Evaluation of Ad-RTS-hIL-12 + Veledimex in Subjects With Recurrent or Progressive Glioblastoma, a Substudy to ATI001-102

Protocol ATI001-102 Expansion Substudy: Evaluation of Ad-RTS-hIL-12 + Veledimex in Subjects With Recurrent or Progressive Glioblastoma

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 intratumoral injection of Ad-RTS-hIL-12 given with oral veledimex.

Study Overview

• Status: Completed
• Conditions: Glioblastoma
• Intervention / Treatment: Biological: Ad-RTS-hIL-12; Drug: veledimex

Detailed Description

Patients who are scheduled for craniotomy and tumor resection will receive one dose of veledimex before the resection procedure. Ad-RTS-hIL-12 will be administered by free-hand injection. Patients will continue on oral veledimex for 14 days.

The study is divided into three periods: the screening period, the treatment period and the follow-up period.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital
  • New York
    • New York, New York, United States, 10016
      • NYU - Langone Health
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female subject ≥18 and ≤75 years of age
• Provision of written informed consent for tumor resection, tumor biopsy, samples collection, and treatment with investigational products prior to undergoing any study specific procedures
• Histologically confirmed glioblastoma
• Evidence of supratentorial 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)

  1. Nitrosureas: 6 weeks
  2. Other cytotoxic agents: 4 weeks
  3. Antiangiogenic agents: 4 weeks (NOTE: short use (< 4 doses) of bevacizumab for controlling edema is allowed)
  4. Targeted agents, including small molecule tyrosine kinase inhibitors: 2 weeks
  5. 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:

  1. Hemoglobin ≥9 g/L
  2. Lymphocytes >500/mm3
  3. Absolute neutrophil count ≥1500/mm3
  4. Platelets ≥100,000/mm3
  5. Serum creatinine ≤1.5 x upper limit of normal (ULN)
  6. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 x ULN. For subjects with documented liver metastases, ALT and AST ≤5 x ULN
  7. Total bilirubin <1.5 x ULN
  8. International normalized ratio (INR) and activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) within normal institutional limits
• Male and female subjects must agree to use a highly reliable method of birth control (expected failure rate <5% per year) from the Screening Visit through 28 days after the last dose of study drug. Women of childbearing potential (perimenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential) must have a negative pregnancy test at screening

Exclusion Criteria:

• Previous treatment with bevacizumab for their disease (NOTE: short use (< 4 doses) of bevacizumab for controlling edema is allowed)
• Subjects receiving systemic corticosteroids during the previous 4 weeks
• Radiotherapy treatment within 4 weeks of starting veledimex
• 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 CYP4503A4 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 may include, but are not limited to, colitis, pneumonitis, unstable angina, congestive heart failure, myocardial infarction within 2 months of screening, and ongoing maintenance therapy for life-threatening ventricular arrhythmia or uncontrolled asthma

