19TNF before resection and 4 weeks after surgery
2A:L19TNF Monotherapy for patients with recurrent oligodendroglioma
EXPERIMENTALpatients with IDH-mutant oligodendroglioma, WHO Grade 2 or 3 at first progression after radiotherapy and one line of systemic chemotherapy, are treated with up to 6 cycles of 6 weeks with L19TNF
2B1: L19TNF plus TMZ for patients with recurrent oligodendroglioma
EXPERIMENTALpatients with IDH-mutant oligodendroglioma, WHO Grade 2 or 3 at first progression after radiotherapy and one line of systemic CCNU-based chemotherapy, are treated with L19TNF and temozolomide chemotherapy TMZ
2B2: L19TNF plus CCNU for patients with recurrent oligodendroglioma
EXPERIMENTALpatients with IDH-mutant oligodendroglioma, WHO Grade 2 or 3 at first progression after radiotherapy and one line of systemic temozolomide chemotherapy, are treated with L19TNF and CCNU
3A: L19TNF monotherapy for patients with recurrent astrocytoma
EXPERIMENTALpatients with IDH-mutant astrocytoma, WHO Grade 2, 3 or 4 at first progression after radiotherapy and one line of systemic chemotherapy, are treated with L19TNF
3B1: L19TNF plus TMZ for patients with recurrent astrocytoma
EXPERIMENTALpatients with IDH-mutant astrocytoma, WHO Grade 2, 3 or 4 at first progression after radiotherapy and one line of systemic CCNU-based chemotherapy, are treated with L19TNF and temozolomide chemotherapy TMZ
3B2: L19TNF plus CCNU for patients with recurrent astrocytoma
EXPERIMENTALpatients with IDH-mutant astrocytoma, WHO Grade 2, 3 and 4 at first progression after radiotherapy and one line of systemic chemotherapy including temozolomide, are treated with L19TNFand CCNU
Interventions
1 cycle of TNF before resection and 6 cycles after surgery
6 cycles of 28 days with L19TNF and TMZ
6 cycles of 6 weeks of L19TNF and CCNU every 6 weeks
6 cycles of 6 weeks with L19TNF
6 cycles of 28 days with L19TNF (D1, D3, D5) and temozolomide chemotherapy TMZ (D1-5).
6 cycles of 6 weeks of L19TNF (D1, D3, D5, D22, D24 and D26) and CCNU (D1) every 6 weeks
6 cycles of 6 weeks with L19TNF
Eligibility Criteria
You may qualify if:
- Age ≥18
- IDH-mutant glioma (according to WHO 2021 classification) at first recurrence or progression after alkylating chemotherapy:
- COHORT 1: Grade ≥2 oligodendroglioma or astrocytoma with planned resection, tumor tissue from prior resection must be available
- COHORT 2A: Grade ≥2 oligodendroglioma
- COHORT 2B1: Grade ≥2 oligodendroglioma previously treated with lomustine as monotherapy or in combination
- COHORT 2B2: Grade ≥2 oligodendroglioma previously treated with temozolomide as monotherapy or in combination
- COHORT 3A: Grade ≥2 astrocytoma
- COHORT 3B1: Grade ≥2 astrocytoma previously treated with lomustine as monotherapy or in combination
- COHORT 3B2: Grade ≥2 astrocytoma previously treated with temozolomide as monotherapy or in combination
- Measurable disease according to RANO 2.0 criteria.
- Documented IDH1 and/or IDH2 gene mutations detected by immunochemistry or sequencing.
- Karnofsky Performance Status (KPS) ≥ 70%.
- Life expectancy ≥ 3 months.
- Documented negative test for HIV-HBV-HCV. For HBV serology, the determination of HBsAg and anti-HBcAg Ab is required. In patients with serology documenting previous exposure to HBV, negative serum HBV-DNA is required. For HCV, HCV-RNA or HCV antibody test is required. Subjects with a positive test for HCV antibody but no detection of HCV-RNA indicating no current infection are eligible.
- Female patients: female patients must be either documented not Women Of Childbearing Potential (WOCBP)\* or must have a negative pregnancy test within 14 days of starting treatment. Additionally WOCBP must agree to use, from the screening to 6 months following the last study drug administration, highly effective contraception methods, as defined by the "Recommendations for contraception and pregnancy testing in clinical trials" issued by the Head of Medicine Agencies' Clinical Trial Facilitation Group (www.hma.eu/ctfg.html) and which include, for instance, progesterone-only or combined (estrogen- and progesterone-containing) hormonal contraception associated with inhibition of ovulation, intrauterine devices, intrauterine hormone-releasing systems, bilateral tubal occlusion or vasectomized partner.
- +3 more criteria
You may not qualify if:
- Any therapy for recurrence/progression after alkylating chemotherapy, except resection.
- Therapy for glioma within 4 weeks of start of study treatment.
- Surgical resection of glioma within 4 weeks of start of study treatment.
- Stereotactic biopsy of glioma within 2 weeks of start of study treatment.
- Inability to undergo contrast-enhanced MRI.
- Known history of allergy to TNF or lomustine or temozolomide, any excipient in the study medication or any other intravenously administered human proteins/peptides/antibodies.
- Absolute neutrophil count (ANC) \< 1.5 x 10\^9/L; platelets \< 100 x 10\^9/L or hemoglobin (Hb) \< 9.0 g/dl.
- Chronically impaired renal function as indicated by creatinine clearance \< 60 mL/min/1.73m2 or for patients older than 65 years without albuminuria or proteinuria, creatinine clearance \< 45 mL/min/1.73m2.
- Inadequate liver function (ALT, AST, ALP ≥ 2.5 x ULN or total bilirubin ≥ 1.5 x ULN).
- INR \> 1.5 ULN.
- Any severe concomitant condition, which makes it undesirable for the patient to participate in the study or which could jeopardize compliance with the protocol, in the opinion of the investigator.
- Active or history of autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent, in the judgement of the investigator.
- History within the last year of cerebrovascular disease and/or acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris.
- Heart insufficiency (\> Grade II, New York Heart Association (NYHA) criteria).
- Clinically significant cardiac arrhythmias or requiring permanent medication.
- +18 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Philogen S.p.A.lead
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 30, 2025
First Posted
August 13, 2025
Study Start
January 30, 2026
Primary Completion (Estimated)
January 30, 2029
Study Completion (Estimated)
January 30, 2029
Last Updated
August 13, 2025
Record last verified: 2025-07
Data Sharing
- IPD Sharing
- Will not share