Safety Study of Adenovirus Vector Engineered to Express hIL-12 in Combination With Activator Ligand to Treat Melanoma

October 15, 2025 updated by: Alaunos Therapeutics

A Phase I/II, Open Label Study of Ad-RTS-hIL-12, an Adenovirus Vector Engineered to Express hIL-12, in Combination With an Oral Activator Ligand, in Subjects With Unresectable Stage III or IV Melanoma

This research study involves two investigational drugs, an Activator Ligand (INXN-1001) in combination with an Adenovirus Vector Engineered to Express hIL-12 (INXN-2001). IL-12 is a protein that may 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 tumor injections of INXN-2001 given in combination with different doses of INXN-1001.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Single-arm, open label, Phase I/II dose escalation study of intratumoral injections INXN-2001 and oral INXN-1001 in subjects with unresectable Stage III or IV melanoma.

Four sequential dose escalation cohorts of INXN-1001 in combination with a fixed dose of INXN-2001 are planned. Subject enrollment and dose escalation will proceed according to a standard 3+3 design.

Approximately 15 additional subjects will be enrolled as an expansion cohort at a single dose level at or below the MTD.

  • Safety and tolerability will be assessed by the incidence and severity of adverse events.
  • The antitumor activity of study treatment will be assessed according to RECIST v1.1 guidelines. Additional assessment of anti-tumor activity will be explored based on total measurable tumor burden.
  • Immunological and biological markers of response will include examinations of tumor biopsy samples, cytokine levels, peripheral blood mononuclear cells (PBMC) and antibody response to INXN-2001.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
26

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90404
        • The Angeles Clinic
    • Illinois
      • Park Ridge, Illinois, United States, 60068
        • Oncology Specialists
    • Indiana
      • Goshen, Indiana, United States, 46526
        • Indiana University Health Goshen Center for Cancer Care
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • James Graham Brown Cancer Center
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Washington University
    • New Jersey
      • Morristown, New Jersey, United States, 07960
        • Atlantic Melanoma Center
    • Pennsylvania
      • Easton, Pennsylvania, United States, 15232
        • St. Lukes
    • Texas
      • Dallas, Texas, United States, 75201
        • Mary Crowley Cancer Research Center
    • Vermont
      • Burlington, Vermont, United States, 05401
        • Fletcher Allen Health

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Males or females of all races ≥ 18 years of age, who have provided written informed consent prior to completing any study specific procedure.
  • Unresectable Stage III or Stage IV melanoma arising from any site other than ocular melanoma.
  • A minimum of 2 accessible nonvisceral lesions (shortest diameter ≥1 cm) or palpable tumor-involved lymph nodes (shortest diameter ≥1.5 cm).
  • ECOG performance status of 0 or 1 (Appendix 1).
  • Adequate bone marrow, liver, and renal function.
  • An expected survival of at least approximately 6 months.
  • Male and female subjects must agree to use a highly reliable method of birth control (expected failure rate less than 5% per year) from the screening visit through 28 days after the last dose of study drug.

Exclusion Criteria:

