A study to evaluate the safety and efficacy of the tumor-targeting human antibody-cytokine fusion protein L19TNF plus standard temozolomide (TMZ) chemoradiotherapy in patients with newly diagnosed glioblastoma
EU CTIS ID: 2024-516357-46-00
What this study is testing
Primary objective for Phase I: The purpose of this study is to explore the safety profile and establish a recommended dose (RD) of the antibody-cytokine fusion protein L19TNF plus standard TMZ chemoradiotherapy in patients with newly diagnosed glioblastoma. Primary objective for Phase IIb: The primary objective of the phase IIb part of the study is to investigate the efficacy profile of the antibody-cytokine fusion protein L19TNF plus standard chemoradiotherapy in patients with newly diagnosed glioblastoma with unmethylated MGMT promoter status.
- Phase I and Phase II (Integrated)- Other
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Male or female, age ≥18
- Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures.
- Patients with newly diagnosed glioblastoma per 2021 WHO classification.• Phase I part: MGMT unmethylated and methylated patients • Phase IIb part: MGMT unmethylated only
- MGMT promotor methylation status known
- Phase 2b: MRI must be available within 7248 hours after resection (if applicable)
- Karnofsky Performance Score (KPS) ≥ 70%
You likely can't join if
- Prior treatment for glioblastoma, except surgery
- 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.
- 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.
See the full eligibility criteria
Who can join
- Male or female, age ≥18
- Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures.
- Patients with newly diagnosed glioblastoma per 2021 WHO classification.• Phase I part: MGMT unmethylated and methylated patients • Phase IIb part: MGMT unmethylated only
- MGMT promotor methylation status known
- Phase 2b: MRI must be available within 7248 hours after resection (if applicable)
- Karnofsky Performance Score (KPS) ≥ 70%
- 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 (i.e., anti-HBs Ab with no history of vaccination and/or anti-HBc Ab), 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: negative pregnancy test for women of childbearing potential (WOCBP)* within 14 days of starting treatment. 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. *Women of childbearing potential 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).
- Male patients: male subjects able to father children must agree to use two acceptable methods of contraception from the screening to six months following the last treatment with radiotherapy, temozolomide and/or L19TNF (e.g. condom with spermicidal gel). Double-barrier contraception is required.
- Personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
What rules you out
- Prior treatment for glioblastoma, except surgery
- 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.
- 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.
- Abnormal LVEF or any other abnormalities observed during baseline ECG and echocardiogram investigations that are considered as clinically significant by the investigator. Subjects with current or a history of QT/QTc prolongation (e.g., repeated demonstration of QTc >470 milliseconds using Fredericia’s QT correction formula) are excluded.
- Uncontrolled hypertension.
- Known arterial aneurism at high risk of rupture.
- Ischemic peripheral vascular disease (Grade IIb-IV according to Leriche-Fontaine classification).
- Medically documented history of, or active, major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (e.g. risk of doing harm to self or others), or patients with active severe personality disorders.
- Study treatment start before 3 weeks or later than 5 weeks after glioblastoma resection (if applicable).
- Anxiety ≥ CTCAE Grade 3.
- Severe diabetic retinopathy such as severe non-proliferative retinopathy and proliferative retinopathy.
- Major trauma including major surgery (such as abdominal/cardiac/thoracic surgery) within 3 weeks of administration of study treatment.
- Known history of tuberculosis.
- Pregnancy or breast feeding.
- 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 chemoradiotherapy. Limited or occasional use of corticosteroids to treat or prevent acute adverse reactions is not considered an exclusion criterion.
- 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.
- Concurrent malignancies unless the patient has been disease-free without intervention for at least 2 years.
- Growth factors or immunomodulatory agents within 7 days prior to the administration of study treatment.
- Serious, non-healing wound, ulcer, or bone fracture.
- Inability to undergo contrast-enhanced MRI.
- Deep vein thrombosis, pulmonary embolism or other acute vascular events within 6 months.
- Anticoagulation therapy with P2Y12 antagonists (e.g., clopidogrel, ticagrelor) and vitamin K antagonists (e.g., phenprocoumon, warfarin).
- Requirement of concurrent use of other anti-cancer treatments or agents other than study medication.
- Any recent live vaccination within 4 weeks prior to treatment or plan to receive vaccination during the study.
- Commitment to an institution by virtue of an order issued either by the judicial or the administrative authorities.
- Intent to be treated with tumor-treating fields prior to progression.
- Known history of allergy to TNF or TMZ, 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, lymphocyte count < 0.8 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.
- Inadequate liver function (ALT, AST, ALP ≥ 2.5 x ULN or total bilirubin ≥ 1.5 x ULN; except for patients with Gilbert’s syndrome that may be included with serum bilirubin < 3.0 x ULN bilirubin or direct bilirubin < 1.5 x ULN).
- INR > 1.5.
The study team makes the final eligibility decision.
Where it's taking place
- Switzerland
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Switzerland. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.