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Safety and Efficacy of L19TNF Plus Temozolomide Chemoradiotherapy in Patients With Newly Diagnosed Glioblastoma

ConditionGlioblastoma
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorPhilogen S.p.A.

About this trial

The purpose of this study is to explore the safety profile and establish a recommended dose (RD) for phase II of the antibody-cytokine fusion protein L19TNF plus standard TMZ chemoradiotherapy in patients with newly diagnosed glioblastoma.

The study will be conducted in three consecutive parts: a dose finding part to determine the RD of L19TNF in combination with chemoradiotherapy, followed by a signal seeking part that investigates first signs of activity and then an activity evaluation part that studies the efficacy of L19TNF in combination with chemoradiotherapy against chemoradiotherapy alone.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Male or female, age ≥18.

Patients with histologically confirmed newly diagnosed glioblastoma.

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.

Disqualifiers

Prior treatment for glioma, except surgery.

Inability to undergo contrast-enhanced MRI.

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.

Trial design

Design model

Sequential

Treatments tested in this trial

  • Onfekafusp alfa

    Drug

    This is an open label phase 1/2/2b study in subjects with newly diagnosed glioblastoma. The study will be conducted in three consecutive parts: First the dose finding part to determine the RD of L19TNF in combination with chemoradiotherapy, followed by a signal seeking part that investigates first signs of activity and then an activity evaluation part that studies the efficacy of L19TNF in combination with chemoradiotherapy against chemoradiotherapy alone.

  • Temozolomide

    Drug

    Patients will receive radiotherapy and TMZ. Treatment start with chemoradiotherapy is foreseen after surgical resection or biopsy of glioblastoma

Treatment groups

226 Participants
are divided into 4 treatment groups
Group A: Phase 1 part: Dose FindingExperimental treatment 1 intervention
Group B: Phase 2 part: Signal SeekingExperimental treatment 1 intervention
Group C: Phase 2b part: Activity Evaluation_control armActive comparator 1 intervention
Group D: Phase IIb part: Activity Evaluation_treatment armExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

For Phase 1: DLT

Occurrence of dose limiting toxicity (DLT) assessed by frequency and grade of adverse events (AE) according to CTCAE v.5.0.

Time frame
For Cohort 1 and Cohort 2 from Day 1 to Day 28 of the maintenance cycle; for Cohort 3, 4 and 5 from Day 1 to Day 42 of the chemoradiotherapy.
2

For Phase 2: Overall Survival

Overall survival (OS) rate

Time frame
From beginning of treatment to 52 weeks

Secondary outcomes

1

PFS

Progression Free Survival (PFS) will be assessed for all enrolled subjects.

Time frame
From the date of enrollment to the date of progression or death for any cause, whichever came first, assessed up to 58 weeks
2

ORR in CR

Objective Response Rate (ORR): ORR is defined as the rate of patients with complete response (CR) (defined according to iRANO criteria)

Time frame
At week 10, at week 22, at week 34, at week 46 and at week 58
3

ORR in PR

Objective Response Rate (ORR): ORR is defined as the rate of patients with partial response (PR) (defined according to iRANO criteria)

Time frame
At week 10, at week 22, at week 34, at week 46 and at week 58
4

DCR in CR

Disease Control Rate (DCR) is defined as the rate of patients with complete response (CR) (defined according to iRANO criteria)

Time frame
At week 10, at week 22, at week 34, at week 46 and at week 58

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Philogen S.p.A.

Lead sponsor

Source ClinicalTrials.gov
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