Adenoviral Vector Monotherapy or Combination With Chemotherapy in Subjects With Recurrent/Metastatic Breast Cancer.

A Phase II Randomized, Open Label Study of Ad-RTS-hIL-12 Monotherapy or Combination With Palifosfamide in Subjects With Recurrent/Metastatic Breast Cancer and Accessible Lesions

Phase II, randomized, safety and efficacy study in recurrent/metastatic breast cancer with accessible lesions.

Primary End point is rate of Progression Free Survival (PFS) at the 16 week treatment time point. Hypothesis: Adenoviral vector (Ad-RTS-hIL-12) alone and in combination with chemotherapy (palifosfamide) is safe and efficacious.

Study Overview

• Status: Terminated
• Conditions: Breast Cancer Nos Metastatic Recurrent
• Intervention / Treatment: Genetic: Ad-RTS-hIL-12 and Veledimex; Drug: Palifosfamide

Detailed Description

Multicenter, open-label, randomized study evaluating the safety and efficacy of INXN-1001 (veledimex) and INXN-2001 (Ad-RTS-hIL-12) alone and in combination with palifosfamide.

Part 1 is the safety run-in where a safety assessment will be made after 1 cycle of therapy.

Part 2, eligible subjects will be randomly assigned to active treatment Arms A or C.

Once the monotherapy (Arm A) is determined to be safe and tolerable, Part 1 combination therapy (Arm C) will begin.

Subjects should receive six cycles of study treatment, in the absence of meeting withdrawal criteria.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Baptist Cancer Institute
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Montana
    • Billings, Montana, United States, 59101
      • Billings Clinic
  • Ohio
    • Middletown, Ohio, United States, 45042
      • Signal Point Clinical Research Center
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Greenville Hospital System
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • The Jones Clinic, PC
  • Texas
    • Dallas, Texas, United States, 75201
      • Mary Crowley Medical Research Center
  • Washington
    • Spokane, Washington, United States, 99218
      • Evergreen Hematology & Oncology

Participation Criteria

Eligibility Criteria

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

Description

Inclusion criteria:

1. Males or females ≥ 18 years of age
2. Histologically or cytologically confirmed adenocarcinoma of the breast, either locally recurrent or metastatic disease with injectable lesions, for which no proven curative therapy exists.
3. Failed or progressed on at least 1 prior systemic chemotherapy regimen ± biologic/experimental therapy (if first-line therapy, failure or progression during the first 30 days).
4. Resolution of all treatment-related toxicities to Grade 1 severity or lower, except for stable sensory neuropathy ≤ Grade 2 and alopecia.
5. A minimum of 2 lesion(s) assessed by imaging using mRECIST v1.1.
6. Eastern Cooperative Oncology Group performance status 0, 1, 2
7. Male and female subjects must agree to use a highly reliable method of birth control.

8. Adequate bone marrow reserve as indicated by:

   1. Absolute neutrophil count > 1500/μL (without use of growth factors within 7 days)
   2. Absolute lymphocyte count > 700/μL (without use of growth factors within 7 days)
   3. Platelet count > 100,000/mm3 (without transfusion in prior 7 days)
   4. Hemoglobin > 9.0 g/dL (without transfusion in prior 7 days)
9. Estimated glomerular filtration rate using the Modification of Diet in Renal Disease equation: eGFR ≥ 60 mL/min/1.73 m2

10. Adequate liver function as evidenced by the following:

    1. Bilirubin ≤ 1.5 times the upper limits of normal (ULN)
    2. Alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤ 2.5×ULN, in the case of liver metastases ≤ 5×ULN

Exclusion Criteria:

1. Subjects with human epidermal growth factor receptor 2 (HER2)/neu-positive (immunohistochemistry [IHC]) 3+ or fluorescence in situ hybridization-amplified) breast tumors who are eligible for, but who have not received HER2-targeted therapy (eg, trastuzumab)
2. Concomitant anticancer therapies

