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GlioblastomaPhase 2NCT04006119

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

A Phase 2 study testing Ad-RTS-hIL-12, Veledimex and Cemiplimab-Rwlc in people with Glioblastoma, run by Alaunos Therapeutics at 7 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Glioblastoma
What is being tested?
Ad-RTS-hIL-12, Veledimex and Cemiplimab-Rwlc
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
7 sitesUnited States
Study dates
1 Aug 2019to 5 Aug 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Absolute neutrophil count ≥1500/mm3
  • Platelets ≥100,000/mm3
  • Serum creatinine ≤1.5 x upper limit of normal (ULN)
  • Aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 x ULN
  • Total bilirubin <1.5 x ULN
  • International normalized ratio (INR) and activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) within normal institutional limits
  • Female of child bearing potential* and sexually active male subjects must agree to practice highly effective contraception prior to the start of the first treatment, during the study, and for at least 4 months after the last dose. Highly effective contraceptive measures include stable use of combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, transdermal) or progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation initiated 2 or more menstrual cycles prior to screening; intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal ligation; vasectomized partner; and or sexual abstinence**.
  • Postmenopausal women must be amenorrhoeic for at least 12 months in order not to be considered of childbearing potential. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation.
  • Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient.
  • Normal cardiac and pulmonary function as evidenced by a normal ECG with QTc ≤450 msec and peripheral oxygen saturation (SpO2) ≥92% on room air by pulse oximetry

Who cannot join

  • 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.
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  • 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
  • Use of medications that induce, inhibit, or are substrates of CYP450 3A4 prior to veledimex dosing without consultation with the Medical Monitor
  • Presence of any contraindication for a neurosurgical procedure
  • Use of heparin or other anti-coagulation therapy, or acetylsalicylic acid (ASA), or anti-platelet drug within Day -7 to Day 21 should not be used unless necessary to treat a life-threatening illness. Prophylactic subcutaneous heparin per institutional protocol for prevention of deep vein thrombosis (DVT) may be allowed based on discussion with the Medical Monitor. Concomitant medications should continue to be reviewed in consultation with the Medical Monitor.
  • Unstable or clinically significant 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, a history of myocarditis or congestive heart failure (as defined by New York Heart Association Functional Class III or IV), unstable angina, serious uncontrolled cardiac arrythmia, myocardial infarction within 6 months of screening, active interstitial lung disease (ILD)/pneumonitis or a history of ILD/pneumonitis requiring treatment with systemic steroids uncontrolled asthma, or colitis.

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

United States7 sites

  • Brigham and Women's

    Boston, Massachusetts, 02115

  • Northwestern Memorial Hospital

    Chicago, Illinois, 60611

  • JFK Medical Center

    Edison, New Jersey, 08820

  • Baptist MD Anderson Cancer Center

    Jacksonville, Florida, 32207

  • Cedars Sinai

    Los Angeles, California, 90048

  • NYU Langone Health

    New York, New York, 10016

  • University of California - San Francisco

    San Francisco, California, 94158

Other trials in United States

About this study

Official title: A Phase II Study of Ad-RTS-hIL-12 + Veledimex in Combination With Cemiplimab-rwlc (Libtayo®) 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.

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.

Read the detailed description

Eligible patients will receive one dose of cemiplimab-rwlc, via infusion, one week prior to standard of care craniotomy and tumor resection (subtotal or total). On the day of surgery, patients 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. Following veledimex, patients will receive cemiplimab-rwlc via infusion every three weeks.

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

Conditions
Glioblastoma
Being tested
Ad-RTS-hIL-12, Veledimex, Cemiplimab-Rwlc
Medical subject headings
Glioblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Ad-RTS-hIL-12Biological

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

  • VeledimexDrug

    20mg/day 15 oral daily doses of veledimex

  • Cemiplimab-RwlcDrug

    Also called Libtayo, REGN2810

    Infusion every 3 weeks (350mg)

Study groups in NCT04006119
Study groupRoleWhat they receive
Ad-RTS-hIL-12 + veledimex in combination with cemiplimab-rwlcExperimentalIntratumoral Ad-RTS-hIL-12 and oral veledimex (activator ligand, 20mg) given in combination with cemiplimab-rwlc via infusion.
Receives: Biological: Ad-RTS-hIL-12; Drug: Veledimex; Drug: Cemiplimab-Rwlc

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 2.0 yrs

  2. 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.

    Measured: 2.0 yrs

Secondary outcomes (7)

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

    Given the early closure of the study and survival follow-up data limited to one year post last patient in, complete assessment of efficacy could not be determined. Number of participants with death prior to each time point (6, 12, and 18 months) is reported here.

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

  2. To Determine the Progression Free Survival (PFS)

    Given the early closure of the study, formal assessment of PFS using Kaplan Meier Product-Line method was not performed. Mean time to disease progression (or participant's last scan) is reported here.

    Measured: 2.0 yrs

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

    Given the early closure of the study complete assessment of efficacy could not be determined. Reported below is the PSP at anytime while on study.

    Measured: 2 years

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

    Tumor response will be defined by radiographic and clinical criteria. Complete response (CR) or partial response (PR) will be first assessed by radiographic changes that indicate a reduction of bi-dimensional tumor size as per Recist 1.1 criteria. In addition, changes in neurologic function and steroid use will be considered to determine stable disease (SD).Given the early closure of the study complete assessment of efficacy could not be determined. The results below report response at anytime while on study.

    Measured: 2 years

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

    Given the early closure of the study and survival follow-up data limited to one year post last patient in, complete assessment of efficacy could not be determined. The IRANO results below report response at anytime while on study.

    Measured: 2 years

  6. Changes From Baseline in Cellular Responses Elicited by Ad-RTS-hIL-12 and Veledimex in Combination With Cemiplimab-rwlc

    Immune cell population markers, such as cluster of differentiation (CD) antigens CD3+CD4+ and CD3+/ CD4+/ CD25hi/ Foxp3+/ CD127lo-, were assessed.

    Measured: Screening through Day 28 (assessed at Screening and Days 0, 1, 3, 7, 14, and 28)

  7. Changes From Baseline in Humoral Immune Responses Elicited by Ad-RTS-hIL-12 and Veledimex in Combination With Cemiplimab-rwlc

    Immunological and biological markers, such as levels of interleukin-12 (IL-12) and interferon gamma (IFN-γ) were assessed in serum samples.

    Measured: Screening through Day 28 (assessed at Screening and Days 0, 1, 3, 7, 14, and 28)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Jul 2019
  2. Study start1 Aug 2019
  3. Primary completion5 Aug 2021
  4. Study completion5 Aug 2021

Why it stopped: Sponsor Decision

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04006119
Sponsor's protocol ID
ATI001-204
Status last verified
Mar 2025
First submitted
28 Jun 2019
Last updated
18 Apr 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 34850166

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ad-RTS-hIL-12, Veledimex and Cemiplimab-Rwlc in people with Glioblastoma, run by Alaunos Therapeutics at 7 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 18 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety of Intratumoral Ad-RTS-hIL-12 and Oral Veledimex in Combination With Cemiplimab-rwlc in Subjects With Recurrent or Progressive Glioblastoma. (time frame: 2.0 yrs). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04006119, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Apr 2025.

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