A Study of Ad-RTS-hIL-12 With Veledimex in Subjects With Glioblastoma or Malignant Glioma

NCT02026271 | Completed Phase 1 Results DMC

• 1 other identifier: ATI001-102
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 6

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. The main purpose of this study is to evaluate the safety and tolerability of a single tumor injection of Ad-RTS-hIL-12 given with oral veledimex.

Conditions

Glioblastoma Multiforme; Anaplastic Oligoastrocytoma

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability of Varying Doses of Intratumoral Ad-RTS-hIL-12 and Oral Veledimex Doses in Subjects With Recurrent or Progressive Glioblastoma or Grade III Malignant Glioma

  Evaluation will be based on the incidence, intensity, and type of Adverse Events (AEs). Clinically significant changes in the subjects' physical examinations, vital signs, and ECG evaluations, and clinical manifestations relevant to abnormal laboratory values will be captured as AEs.

  3 years

Secondary Outcomes (7)

• Veledimex Maximum Tolerated Dose (MTD) When Given With Varying Doses of Intratumoral Ad-RTS-hIL-12

  3 years

• Veledimex Pharmacokinetic Profile and Veledimex Concentration Ratio Between the Brain Tumor and the Blood

  15 days

• Cellular and Humoral Immune Responses Elicited by Ad-RTS-hIL-12 and Veledimex

  28 days

• Tumor Objective Response Rate (ORR)

  48 weeks

• Progression-free Survival (PFS)

  3 years

Study Arms (1)

Ad-RTS-hIL-12+veledimex

EXPERIMENTAL

varying doses of intratumoral Ad-RTS-hIL-12 (INXN-2001) and oral veledimex (activator ligand).

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

Interventions

Ad-RTS-hIL-12 BIOLOGICAL

* 2.0 x 10\^11 viral particles (vp) per injection or 1.0 x 10\^12 viral particles (vp) per injection * one intratumoral injection of Ad-RTS-hIL-12

Also known as: INXN-2001

Ad-RTS-hIL-12+veledimex

veledimex DRUG

* 4 doses (20mg/day, 40mg/day, 80mg/day, and 120mg/day) * 14 oral daily doses of veledimex * 1 Expansion cohort at a single dose level at or below MTD

Also known as: INXN-1001, Activator Ligand

Ad-RTS-hIL-12+veledimex

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 subjects ≥ 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 procedures
• Histologically confirmed supratentorial glioblastoma or other WHO grade III or IV malignant glioma from archival tissue.
• Evidence of tumor recurrence/progression by MRI (RANO criteria) post standard initial therapy.
• Previous standard of care anti-tumor treatment including surgery and/or biopsy and chemoradiation. The washout periods from prior therapies are intended as follows:
• Nitrosoureas: 6 weeks
• Other cytotoxic agents: 4 weeks
• Anti-angiogenic agents including bevacizumab: 4 weeks
• Targeted agents including small-molecule tyrosine kinase inhibitors: 2 weeks
• Experimental immunotherapies: 3 months
• Vaccine based therapy: 3 months
• Able to undergo standard MRI scans with contrast agent
• Karnofsky Performance Status ≥ 70
• Adequate bone marrow reserves and liver and kidney function, as assessed by the following laboratory requirements:
• Hemoglobin ≥ 9 g/L

You may not qualify if:

• Radiotherapy within 4 weeks or less prior to starting first veledimex dose
• Subjects with clinically significant increased intracranial pressure or uncontrolled seizures.
• Known immunosuppressive disease, autoimmune conditions, and /or chronic viral infections
• Use of systemic antibacterials, antifungals or antivirals 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 permitted perioperatively.
• Use of enzyme-inducing anti-epileptic drugs (EIAED) within 7 days prior to the first dose of study drug.
• 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 non-metastatic prostate cancer.
• Nursing or pregnant females
• Prior exposure to veledimex
• Use of medications that induce, inhibit or are substrates of CYP450 3A4 within 7 days prior to the first veledimex dosing
• Presence of any contra-indication 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.

Sponsors & Collaborators

• Alaunos Therapeutics: lead

Study Sites (6)

Cedars-Sinai

Los Angeles, California, 90048, United States

Location

University of California - San Francisco

San Francisco, California, 94143, United States

Location

Northwestern

Chicago, Illinois, 60611, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Brigham & Women's

Boston, Massachusetts, 02115, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Chiocca EA, Yu JS, Lukas RV, Solomon IH, Ligon KL, Nakashima H, Triggs DA, Reardon DA, Wen P, Stopa BM, Naik A, Rudnick J, Hu JL, Kumthekar P, Yamini B, Buck JY, Demars N, Barrett JA, Gelb AB, Zhou J, Lebel F, Cooper LJN. Regulatable interleukin-12 gene therapy in patients with recurrent high-grade glioma: Results of a phase 1 trial. Sci Transl Med. 2019 Aug 14;11(505):eaaw5680. doi: 10.1126/scitranslmed.aaw5680.

  PMID: 31413142 DERIVED

MeSH Terms

Conditions

Glioblastoma

Interventions

veledimex

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
• 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: December 16, 2013
• First Posted: January 1, 2014
• Study Start: June 1, 2015
• Primary Completion: August 1, 2019
• Study Completion: August 1, 2019
• Last Updated: April 16, 2025
• Results First Posted: April 16, 2025

Record last verified: 2025-03

Locations

US (6)