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Combining L19TNF and Lomustine for Glioblastoma Treatment

A Dose Optimization Study for L19TNF in Combination With Lomustine in Patients With Glioblastoma at Progression or Recurrence

Phase 2 Interventional Philogen S.p.A. · NCT06336291

This study is testing if a new combination of L19TNF and lomustine can help people with glioblastoma whose cancer has come back or gotten worse.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment90 (estimated)
Ages18 Years and up
SexAll
SponsorPhilogen S.p.A. Industry-sponsored
Drugs / interventionsBevacizumab, chemotherapy, immunotherapy, radiation
Locations8 sites (Chicago, Illinois and 7 other locations)
Trial IDNCT06336291 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of L19TNF in combination with lomustine in patients with glioblastoma who are experiencing progression or recurrence. It is a randomized, open-label phase II study involving 90 participants assigned to one of six treatment arms, each receiving different doses of L19TNF and lomustine. The study aims to gather data on pharmacokinetics, pharmacodynamics, and dose-response relationships over a treatment cycle of up to 42 days. Patients will be stratified based on factors such as MGMT status and previous treatments to ensure balanced groups.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with histologically confirmed glioblastoma who have experienced progression or recurrence.

Not a fit: Patients with non-glioblastoma brain tumors or those with a Karnofsky Performance Status below 60% may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment combination could provide a new therapeutic option for patients with recurrent glioblastoma.

How similar studies have performed: While there have been studies exploring similar combinations, this specific approach with L19TNF and lomustine is novel and has not been extensively tested.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

1. Male or female, age ≥18.
2. Patients with histologically confirmed glioblastoma per 2021 WHO classification progression according to RANO criteria.
3. For operated patients, the histological report must document glioblastoma recurrence and a new MRI will need to be done at 3-5 weeks after surgery (directly before study treatment start). Study treatment will need to start minimum 4 weeks after surgery.
4. MGMT promotor status known.
5. Karnofsky Performance Status (KPS) ≥ 60%.
6. 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 (HBV-DNA is not required for patients with documented vaccination report). 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.
7. 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.
8. Male patients: male subjects able to father children must agree to use two acceptable methods of contraception throughout the study and until 6 months after last study drug administration (e.g. condom with spermicidal gel). Double-barrier contraception is required.
9. Personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
10. Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures.

    * Women of childbearing potential (WOCBP) are defined as females who have experienced menarche, are not postmenopausal (12 months with no menses without an alternative medical cause) and are not permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral oophorectomy, or bilateral salpingectomy).

Exclusion Criteria:

1. Inability to undergo contrast-enhanced MRI.
2. Anti-cancer treatment with radiation therapy, chemotherapy, targeted therapies, immunotherapy, hormones, tumor treating fields or other antitumor therapies within 4 weeks prior to study treatment start.
3. Subjects who participated in an investigational drug or device study within 4 weeks prior to study treatment start.
4. Grade ≥ 4 myelotoxicity with previous treatment of alkylating agents (e.g., TMZ, CCNU).
5. Previous treatment with Bevacizumab.
6. Previous treatment with L19TNF.
7. Previous treatment in the PH-L19TNFCCNU-02/20 study.
8. Known history of allergy to TNF, any excipient in the study medication or any other intravenously administered human proteins/peptides/antibodies.
9. Absolute neutrophil count (ANC) \< 1.5 x 10\^9/L; platelets \< 100 x 10\^9/L or hemoglobin (Hb) \< 9.0 g/dl.
10. 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.
11. Inadequate liver function (ALT, AST, ALP ≥ 2.5 x ULN or total bilirubin ≥ 1.5 x ULN).
12. INR \> 1.5 ULN.
13. 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.
14. Active or history of autoimmune disease that might deteriorate when receiving an immune-stimulatory agent, in the judgement of the investigator.
15. History within the last year of cerebrovascular disease and/or acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris.
16. Heart insufficiency (\> Grade II, New York Heart Association (NYHA) criteria).
17. Clinically significant cardiac arrhythmias or requiring permanent medication.
18. LVEF \<55% or any other abnormalities observed during baseline ECG and echocardiogram investigations that are considered as clinically significant by the investigator. Patients with a marked prolongation of QT/QTc interval (e.g., repeated demonstration of QTc \>470 milliseconds using Fredricia's QT correction formula) are excluded.
19. Uncontrolled hypertension.
20. Known arterial aneurism at high risk of rupture.
21. Ischemic peripheral vascular disease (Grade IIb-IV according to Leriche-Fontaine classification)
22. Anxiety ≥ CTCAE Grade 3.
23. Severe diabetic retinopathy such as severe non-proliferative retinopathy and proliferative retinopathy.
24. Major trauma including major surgery (such as abdominal/cardiac/thoracic surgery) within 3 weeks of administration of study treatment.
25. Known active or latent tuberculosis (TB).
26. Pregnancy or breast feeding.
27. Requirement of chronic administration of high dose corticosteroids or other immunosuppressant drugs. Subjects must have been either off corticosteroids, or on a stable or decreasing dose ≤ 4 mg daily dexamethasone (or equivalent) for 7 days prior to start of treatment. Limited or occasional use of corticosteroids to treat or prevent acute adverse reactions is not considered an exclusion criterion.
28. Presence of active and uncontrolled infections or other severe concurrent disease, which, in the opinion of the investigator, would place the patient at undue risk or interfere with the study.
29. Concurrent malignancies unless the patient has been disease-free without intervention for at least 2 years.
30. Growth factors or immunomodulatory agents within 7 days prior to the administration of study treatment.
31. Serious, non-healing wound, ulcer, or bone fracture.
32. Deep vein thrombosis, pulmonary embolism or other acute vascular events within 6 months.
33. Anticoagulation therapy with P2Y12 antagonists (e.g., clopidogrel, ticagrelor) and vitamin K antagonists (e.g., phenprocoumon, warfarin).
34. Requirement of concurrent use of other anti-cancer treatments or agents other than study medication.
35. Any recent live vaccination within 4 weeks prior to treatment or plan to receive live vaccination during the study.

Where this trial is running

Chicago, Illinois and 7 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions GlioblastomaL19TNFGlioblastoma at progression
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.