  • Any prior anti-cancer therapy or investigational agent within 28 days prior to the first dose of study drug. (NOTE: For the expansion cohort ONLY, if subjects received ipilimumab, a 90-day washout period since last dose of ipilimumab is required. If subjects received other immunomodulating therapies (eg, anti-PD1 antibodies), the medical monitor should be contacted and an evaluation will be made.)
  • Clinically significant infection requiring systemic antibacterial, antifungal, or antiviral therapy within 2 weeks of the first dose of study drug.
  • History of HIV infection.
  • Active autoimmune disease requiring steroids (>10 mg prednisone or comparable) or other immunosuppressive therapy (e.g., methotrexate, etc.).
  • Documented symptomatic brain metastases. Screening for brain lesions by CT or MRI is not required for all potential subjects; however, if there are any neurological signs or symptoms consistent with brain metastases, then a brain CT or MRI should be performed as clinically indicated.
  • Any medications that induce, inhibit or are substrates of CYP450 3A4 within 7 days prior to the first dose of study drug.
  • Prior history of hematopoietic stem cell transplant or organ allograft.
  • Other concurrent clinically active malignant disease, with the exception of other cancers of the skin.
  • Females who are nursing or pregnant.
  • Subjects who have a history of hypersensitivity that may relate to any component of the study drugs, e.g. to benzoic acid since INXN-1001 contains two benzene rings.
  • Unstable or clinically significant concurrent medical condition that would, in the opinion of the investigator, jeopardize the safety of a subject and/or their compliance with the protocol.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: INXN-1001 in combination with INXN-2001
Intratumoral injections of INXN-2001 (Ad-RTS-hIL-12) at a constant dose in combination with inter-cohort escalating doses of INXN-1001 (activator ligand).
Biological: INXN-2001
  • approximately 1.0 x 1012 viral particles (vp) per injection
  • one intratumoral injection of INXN-2001 per study cycle
  • maximum of 6 study cycles
Other Names:
  • Ad-RTS-hIL-12
Drug: INXN-1001
  • 4 dose cohorts (5mg/day, 20mg/day, 100mg/day, and 160mg/day)
  • 7 oral daily doses of INXN-1001 per study cycle
  • maximum of 6 study cycles
  • 1 Expansion cohort at a single dose level at or below MTD (160mg/day)
Other Names:
  • Activator Ligand

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Treatment-Emergent Adverse Events
Time Frame: From the signing of informed consent until 28 days after the last dose of study treatment, up to 28 weeks
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.
From the signing of informed consent until 28 days after the last dose of study treatment, up to 28 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Area Under the Plasma Concentration-Time Curve (AUC) of INXN-1001 (Veledimex) in Cycle 1
Time Frame: Samples were collected in Cycle 1 on Day 1 (pre-dose and 0.5, 1, 2, 4, and 6 hours post-dose), Day 2 (pre-dose), Day 7 (pre-dose and 1-2 and 4-6 hours post-dose), and Day 8 (24 hours after the Day 7 dose).
The area under the plasma concentration versus time curve from time 0 to the last measurable concentration (AUC0-t) for INXN-1001, calculated during the first treatment cycle.
Samples were collected in Cycle 1 on Day 1 (pre-dose and 0.5, 1, 2, 4, and 6 hours post-dose), Day 2 (pre-dose), Day 7 (pre-dose and 1-2 and 4-6 hours post-dose), and Day 8 (24 hours after the Day 7 dose).
Progression-Free Survival (PFS)
Time Frame: From the first dose of study treatment for up to 1 year.
Progression-Free Survival (PFS) was defined as the time in days from the first dose of study treatment to the first assessment of disease progression or death from any cause, whichever occurred first. Subjects who withdrew from the study were censored at the date of their last non-progressive disease assessment. The final analysis was performed using Kaplan-Meier methodology to determine the median PFS.
From the first dose of study treatment for up to 1 year.
Change From Baseline in Tumor IL-12 Messenger RNA (mRNA) Expression Change in IL-12 mRNA Expression Level (Arbitrary Units)
Time Frame: Baseline (Screening) and at the Post-Treatment Safety Assessment (approximately 28 days after the end of Cycle 1).

Tumor biopsy samples were analyzed for IL-12 mRNA expression using quantitative real-time polymerase chain reaction (qRT-PCR).

Expression levels were normalized to the housekeeping gene ACTB (β-actin) and quantified using the ΔΔCt method.

For each participant, the median ΔΔCt-based fold-change from baseline to post-treatment was calculated.

These individual participant-level medians were then averaged to derive the mean of medians (measure type) across all participants within each arm/group.

The reported values therefore reflect the mean of medians in arbitrary units (AU), representing relative IL-12 mRNA expression normalized to ACTB- calculated as 2^(-ΔΔCt) fold-change relative to baseline

