Safety and Efficacy of L19TNF in Patients With Isocitrate Dehydrogenase (IDH) Wildtype WHO Grade III / IV Glioma at First Relapse

NCT03779230 | Completed Phase 1

• 1 other identifier: PH-L19TNFGLIO-02/18
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 3

Brief Summary

Open label, non-randomized, mono-center Phase I/II study in subjects with IDH-wildtype WHO grade III / IV glioma at first relapse.

Conditions

Glioma of Brain

Outcome Measures

Primary Outcomes (9)

• Occurrence of Dose Limiting Toxicity (DLT)

  From the first day of treatment until the end of the DLT window (up to 21 days)

• Adverse event (AE), Serious Adverse Events (SAE) and Drug Induced Liver Injury (DILI) assessment based on CTCAE v.5.0

  From the inclusion in the study (signature of the informed consent form - ICF) until the end of follow-up (up to approximately 36 months)

• Standard laboratory (haematology, biochemistry, liver and urine analysis) parameters

  From the inclusion in the study (signature of the informed consent form - ICF) until the end of follow-up (up to approximately 36 months)

• Neurological assessment using the Neurologic assessment in Neuro-Oncology (NANO) scale

  Measurement of neurological function in neuro-oncology

  From the inclusion in the study (signature of the informed consent form - ICF) until the end of follow-up (up to approximately 36 months)

• Karnofsky Performance Status

  Assessment through a questionnaire of symptom-related restriction of activity, self-sufficiency and self-determination

  From the inclusion in the study (signature of the informed consent form - ICF) until the end of follow-up (up to approximately 36 months)

• Electrocardiogram (ECG) findings. In particular, data about QT/QTc intervals will be collected and analysed for QT/QTc prolongation potentially caused by treatment.

  From the inclusion in the study (signature of the informed consent form - ICF) until the end of follow-up (up to approximately 36 months)

• Echocardiogram (ECHO) findings. In particular, data about QT/QTc intervals will be collected and analysed for QT/QTc prolongation potentially caused by treatment.

  From the inclusion in the study (signature of the informed consent form - ICF) until the end of follow-up (up to approximately 36 months)

• Assessment of the formation of human anti-fusion protein antibodies (HAFA) against L19TNF.

  Cycle 1 day 1 - First Follow Up visit (up to approximately 9 months)

• Progression-free survival (PFS), according to iRANO (immunotherapy response assessment in neuro-oncology) criteria based on standardized MRI protocol

  At 6 months

Secondary Outcomes (3)

• Progression free survival (PFS)

  From the inclusion in the study (signature of the informed consent form - ICF) until the end of follow-up (up to approximately 12 months)

• Overall survival (OS).

  From the inclusion in the study (signature of the informed consent form - ICF) until the end of follow-up (up to approximately 36 months)

• Overall Response Rate (ORR, consisting of Complete and partial Response), based on iRANO criteria.

  At 12 weeks, 18 weeks, 24 weeks, 36 weeks, 48 weeks

Study Arms (1)

L19TNF

EXPERIMENTAL

Patients will be assigned to the following increasing dose levels of L19TNF: 10 and 13 μg/kg.

Drug: L19TNF

Interventions

L19TNF DRUG

Patients will be assigned to the following increasing dose levels of L19TNF: 10 and 13 μg/kg.

Also known as: onfekafusp alpha

L19TNF

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, age 18 or more
• Patients with histologically confirmed IDH-wildtype WHO grade III / IV glioma at first relapse
• Radiographic demonstration of disease progression
• Presence of at least one lesion of bi-dimensionally measurable disease by MRI of at least 1 cm (10 mm) in the longest diameter on baseline MRI.
• Karnofsky Performance Score (KPS) ≥ 70%
• Documented negative test for HIV-HBV-HCV. For HBV serology: the determination of HBsAg, anti-HBsAg-Ab 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. 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 six 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, progesteron-only or combined (estrogen- and progesteron-containing) hormonal contraception associated with inhibition of ovulation, intrauterine devices, intrauterine hormone-releasing systems, bilateral tubal occlusion or vasectomized partner.
• 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.
• Negative TB test (e.g. Mantoux or Quantiferon assay).
• Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
• Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures \*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)

You may not qualify if:

• Second or later glioma progression.
• Surgical resection or biopsy of glioma within 4 weeks of the start of study treatment.
• Subjects who participated in an investigational drug or device study within 4 weeks prior to study treatment start.
• Treatment with tumor-treating fields
• Radiotherapy within 6 weeks prior to study treatment start.
• Patients unable to undergo contrast-enhanced MRI.
• Patient taking herbal medications within 7 days prior to first dose of the study drug.
• Known history of allergy to TNF, excipient in 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 haemoglobin (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 ≥ 2.0 x 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.
• 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.

Sponsors & Collaborators

• Philogen S.p.A.: lead

Study Sites (3)

Inselspital Bern

Bern, 3010, Switzerland

Location

CHUV Départment d'Oncologie

Lausanne, CH-1011, Switzerland

Location

Universitatspital Zurich - Klinik fur Neurologie & Hirntumorzentrum

Zurich, CH-8091, Switzerland

Location

Study Officials

• Tobias Weiss, MD

  Universitätsspital Zürich

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open label, non-randomized, mono-center Phase I/II study in subjects with IDH-wildtype WHO grade III / IV glioma at first relapse.

Study Record Dates

• First Submitted: December 14, 2018
• First Posted: December 19, 2018
• Study Start: May 31, 2019
• Primary Completion: June 27, 2023
• Study Completion: June 27, 2023
• Last Updated: June 29, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

CH (3)