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

NCT ID: NCT01397708

Last Updated: 2025-10-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-08-31
• Study Completion Date: 2014-09-30

Brief Summary

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.

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.

Conditions

Melanoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: EXPERIMENTAL

INXN-2001

Intervention Type: BIOLOGICAL

• approximately 1.0 x 1012 viral particles (vp) per injection
• one intratumoral injection of INXN-2001 per study cycle
• maximum of 6 study cycles

INXN-1001

Intervention Type: DRUG

• 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)

Interventions

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

Intervention Type: BIOLOGICAL

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)

Intervention Type: DRUG

Other Intervention Names

Ad-RTS-hIL-12; Activator Ligand

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Alaunos Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jaymes Holland

Role: STUDY_DIRECTOR

Alaunos Therapeutics

Locations

The Angeles Clinic

Los Angeles, California, United States

Oncology Specialists

Park Ridge, Illinois, United States

Indiana University Health Goshen Center for Cancer Care

Goshen, Indiana, United States

James Graham Brown Cancer Center

Louisville, Kentucky, United States

Washington University

St Louis, Missouri, United States

Atlantic Melanoma Center

Morristown, New Jersey, United States

St. Lukes

Easton, Pennsylvania, United States

Mary Crowley Cancer Research Center

Dallas, Texas, United States

Fletcher Allen Health

Burlington, Vermont, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

ATI001-101

Identifier Type: OTHER

Identifier Source: secondary_id

ADA1001

Identifier Type: -

Identifier Source: org_study_id