A Study With L19TNF in Combination With Lomustine in Patients With Glioblastoma at Progression or Recurrence

NCT06336291 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: PH-L19TNFLOM-01/23
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 9

Brief Summary

The trial aims to collect safety, efficacy, exposure, dose- response, pharmacokinetic and pharmacodynamic information of the combination of L19TNF and lomustine at different dose levels in patients with Glioblastoma at progression or recurrence

Conditions

Glioblastoma

Keywords

L19TNF; Glioblastoma at progression

Outcome Measures

Primary Outcomes (5)

• Adverse Events

  Occurence of AEs according to CTCAE v.5.0

  From the screening, throughout the study, until demonstration of confirmed disease progression, treatment begins with another anti-cancer agent or surgery, or for a minimum of 12 months

• Serious Adverse Events

  Occurence of SAEs according to CTCAE v.5.0

  From the screening, throughout the study, until demonstration of confirmed disease progression, treatment begins with another anti-cancer agent or surgery, or for a minimum of 12 months

• Unacceptable Toxicity

  Occurence of Unacceptable Toxicity according to CTCAE v.5.0

  From the start of treatment up to 3 months

• DILI assessment

  Occurence of DILI according to CTCAE v.5.0

  From the screening, throughout the study, until demonstration of confirmed disease progression, treatment begins with another anti-cancer agent or surgery, or for a minimum of 12 months

• Survival

  Survival rate at 12 months

  From enrollment to death from any cause, for a minimum of 12 months

Secondary Outcomes (10)

• Overall Survival

  From enrollment to death from any cause, for a minimum of 12 months

• Progression Free Survival

  From enrollment to the date of progression or death from any cause, whichever came first, for a minimum of 12 months

• Objective Response Rate

  From enrollment to death from any cause, for a minimum of 12 months

• Disease Control Rate

  From enrollment to death from any cause, for a minimum of 12 months

• Duration of Response

  From enrollment to the date of progression or death from any cause, whichever came first, for a minimum of 12 months

Study Arms (6)

Arm A

EXPERIMENTAL

Patients will be treated with L19TNF on Days 1, 3 and 5, and on Days 22, 24 and 26 and Lomustine on Day 1 (in the evening after L19TNF infusion) of a 42-day cycle for up to a maximum of 6 cycles.

Drug: L19TNF; Drug: Lomustine

Arm B

EXPERIMENTAL

Patients will be treated with on Days 1, 3 and 5, and on Days 22, 24 and 26 and Lomustine on Day 1 (in the evening after L19TNF infusion) of a 42-day cycle for up to a maximum of 6 cycles

Drug: L19TNF; Drug: Lomustine

Arm C

EXPERIMENTAL

Patients will be treated with L19TNF on Days 1, 3 and 5, and on Days 22, 24 and 26 and Lomustine on Day 1 (in the evening after L19TNF infusion) of a 42-day cycle for up to a maximum of 6 cycles.

Drug: L19TNF; Drug: Lomustine

Arm D

EXPERIMENTAL

Patients will be treated with L19TNF on Days 1, 3 and 5, and on Days 22, 24 and 26 and Lomustine on Day 1 (in the evening after L19TNF infusion) of a 42-day cycle for up to a maximum of 6 cycles.

Drug: L19TNF; Drug: Lomustine

Arm E

EXPERIMENTAL

Patients will be treated with L19TNF on Days 1, 3 and 5, and on Days 22, 24 and 26 and Lomustine on Day 1 (in the evening after L19TNF infusion) of a 42-day cycle for up to a maximum of 6 cycles.

Drug: L19TNF; Drug: Lomustine

Arm F

EXPERIMENTAL

Patients will be treated with L19TNF on Days 1, 3 and 5, and on Days 22, 24 and 26 and Lomustine on Day 1 (in the evening after L19TNF infusion) of a 42-day cycle for up to a maximum of 6 cycles.

Drug: L19TNF; Drug: Lomustine

Interventions

L19TNF DRUG

7 μg/kg

Also known as: onfekafusp alfa

Arm A; Arm B

Lomustine DRUG

90 mg/m2

Arm A; Arm C; Arm E

Eligibility Criteria

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

You may qualify if:

• Male or female, age ≥18.
• Patients with histologically confirmed glioblastoma per 2021 WHO classification progression according to RANO criteria.
• 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.
• MGMT promotor status known.
• Karnofsky Performance Status (KPS) ≥ 60%.
• 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.
• 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.
• 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.
• 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 (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).

You may not qualify if:

• Inability to undergo contrast-enhanced MRI.
• Anti-cancer treatment with radiation therapy, chemotherapy, targeted therapies, immunotherapy, hormones, tumor treating fields or other antitumor therapies within 4 weeks prior to study treatment start.
• Subjects who participated in an investigational drug or device study within 4 weeks prior to study treatment start.
• Grade ≥ 4 myelotoxicity with previous treatment of alkylating agents (e.g., TMZ, CCNU).
• Previous treatment with Bevacizumab.
• Previous treatment with L19TNF.
• Previous treatment in the PH-L19TNFCCNU-02/20 study.
• Known history of allergy to TNF, 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; 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/1.73m2 or for patients older than 65 years without albuminuria or proteinuria, creatinine clearance \< 45 mL/min/1.73m2.
• Inadequate liver function (ALT, AST, ALP ≥ 2.5 x ULN or total bilirubin ≥ 1.5 x ULN).
• INR \> 1.5 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.
• Active or history of autoimmune disease that might deteriorate when receiving an immune-stimulatory agent, in the judgement 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.

Sponsors & Collaborators

• Philogen S.p.A.: lead

Study Sites (9)

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

Massachusetts General Hospital (MGH)

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center (BIDMC)

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute (DFCI)

Boston, Massachusetts, 02215, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

The University of Texas, MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Virginia (UVA)

Charlottesville, Virginia, 22903, United States

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

Lomustine

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2024
• First Posted: March 28, 2024
• Study Start: May 22, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: April 21, 2026

Record last verified: 2026-04

Locations

US (9)