Study of Ad-RTS-hIL-12 + Veledimex in Combination With Cemiplimab in Subjects With Recurrent or Progressive Glioblastoma

NCT04006119 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: ATI001-204
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 7

Brief Summary

This research study involves an investigational product: Ad-RTS-hIL-12 given with veledimex for production of human IL-12. IL-12 is a protein that can improve the body's natural response to disease by enhancing the ability of the immune system to kill tumor cells and may interfere with blood flow to the tumor. Cemiplimab-rwlc (Libtayo) is an antibody (a kind of human protein) that is being tested to see if it will allow the body's immune system to work against glioblastoma tumors. Libtayo (cemiplimab-rwlc) is currently FDA approved in the United States for metastatic cutaneous cell carcinoma (CSCC), but is not approved in glioblastoma. Cemiplimab-rwlc may help your immune system detect and attack cancer cells. Ad-RTS-hIL-12 and veledimex will be given in combination with cemiplimab-rwlc to enhance the IL-12 mediated effect observed to date. The main purpose of this study is to evaluate the safety and efficacy of a single tumoral injection of Ad-RTS-hIL-12 given with oral veledimex in combination with cemiplimab-rwlc.

Conditions

Glioblastoma

Outcome Measures

Primary Outcomes (2)

• Safety of Intratumoral Ad-RTS-hIL-12 and Oral Veledimex in Combination With Cemiplimab-rwlc in Subjects With Recurrent or Progressive Glioblastoma.

  Evaluation of adverse events as assessed by CTCAE v5.0 will be based on the incidence, intensity and type of adverse event. Safety evaluations included the observed incidence of treatment-emergent adverse events (TEAEs), serious TEAEs, TEAEs of toxicity Grade \>3, TEAEs leading to treatment dose modification, discontinuation, and death. Drug-related TEAEs were also assessed.

  2.0 yrs

• Efficacy of Intratumoral Ad-RTS-hIL-12 and Oral Veledimex in Combination With Cemiplimab-rwlc in Subjects With Recurrent or Progressive Glioblastoma.

  Overall Survival (OS) OS is defined as the duration of time from the first dose of study drug (i.e., cemiplimab at Day -7) to the date of death from any cause. Censoring will be considered as below: * Subjects who discontinue study will be censored at date of discontinuation. * Subjects who are lost to follow-up will be censored at last follow-up contact date. * If the subject has not died, the subject is censored if still alive up to 2 years from the first dose of study drug received.

  2.0 yrs

Secondary Outcomes (7)

• To Determine the Survival Rates at 6, 12, and 18 Months

  From Day 0 through 18 months post first dose of study treatment

• To Determine the Progression Free Survival (PFS)

  2.0 yrs

• To Determine the Rate of Pseudoprogression (PSP) at 6, 12, 18 and 24 Months

  2 years

• To Determine the Investigator's Assessment of Response, Including Tumor Objective Response Rate (ORR) at 6, 12, 18 and 24 Months

  2 years

• To Determine the Tumor Response Rates at 6, 12, 18 and 24 Months

  2 years

Study Arms (1)

Ad-RTS-hIL-12 + veledimex in combination with cemiplimab-rwlc

EXPERIMENTAL

Intratumoral Ad-RTS-hIL-12 and oral veledimex (activator ligand, 20mg) given in combination with cemiplimab-rwlc via infusion.

Biological: Ad-RTS-hIL-12; Drug: Veledimex; Drug: Cemiplimab-Rwlc

Interventions

Ad-RTS-hIL-12 BIOLOGICAL

* intratumoral injection of Ad-RTS-hIL-12 * 2.0 x 10\^11 viral particles (vp) per injection

Ad-RTS-hIL-12 + veledimex in combination with cemiplimab-rwlc

Veledimex DRUG

20mg/day 15 oral daily doses of veledimex

Ad-RTS-hIL-12 + veledimex in combination with cemiplimab-rwlc

Cemiplimab-Rwlc DRUG

Infusion every 3 weeks (350mg)

Also known as: Libtayo, REGN2810

Ad-RTS-hIL-12 + veledimex in combination with cemiplimab-rwlc

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subject ≥18 and ≤75 years of age
• Provision of written informed consent for tumor resection (subtotal allowed), tumor biopsy, samples collection, and treatment with investigational products prior to undergoing any study-specific procedures
• Histologically confirmed glioblastoma from archival tissue
• Evidence of tumor recurrence/progression by magnetic resonance imaging (MRI) according to Response Assessment in Neuro-Oncology (RANO) criteria after standard initial therapy. Multifocal disease is allowed.
• Previous standard-of-care antitumor treatment including surgery and/or biopsy and chemoradiation. At the time of registration, subjects must have recovered from the toxic effects of previous treatments as determined by the treating physician. The washout periods from prior therapies are intended as follows: (windows other than what is listed below should be allowed only after consultation with the Medical Monitor)
• Nitrosoureas: 6 weeks
• Other cytotoxic agents: 4 weeks
• Antiangiogenic agents: 4 weeks
• Targeted agents, including small molecule tyrosine kinase inhibitors: 2 weeks
• Vaccine-based or CAR-T therapy: 3 months
• Able to undergo standard MRI scans with contrast agent before enrollment and after treatment
• Karnofsky Performance Status ≥70
• Adequate bone marrow reserves and liver and kidney function, as assessed by the following laboratory requirements:
• Hemoglobin ≥9 g/L
• Lymphocytes \>500/mm3