3. Prior therapies discontinuation periods:

   1. Radiation within 3 weeks of enrollment
   2. Chemotherapy within 4 weeks of enrollment
   3. Nitrosoureas within 6 weeks of enrollment
   4. Biologic therapy and/or immunomodulatory therapy, checkpoint inhibitors within 6 weeks of enrollment
   5. No washout period is required for endocrine therapy
4. Radiation therapy encompassing >25% of bone marrow
5. History of bone marrow or stem cell transplantation
6. Any congenital or acquired condition leading to inability to generate an immune response

7. Immunosuppressive therapy:

   1. Systemic immunosuppressive drugs including corticosteroids (prednisone equivalent >10 mg/day)
   2. Immune suppression/requiring immunosuppressive drugs, including organ allografts
   3. Active autoimmune disease requiring the equivalent of >10 mg/day of prednisone
8. Major surgery within 4 weeks of study treatment
9. History of prior malignancy, unless the prior malignancy was diagnosed and definitively treated ≥5 years previously with no subsequent evidence of recurrence
10. Subjects with brain or subdural metastases, unless local therapy has completed and corticosteroids have been discontinued for this indication for ≥4 weeks before starting study treatment.
11. Any medications that induce, inhibit, or are substrates of cytochrome P450 (CYP450) 3A4 within 7 days prior to the first dose of study drug
12. Subjects with meningeal carcinomatosis
13. Known significant hypersensitivity to study drugs or excipients
14. History of malabsorption syndrome or other condition that would interfere with enteral absorption
15. International Normalized Ratio (INR) and activated partial thromboplastin time [PTT] <1.5 x ULN, if not therapeutically anticoagulated.
16. New York Heart Association (NYHA) Class II or greater congestive heart failure OR active ventricular arrhythmia requiring medication
17. Any other unstable or clinically significant concurrent medical condition
18. Localized infection at site of injectable lesion(s) requiring antiinfective therapy within 2 weeks of the first dose of study drug.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ad-RTS-hIL-12 and veledimex; Experimental study drug monotherapy arm (A)	Genetic: Ad-RTS-hIL-12 and Veledimex; Oral activator ligand with adenoviral vector injection of cancer lesions; Other Names: Adenoviral Vector; Oral activator ligand
Experimental: Ad-RTS-hIL-12 and Palifosfamide; Study drug combination therapy arm (C)	Genetic: Ad-RTS-hIL-12 and Veledimex; Oral activator ligand with adenoviral vector injection of cancer lesions; Other Names: Adenoviral Vector; Oral activator ligand; Drug: Palifosfamide; Small molecule chemotherapy, IV administration; Other Names: Pali