Not all subjects in each arm contributed evaluable IL-12 mRNA expression data due to biopsy availability and RNA quality.
Baseline (Screening) and at the Post-Treatment Safety Assessment (approximately 28 days after the end of Cycle 1).
Maximum Plasma Concentration (Cmax) of INXN-1001 (Veledimex) in Cycle 1
Time Frame: Samples were collected in Cycle 1 on Day 1 (pre-dose and 0.5, 1, 2, 4, and 6 hours post-dose), Day 2 (pre-dose), Day 7 (pre-dose and 1-2 and 4-6 hours post-dose), and Day 8 (24 hours after the Day 7 dose)
The maximum observed plasma concentration (Cmax) of INXN-1001 following oral administration, as determined from plasma sample analysis during the first treatment cycle
Samples were collected in Cycle 1 on Day 1 (pre-dose and 0.5, 1, 2, 4, and 6 hours post-dose), Day 2 (pre-dose), Day 7 (pre-dose and 1-2 and 4-6 hours post-dose), and Day 8 (24 hours after the Day 7 dose)
Change From Baseline in Peripheral Blood Cytotoxic T-Lymphocytes (CTLs)
Time Frame: Baseline (Screening) and at Cycle 2, Day 7
The percentage of Cytotoxic T-Lymphocytes (CTLs) within the CD8+ T-cell population was measured from serum samples by flow cytometry to assess changes in immune cell populations.
Baseline (Screening) and at Cycle 2, Day 7
Change From Baseline in Peripheral Blood Regulatory T-cells (Tregs)
Time Frame: Baseline (Screening) and at Cycle 2, Day 7.
The percentage of Regulatory T-cells (Tregs) in peripheral blood lymphocytes was measured from serum samples by flow cytometry to assess changes in immune cell populations.
Baseline (Screening) and at Cycle 2, Day 7.
Change From Baseline in Tumor Interferon-gamma (IFN-γ) Messenger RNA (mRNA) Expression
Time Frame: Baseline (Screening) and at the Post-Treatment Safety Assessment (28 days after the end of Cycle 1).
Tumor biopsy samples were analyzed for IFN-γ mRNA expression using quantitative real-time polymerase chain reaction (qRT-PCR). This measure reports the fold change in expression from baseline. Due to very low or undetectable baseline IFN-γ expression in many tumor biopsy samples, the fold change values calculated by qRT-PCR using the delta-delta Ct method may result in large numeric values. All values reported reflect fold change from baseline and were calculated per the qRT-PCR assay standard procedures
Baseline (Screening) and at the Post-Treatment Safety Assessment (28 days after the end of Cycle 1).
Ad-RTS-hIL-12 Vector Copy Numbers in Tumor Biopsy Samples
Time Frame: Day 2 of Cycle 1, Day 2 of Cycle 2, and Day 2 of Cycle 3.
To evaluate the presence of the viral vector in the tumor, biopsy samples were assessed for vector copy numbers using a quantitative polymerase chain reaction (qPCR) assay. The results are reported as the number of vector copies per 100 nanograms (ng) of deoxyribonucleic acid (DNA).
Day 2 of Cycle 1, Day 2 of Cycle 2, and Day 2 of Cycle 3.
Best Overall Response (BOR) by RECIST 1.1 Criteria
Time Frame: From the first dose of study treatment for up to 1 year.
Best Overall Response (BOR) was a pre-specified secondary endpoint assessed according to Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. BOR is the best response recorded from the start of treatment until disease progression. Responses include Complete Response (CR), Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD).
From the first dose of study treatment for up to 1 year.
Time to Maximum Plasma Concentration (Tmax) of INXN-1001 (Veledimex) in Cycle 1
Time Frame: Samples were collected in Cycle 1 on Day 1 (pre-dose and 0.5, 1, 2, 4, and 6 hours post-dose), Day 2 (pre-dose), Day 7 (pre-dose and 1-2 and 4-6 hours post-dose), and Day 8 (24 hours after the Day 7 dose).
The time to reach the maximum observed plasma concentration (Tmax) of INXN-1001 following oral administration during the first treatment cycle.
Samples were collected in Cycle 1 on Day 1 (pre-dose and 0.5, 1, 2, 4, and 6 hours post-dose), Day 2 (pre-dose), Day 7 (pre-dose and 1-2 and 4-6 hours post-dose), and Day 8 (24 hours after the Day 7 dose).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Alaunos Therapeutics

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Jaymes Holland, Alaunos Therapeutics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2011

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2014

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 14, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 18, 2011

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 19, 2011

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 29, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 15, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ADA1001
  • ATI001-101 (Other Identifier: ZIOPHARM)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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