You may not qualify if:

• Radiotherapy treatment within 4 weeks of starting veledimex
• Prior treatment of disease with bevacizumab (NOTE: short use (\< 4 doses) of bevacizumab for controlling edema is allowed)
• Subjects receiving systemic corticosteroids for treatment of disease-related symptoms during the 4 weeks prior to Day -7
• Subjects with clinically significant increased intracranial pressure (e.g., impending herniation or requirement for immediate palliative treatment) or uncontrolled seizures
• Uncontrolled infection with human immunodeficiency virus, hepatitis B or hepatitis C infection; or diagnosis of immunodeficiency. NOTE:
• Subjects with known HIV infection who have controlled infection (undetectable viral load (HIV RNA PCR) and CD4 count above 350 either spontaneously or on a stable antiviral regimen) are permitted. For Subjects with controlled HIV infection, monitoring will be performed per local standards.
• Subjects with hepatitis B (HBsAg+) who have controlled infection (serum hepatitis B virus DNA PCR that is below the limit of detection AND receiving anti-viral therapy for hepatitis B) are permitted. Subjects with controlled infections must undergo periodic monitoring of HBV DNA. Patients must remain on anti-viral therapy for at least 6 months beyond the last dose of investigational study drug.
• Subjects who are hepatitis C virus antibody positive (HCV Ab+) who have controlled infection (undetectable HCV RNA by PCR either spontaneously or in response to a successful prior course of anti-HCV therapy) are permitted.
• Use of systemic antibacterial, antifungal, or antiviral medications for the treatment of acute clinically significant infection within 2 weeks of first veledimex dose. Concomitant therapy for chronic infections is not allowed. Subjects must be afebrile prior to Ad-RTS-hIL-12 injection; only prophylactic antibiotic use is allowed perioperatively.
• Use of enzyme-inducing antiepileptic drugs (EIAED) within 7 days prior to the first dose of study drug. Note: Levetiracetam (Keppra®) is not an EIAED and is allowed.
• Other concurrent clinically active malignant disease, requiring treatment, except for non-melanoma cancers of the skin or carcinoma in situ of the cervix or non-metastatic prostate cancer
• Nursing or pregnant females
• Prior exposure to veledimex
• Use of an investigational product within prior 30 days.
• Prior exposure to inhibitors of immuno-checkpoint pathways (e.g., anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody) or other agents specifically targeting T cells

Sponsors & Collaborators

• Alaunos Therapeutics: lead

Study Sites (7)

Cedars Sinai

Los Angeles, California, 90048, United States

Location

University of California - San Francisco

San Francisco, California, 94158, United States

Location

Baptist MD Anderson Cancer Center

Jacksonville, Florida, 32207, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

Brigham and Women's

Boston, Massachusetts, 02115, United States

Location

JFK Medical Center

Edison, New Jersey, 08820, United States

Location

NYU Langone Health

New York, New York, 10016, United States

Location

Related Publications (1)

• Chiocca EA, Gelb AB, Chen CC, Rao G, Reardon DA, Wen PY, Bi WL, Peruzzi P, Amidei C, Triggs D, Seften L, Park G, Grant J, Truman K, Buck JY, Hadar N, Demars N, Miao J, Estupinan T, Loewy J, Chadha K, Tringali J, Cooper L, Lukas RV. Combined immunotherapy with controlled interleukin-12 gene therapy and immune checkpoint blockade in recurrent glioblastoma: An open-label, multi-institutional phase I trial. Neuro Oncol. 2022 Jun 1;24(6):951-963. doi: 10.1093/neuonc/noab271.

  PMID: 34850166 DERIVED

MeSH Terms

Conditions

Glioblastoma

Interventions

veledimex; cemiplimab

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

Results Point of Contact

• Title: Jaymes Holland, Clinical Consultant
• Organization: Alaunos Therapeutics, Inc

jholland@alaunos.com

6502732627

Study Officials

• Jaymes Holland

  Alaunos Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: June 28, 2019
• First Posted: July 2, 2019
• Study Start: August 1, 2019
• Primary Completion: August 5, 2021
• Study Completion: August 5, 2021
• Last Updated: April 18, 2025
• Results First Posted: April 18, 2025

Record last verified: 2025-03

Locations

US (7)