Onfekafusp alfa for Glioblastoma

Inclusion criteria

• {"criterion_text":"- Male or female, age ≥18\n- Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures\n- Patients with histologically confirmed glioblastoma per 2021 WHO classification progression according to RANO criteria\n- 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\n- MGMT promotor status known\n- Karnofsky Performance Status (KPS) ≥ 60%.\n- 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\n- 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. *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).\n- 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\n- Personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study"}

Exclusion criteria

• {"criterion_text":"- Inability to undergo contrast-enhanced MRI\n- Previous treatment in the PH-L19TNFCCNU-02/20 study\n- Known history of allergy to TNF or lomustine, any excipient in the study medication or any other in-travenously administered human proteins/peptides/antibodies\n- Absolute neutrophil count (ANC) < 1.5 x 10^9/L; platelets < 100 x 10^9/L or hemoglo-bin (Hb) < 9.0 g/dl\n- Any severe concomitant condition which makes it undesirable for the patient to partici-pate in the study or which could jeopardize compliance with the protocol, in the opinion of the investigator\n- Active or history of autoimmune disease that might deteriorate when receiving an im-mune-stimulatory agent, in the judgement of the investigator\n- History within the last year of cerebrovascular disease and/or acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris\n- Heart insufficiency (> Grade II, New York Heart Association (NYHA) criteria)\n- Clinically significant cardiac arrhythmias or requiring permanent medication\n- LVEF <55% or any other abnormalities observed during baseline ECG and echocardio-gram investigations that are considered as clinically significant by the investigator. Pa-tients with a marked prolongation of QT/QTc interval (e.g., repeated demonstration of QTc >470 milliseconds using Fredricia’s QT correction formula) are excluded\n- Uncontrolled hypertension\n- 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\n- Known arterial aneurism at high risk of rupture\n- Ischemic peripheral vascular disease (Grade IIb-IV according to Leriche-Fontaine clas-sification)\n- Anxiety ≥ CTCAE Grade 3\n- Severe diabetic retinopathy such as severe non-proliferative retinopathy and prolifera-tive retinopathy\n- Major trauma including major surgery (such as abdominal/cardiac/thoracic surgery) with-in 3 weeks of administration of study treatment\n- Known active or latent tuberculosis (TB)\n- Pregnancy or breast feeding\n- Requirement of chronic administration of high dose corticosteroids or other immuno-suppressant 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\n- 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 inter-fere with the study\n- Concurrent malignancies unless the patient has been disease-free without intervention for at least 2 years\n- Inadequate liver function (ALT, AST, ALP ≥ 2.5 x ULN or total bilirubin ≥ 1.5 x ULN)\n- Growth factors or immunomodulatory agents within 7 days prior to the administration of study treatment\n- Serious, non-healing wound, ulcer, or bone fracture\n- Deep vein thrombosis, pulmonary embolism or other acute vascular events within 6 months\n- Anticoagulation therapy with P2Y12 antagonists (e.g., clopidogrel, ticagrelor) and vita-min K antagonists (e.g., phenprocoumon, warfarin)\n- Requirement of concurrent use of other anti-cancer treatments or agents other than study medication\n- Any recent live vaccination within 4 weeks prior to treatment or plan to receive live vac-cination during the study\n- INR > 1.5 ULN\n- Anti-cancer treatment with radiation therapy, chemotherapy, targeted therapies, immu-notherapy, hormones, tumor treating fields or other antitumor therapies within 4 weeks prior to study treatment start\n- Subjects who participated in an investigational drug or device study within 4 weeks pri-or to study treatment start\n- Grade ≥ 4 myelotoxicity with previous treatment of alkylating agents (e.g., TMZ, CCNU)\n- Previous treatment with Bevacizumab\n- Previous treatment with L19TNF"}

Primary endpoints

• {"endpoint_text":"- Safety endpoints: Incidence of adverse Events (AEs), Serious Adverse Events (SAEs) and Drug-Induced Liver Injury (DILI), standard labor-atory assessments, ECG, ECHO and physical examination ac-cording to CTCAE v.5.0","definition_or_measurement_approach":"Assessment according to CTCAE v.5.0; standard laboratory assessments, ECG, ECHO and physical examination as listed"}
• {"endpoint_text":"- Efficacy endpoint: Survival rate at 12 months","definition_or_measurement_approach":"Survival status measured at 12 months"}

Secondary endpoints

• {"endpoint_text":"- Progression-Free Survival (PFS)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Overall Survival (OS)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Objective Response Rate (ORR)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Disease Control Rate (DCR)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Duration of Response (DoR)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Incidence of Dose Reductions","definition_or_measurement_approach":""}
• {"endpoint_text":"- Incidence of Dose Modifications","definition_or_measurement_approach":""}
• {"endpoint_text":"- Pharmacokinetic parameters of L19TNF","definition_or_measurement_approach":""}
• {"endpoint_text":"- Assessment of the formation of Human Anti-Fusion protein Antibodies (HAFA) against L19TNF","definition_or_measurement_approach":""}

Germany

Earliest CTIS Part Ii Submission Date

31-10-2024

Latest Decision Or Authorization Date

04-12-2024

Processing Time Days

34

Number Of Sites

1

Number Of Participants

10

Italy

Earliest CTIS Part Ii Submission Date

17-10-2024

Latest Decision Or Authorization Date

09-12-2024

Processing Time Days

53

Number Of Sites

1

Number Of Participants

10

Primary sponsor

Full Name

Philogen S.p.A.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Italy