ONFEKAFUSP ALFA (onfekafusp alfa) for Glioblastoma | Glioma

Inclusion criteria

• {"criterion_text":"- Male or female, age ≥18\n- Patients with histologically confirmed newly diagnosed glioblastoma\n- Karnofsky Performance Score (KPS) ≥ 70%\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 (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\n- 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 hormonereleasing 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).\n- Male patients: male subjects able to father children must agree to use two acceptable methods of contraception throughout the study (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\n- Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures"}

Exclusion criteria

• {"criterion_text":"- Prior treatment for glioma, except surgery\n- Inability to undergo contrast-enhanced MRI\n- Intent to be treated with tumor-treating fields prior to progression\n- Known history of allergy to TNF or TMZ, any excipient in the study medication or any other intravenously administered human proteins/peptides/antibodies\n- Absolute neutrophil count (ANC) < 1.5 x 10^9/L, platelets < 100 x 10^9/L or haemoglobin (Hb) < 9.0 g/dl.\n- Chronically impaired renal function as indicated by creatinine clearance < 60 mL/min or serum creatinine > 1.5 ULN\n- Inadequate liver function (ALT, AST, ALP ≥ 2.5 x ULN or total bilirubin ≥ 2.0 x ULN).\n- INR > 1.5 ULN\n- 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\n- Active or history of autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent\n- Anxiety ≥ CTCAE Grade 3\n- Severe diabetic retinopathy such as severe non-proliferative retinopathy and proliferative retinopathy\n- Major trauma including major surgery (such as abdominal/cardiac/thoracic surgery) within 3 weeks of administration of study treatment\n- Known history of tuberculosis\n- Pregnancy or breast feeding\n- 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\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 interfere with the study\n- Concurrent malignancies unless the patient has been disease-free without intervention for at least 2 years\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- 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 vaccination during the study\n- Known arterial aneurism at high risk of rupture\n- Ischemic peripheral vascular disease (Grade IIb-IV according to Leriche-Fontaine classification)\n- Clinically significant cardiac arrhythmias or requiring permanent medication\n- 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 are excluded\n- Heart insufficiency (> Grade II, New York Heart Association (NYHA) criteria)\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- Known history of allergy to TNF or TMZ, any excipient in the study medication or any other intravenously administered human proteins/peptides/antibodies"}

Primary endpoints

• {"endpoint_text":"- For Phase I the following primary safety endpoints will be considered: − Occurrence of dose limiting toxicity (DLT) assessed by frequency and grade of adverse events (AE) according to CTCAE v.5.0.","definition_or_measurement_approach":"Occurrence of dose limiting toxicity (DLT) assessed by frequency and grade of adverse events (AE) according to CTCAE v.5.0. DLTs monitored in the defined DLT observation periods as described in protocol (see dose-finding part)."}
• {"endpoint_text":"- For Phase II the following primary endpoint will be considered: − Overall survival (OS) rate at 12 months (52 weeks).","definition_or_measurement_approach":"Overall survival (OS) rate at 12 months (52 weeks): proportion of subjects alive at 12 months from a defined baseline (time of randomization/first treatment), assessed by survival follow-up."}
• {"endpoint_text":"- For Phase IIb the following primary endpoint will be considered: − Overall survival (OS)","definition_or_measurement_approach":"Overall survival (OS): time from randomization or first study treatment to death from any cause; monitored until study completion or death."}

Secondary endpoints

• {"endpoint_text":"- For Phase I the following secondary safety endpoints will be considered: − Assessment of the formation of human anti-fusion protein antibodies (HAFA) against L19TNF. − Pharmacokinetic characterization of L19TNF. The following secondary efficacy endpoints will be considered: − Progression-free survival (PFS) based on iRANO criteria and a standardized MRI protocol. − Overall survival (OS) rate at 12 months (52 weeks). − OS. − Objective Response Rate (ORR, consisting of complete","definition_or_measurement_approach":"HAFA: assessment of anti-fusion protein antibodies against L19TNF. PK: pharmacokinetic characterization of L19TNF. PFS assessed by iRANO criteria using standardized MRI protocol. OS and OS rate at 12 months monitored by survival status. ORR per tumor response criteria (CR/PR) using iRANO and MRI."}
• {"endpoint_text":"- For Phase II the following secondary efficacy endpoints will be considered: − PFS based on iRANO criteria and a standardized MRI protocol. − OS − ORR (consisting of CR and PR) at Week 10, at Week 22, at Week 34, at Week 46 and at Week 58 − BORR The following secondary safety endpoints will be considered: − Frequency and grade of AEs, SAE and DILI according to CTCAE v.5.0 − Assessment of the formation of HAFA against L19TNF − Pharmacokinetic characterization of L19TNF","definition_or_measurement_approach":"PFS by iRANO and MRI. OS and timepoints for ORR assessments at specified weeks. BORR = best overall response rate. Safety endpoints: frequency and grade of AEs/SAEs and drug-induced liver injury (DILI) per CTCAE v5.0. HAFA and PK assessments as described."}
• {"endpoint_text":"- For Phase IIb The following secondary efficacy endpoints will be considered: − PFS based on iRANO criteria based on standardized MRI protocol. − OS rate at 12 months (52 weeks) − ORR and DCR at Week 10, at Week 22, at Week 34, at Week 46 and at Week 58 − BORR The following secondary safety endpoint will be considered: − Frequency and grade of AEs, SAEs and DILI according to CTCAE v.5.0. − Assessment of the formation of HAFA against L19TNF. − PK characterization of L19TNF.","definition_or_measurement_approach":"PFS by iRANO and MRI. OS rate at 12 months. ORR and disease control rate (DCR) assessed at specified weeks using iRANO/MRI. Safety: AEs/SAEs/DILI graded per CTCAE v5.0. HAFA and PK characterization for L19TNF."}

Germany

Earliest CTIS Part Ii Submission Date

11-02-2025

Latest Decision Or Authorization Date

18-02-2026

Processing Time Days

372

Number Of Sites

1

Number Of Participants

50

Italy

Earliest CTIS Part Ii Submission Date

28-02-2025

Latest Decision Or Authorization Date

16-02-2026

Processing Time Days

353

Number Of Sites

1

Number Of Participants

20

Primary sponsor

Full Name

Philogen S.p.A.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Italy