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ad-RTS-hIL-12 + veledimex; Intratumoral Ad-RTS-hIL-12 and oral veledimex	Biological: Ad-RTS-hIL-12; 2.0 x 10^11 viral particles (vp) per injection; intratumoral injection of Ad-RTS-hIL-12; Drug: veledimex; 20mg/day; 15 oral daily doses of veledimex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of Intratumoral Ad-RTS-hIL-12 and Oral Veledimex in Subjects With Recurrent or Progressive Glioblastoma Based on Evaluation of Adverse Events Summarized by Incidence, Intensity and Type of Adverse Event.	Evaluation of adverse events as assessed by CTCAE v4.03. Adverse events will be summarized based on the incidence, intensity and type of adverse event.	From the first dose of study treatment until 30 days after the last dose of veledimex, lasting approximately 5 months.
Tolerability of Intratumoral Ad-RTS-hIL-12 and Oral Veledimex in Subjects With Recurrent or Progressive Glioblastoma Will be Assessed Based on Expected Dose Compliance	The Day 0 (as applicable), and Day 1 doses of veledimex were administered by study personnel at the study center. Thereafter, subjects could self-administer the remaining once daily dose of veledimex. Subjects were instructed to document veledimex dosing compliance in a subject diary, including the time each dose was taken, the time the subject ate 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.	Days 1 through 14 of each 21-day treatment cycle, over a total treatment period of up to 6 cycles (approximately 4 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine the Overall Survival (OS) of Ad-RTS-hIL-12 + Veledimex	OS is defined as the duration of time from the first dose of study drug (Day 0) to the date of death from any cause in days or months. Subjects are censored based on the last date known to be alive. For example: Subjects who discontinue the study without documentation of additional follow-up will be censored at the date of discontinuation.; Subjects who are lost to follow-up will be censored at last follow-up contact date.; Subjects still alive up to 2 years from the first dose of study drug are classified as censored and as having completed all follow-up scheduling.	From the first dose of study drug for up to 2 years.
Veledimex Pharmacokinetic Profile: Maximum Plasma Concentration (Cmax)	The maximum plasma concentration (Cmax) of veledimex	15 days
Veledimex Pharmacokinetic Profile: Time to Maximum Plasma Concentration (Tmax)	Time to maximum plasma concentration (Tmax) of veledimex. Tmax was estimated based on time of maximum concentration (Cmax) from predose (Day 0 or 14) to predose the following day (Day 1 or 15).	15 days
Veledimex Pharmacokinetic Profile: Half-life (t1/2)	Half-life (t1/2) of veledimex	15 days
Veledimex Pharmacokinetic Profile: Area-under-the-concentration Versus Time Curve (AUC)	Area-under-the-concentration versus time curve (AUC) of veledimex from Day 14 predose to Day 15 predose. AUC was estimated using the elimination rate constant k, where k = ln(Cmax/Ctrough)/time difference and AUC is approximately Cmax/k.	15 days
Veledimex Pharmacokinetic Profile: Volume of Distribution (Vd)	Volume of distribution (Vd) of veledimex. Vd was calculated using AUC approximated as described in the Outcome Measure Description for Outcome Measure 6.	15 days
Veledimex Pharmacokinetic Profile: Clearance (CL)	Clearance (CL) of veledimex. CL was calculated using AUC approximated as described in the Outcome Measure Description for Outcome Measure 6.	15 days
Veledimex Concentration Ratio Between the Brain Tumor and the Blood	Veledimex concentration ratio was calculated based on the Day 0 tumor and plasma PK results.	Day 0 (at the time of tumor resection)
Tumor Objective Response Rate (ORR)	For the ORR calculation, responders are defined as those experiencing a confirmed complete response or confirmed partial response. Non-responders are those either with stable or progressive disease. Those subjects that cannot be assessed will be treated as non-responders for the purposes of deriving the percentage of responders and confidence intervals. Overall Response was assessed at multiple timepoints (day 56, week 16, week 24, and week 48) by the study investigators. Changes to the original plan for exploration of estimates of efficacy are summarized below. • The best overall response (BOR) endpoint was added to the efficacy assessment and reported here.	48 weeks
Progression Free Survival (PFS)	PFS (progression free survival) is the time in months from the first treatment (either veledimex or Ad-RTS-hIL-12) to the first assessment on which the overall response is reported as disease progression. Subjects withdrawing from the study will be censored at their last non progressive disease response assessment. If a subject does not have a non-progressive disease response assessment, the subject will be censored on the date of the first treatment as described above.	From the first dose of study drug for up to 2 years.
Rate of Pseudo-progression (PSP)	PSP Progression free survival was originally defined for determination of PSP requiring confirmation of progression based on RANO/iRANO criteria guidelines.	From the first dose of study drug for up to 2 years.
Changes From Baseline in Cellular Responses Elicited by Ad-RTS-hIL-12 and Veledimex	Evaluation in changes in immune cell population markers, such as CD3 and CD8 in tumor	Baseline and Week 6.
Peak Serum Concentration of Interleukin-12 (IL-12)	Serum concentrations of IL-12 were measured at multiple timepoints post-dose. For each participant, the peak (maximum) concentration observed from Day 3 through the 30-day follow-up visit was identified. This measure summarizes the mean of those individual peak concentrations.	Samples were collected at Baseline (Day 1), Day 3, Day 8, and Day 15 of Cycle 1, and at the 30-day follow-up visit.
Peak Serum Concentration of Interferon-gamma (IFN-γ)	Serum concentrations of IFN-γ were measured at multiple timepoints post-dose. For each participant, the peak (maximum) concentration observed from Day 3 through the 30-day follow-up visit was identified. This measure summarizes the mean of those individual peak concentrations.	Samples were collected at Baseline (Day 1), Day 3, Day 8, and Day 15 of Cycle 1, and at the 30-day follow-up visit

Collaborators and Investigators

• Sponsor: Alaunos Therapeutics
• Investigators: Study Director: Jaymes Holland, Alaunos Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): September 5, 2018
• Primary Completion (Actual): April 2, 2019
• Study Completion (Actual): January 19, 2021

Study Registration Dates

• First Submitted: August 29, 2018
• First Submitted That Met QC Criteria: September 19, 2018
• First Posted (Actual): September 20, 2018

Study Record Updates

• Last Update Posted (Estimated): August 28, 2025
• Last Update Submitted That Met QC Criteria: August 10, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; veledimex
• Other Study ID Numbers: ATI001-102 EXP Substudy 2.0

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No