A Study of Ad-RTS-hIL-12 With Veledimex in Combination With Nivolumab in Subjects With Glioblastoma; a Substudy to ATI001-102

NCT03636477 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: ATI001-102 CPI Substudy 1.0
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 4

Brief Summary

This research study involves an investigational product: Ad-RTS-hIL-12 given with veledimex for production of human interleukin-12 (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. Nivolumab 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. Opdivo (Nivolumab) is currently FDA approved in the United States for melanoma (a type of skin cancer), non-small cell lung cancer, renal cell cancer (a type of kidney cancer), Hodgkin's lymphoma but is not approved in glioblastoma. Nivolumab may help your immune system detect and attack cancer cells. Ad-RTS-hIL-12 and veledimex will be given in combination with Nivolumab to enhance the IL-12 mediated effect observed to date. The main purpose of this substudy is to evaluate the safety and tolerability of a single tumoral injection of Ad-RTS-hIL-12 given with oral veledimex in combination with nivolumab.

Conditions

Glioblastoma

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Adverse Events (AEs)

  Evaluation of adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.03 will be based on the incidence, intensity and type of adverse event. AEs will be regarded as treatment-emergent adverse events (TEAEs) during the treatment period regardless of relationship to study drug if: • The AE occurred or worsened from baseline during or after administration of the first dose of study drug (on or after Day 0).

  2 years and 4 months

• Number of Participants With Veledimex Dose Compliance

  Evaluation will be based on expected dose compliance. Subjects were instructed to document veledimex dosing compliance in a subject diary, including the time each dose was taken, the time of the last meal prior to administration of veledimex, the number of capsules taken, whether the subject missed any veledimex doses, and reason for any missed doses. Investigational product container(s) with any remaining capsules were returned to the study staff on Day 15, and staff assessed dose compliance.

  From Day 0 through Day 14 for each participant

Secondary Outcomes (15)

• Number of Participants With a Dose-Limiting Toxicity (DLT)

  The first treatment cycle (21 days).

• Tumor Objective Response Rate (ORR)

  2 years and 4 months

• Progression Free Survival (PFS)

  2 years and 4 months

• Rate of Pseudo-progression (PSP)

  2 years and 4 months

• Overall Survival (OS)

  Up to 24 months

Study Arms (1)

Ad-RTS-hIL-12 + veledimex in combination with nivolumab

EXPERIMENTAL

Intratumoral Ad-RTS-hIL-12 and varying doses of oral veledimex (activator ligand) given in combination with nivolumab via infusion.

Biological: Ad-RTS-hIL-12; Drug: veledimex; Drug: Nivolumab

Interventions

Ad-RTS-hIL-12 BIOLOGICAL

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

Ad-RTS-hIL-12 + veledimex in combination with nivolumab

veledimex DRUG

* 2 doses (10mg/day, 20mg/day) * 15 oral daily doses of veledimex

Ad-RTS-hIL-12 + veledimex in combination with nivolumab

Nivolumab DRUG

* 2 doses (1mg/kg, 3mg/kg) * Every 2 weeks

Also known as: Opdivo

Ad-RTS-hIL-12 + veledimex in combination with nivolumab

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, stereotactic surgery, tumor biopsy, samples collection, and treatment with investigational products prior to undergoing any study specific procedures
• Histologically confirmed supratentorial glioblastoma
• Evidence of tumor recurrence/progression by magnetic resonance imaging (MRI) according to response assessment in neuro-oncology (RANO) criteria after standard initial therapy
• 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)
• Nitrosureas: 6 weeks
• Other cytotoxic agents: 4 weeks
• Antiangiogenic agents, including bevacizumab: 4weeks
• Targeted agents, including small molecule tyrosine kinase inhibitors: 2 weeks
• Vaccine-based 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:

• Previous treatment with inhibitors of immunocheckpoint pathways (eg, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody) or other agents specifically targeting T cells
• Radiotherapy treatment within 4 weeks or less prior to veledimex dosing
• Subjects with clinically significant increased intracranial pressure (eg, impending herniation or requirement for immediate palliative treatment) or uncontrolled seizures
• Known immunosuppressive disease, or autoimmune conditions, and/or chronic viral infections (eg, human immunodeficiency virus \[HIV\], hepatitis)
• 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, with the exception of non-melanoma cancers of the skin or carcinoma in situ of the cervix or nonmetastatic prostate cancer
• Nursing or pregnant females
• Prior exposure to veledimex
• Use of medications that induce, inhibit, or are substrates of cytochrome p450 (CYP450) 3A4 within 7 days prior to veledimex dosing without consultation with the Medical Monitor
• Presence of any contraindication for a neurosurgical procedure
• Unstable or clinically significant concurrent medical condition that would, in the opinion of the Investigator or Medical Monitor, jeopardize the safety of a subject and/or their compliance with the protocol. Examples include, but are not limited to: unstable angina, congestive heart failure, myocardial infarction within 2 months of screening, ongoing maintenance therapy for life-threatening ventricular arrhythmia or uncontrolled asthma.
• History of myocarditis or congestive heart failure (as defined by New York Heart Association Functional Classification III or IV), as well as unstable angina, serious uncontrolled cardiac arrhythmia, uncontrolled infection, or myocardial infarction 6 months prior to study entry.

Sponsors & Collaborators

• Alaunos Therapeutics: lead

Study Sites (4)

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

Brigham & Women's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, 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; Nivolumab

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)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Jaymes Holland
• Organization: Alaunos Therapeutics

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

Study Record Dates

• First Submitted: July 5, 2018
• First Posted: August 17, 2018
• Study Start: June 18, 2018
• Primary Completion: October 15, 2020
• Study Completion: June 30, 2021
• Last Updated: August 12, 2025
• Results First Posted: August 12, 2025

Record last verified: 2025-08

Locations

US (4)