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	This measure will capture the incidence of Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and AEs leading to discontinuation. As per the protocol, safety and tolerability were assessed by monitoring adverse events, physical examinations, vital signs, electrocardiograms (ECGs), and clinical laboratory evaluations.	16 months
16-Week Progression-Free Survival (PFS) Rate	This is the primary efficacy endpoint, defined as the proportion of subjects who had not progressed or died prior to 16 weeks from the date of their first dose. Progression was determined by modified Response Evaluation Criteria in Solid Tumors	16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best Overall Response (BOR) by mRECIST v1.1	Best Overall Response (BOR) was determined for each evaluable subject up to their final tumor assessment. Per the modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1, responses were defined as: Complete Response (CR), disappearance of all non-nodal target lesions and reduction in short axis of pathological lymph nodes to <10 mm; Partial Response (PR), at least a 30% decrease in the sum of diameters of target lesions from baseline; Progressive Disease (PD), at least a 20% increase in the sum of diameters from the smallest sum recorded; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD	24 weeks
Estimate PFS by Modified RECIST v1.1	Progression-free survival (PFS) is the time in days from the first dose of study treatment to the first assessment on which the response is reported as disease progression or death due to any cause (whichever is first) + 1 day. Subjects withdrawing from the study will be censored at their last non-progressive disease response assessment. If a subject does not have a disease response assessment, the subject will be censored on the date of the first treatment as described above. Kaplan-Meier plots will not be presented; PFS will be listed only.	16 months
Area Under the Plasma Concentration-Time Curve From 0 to 24 Hours (AUC0-24) of INXN-1001	The area under the plasma concentration versus time curve from time 0 to 24 hours (AUC0-24) for INXN-1001	Cycle 1 Day 1 and Cycle 1 Day 7
Change From Baseline in MUC-1 Specific T-Cell Response by ELISPOT Assay	To assess for a cellular immune response, the number of MUC-1 specific interferon-gamma (IFN-γ) secreting T-cells was measured from peripheral blood mononuclear cells (PBMCs) using an ELISPOT assay. Results are reported as spot-forming cells (SFC) per million PBMCs	Screening and the Post-Treatment Safety Assessment visit (28 days after the last dose of study drug), with the final assessment occurring up to 7 months after the start of treatment.
Change From Baseline in Serum Interferon-gamma (IFN-γ) Levels	Serum levels of IFN-γ were measured by immunoassay to assess the pharmacodynamic effect of the treatment	Screening, 24 hours after the first injection (Day 2), and at the Post-Treatment Safety Assessment visit, with the final assessment occurring up to 7 months after the start of treatment.
Change From Baseline in Serum Interleukin-12 (IL-12) Levels	Serum levels of IL-12 were measured by immunoassay to assess the pharmacodynamic effect of the treatment	Screening, 24 hours after the first injection (Day 2), and at the Post-Treatment Safety Assessment visit, with the final assessment occurring up to 7 months after the start of treatment.
Change From Baseline in CD3+ CD4+ T-Cell Count	Absolute counts of CD3+ CD4+ helper T-cells in peripheral blood were measured by flow cytometry to evaluate changes in immune cell populations.	Screening, Cycle 1 the Post-Treatment Safety Assessment visit Day 28 ± 3, and Follow-Up Tumor Assessment visits Day 63 ± 7
Change From Baseline in CD3+ CD8+ T-Cell Count	Absolute counts of CD3+ CD8+ cytotoxic T-cells in peripheral blood were measured by flow cytometry to evaluate changes in immune cell populations	Screening, Cycle 1 the Post-Treatment Safety Assessment visit Day 28 ± 3, and Follow-Up Tumor Assessment visits Day 63 ± 7
Maximum Plasma Concentration (Cmax) of INXN-1001	The maximum observed plasma concentration (Cmax) of INXN-1001 following oral administration.	Cycle 1 Day 1 and Cycle 1 Day 7. On Day 1, samples were collected pre-dose and at 0.5, 1, 2, 4, and 6 hours post-dose. On Day 7, samples were collected pre-dose and at 1-2 and 4-6 hours post-dose
Time to Maximum Plasma Concentration (Tmax) of INXN-1001	The time to reach the maximum observed plasma concentration (Tmax) of INXN-1001 following oral administration	Cycle 1 Day 1 and Cycle 1 Day 7
Clinical Benefit Rate (CBR)	Clinical Benefit Rate (CBR) was a pre-specified secondary endpoint defined as the proportion of subjects with a best overall response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD), as assessed by modified RECIST (mRECIST) v1.1.	From the first dose of study treatment for up to 1 year.

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): April 4, 2013
• Primary Completion (Actual): August 7, 2014
• Study Completion (Actual): August 7, 2014

Study Registration Dates

• First Submitted: August 29, 2012
• First Submitted That Met QC Criteria: October 9, 2012
• First Posted (Estimated): October 10, 2012

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

• Keywords: Breast Cancer; Metastatic Breast Cancer; Recurrent Breast Cancer; Adenoviral vector; Genetically Modified Organism; Palifosfamide; INXN1001; INXN2001
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Palivizumab; veledimex; isophosphamide mustard
• Other Study ID Numbers: ATI001-201