A Study of Ad-RTS-hIL-12 With Veledimex in Subjects With Breast Cancer

A Single-arm, Open-label Study of Ad-RTS-hIL-12 + Veledimex Following First-, Second-, or Third-Line Standard Treatment in Subjects With Locally Advanced or Metastatic Breast Cancer

This is a single-arm, phase Ib/II study to examine the safety, tolerability and preliminary efficacy of one cycle of Ad-RTS-hIL-12 immunotherapy in women with advanced breast cancer and pre-study SD or PR after completion of a minimum 12 week course of standard first- or second-line chemotherapy. The patient population will include patients with locally advanced or metastatic breast cancer of all subtypes.

Study Overview

• Status: Terminated
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Biological: Ad-RTS-hIL-12; Drug: Veledimex

Detailed Description

Subjects who have PD or a CR after the standard chemotherapy are not eligible for the study. Following entry into the trial, patients will go on a treatment holiday from chemotherapy and enter an immunotherapy phase of treatment. Continuation of HER2-targeted antibody therapy is permitted during this immunotherapy phase for women with HER2+ disease. Scans will be conducted at 6 and 12 weeks after the start of Ad-RTS-hIL-12 immunotherapy to determine tumor response. Radiographic PD at week 6 must be confirmed at least 4 weeks later, either at week 12 or earlier if clinically necessitated.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Female, age ≥ 18 years
2. Histologically-confirmed, locally advanced or metastatic adenocarcinoma of the breast
3. Achievement of SD or PR after a minimum of 12 weeks of pre-study first- or second-line standard chemotherapy
4. Presence of at least 2 measurable lesions
5. Standard treatment interrupted, except if anti-HER2 therapy
6. All treatment-related or radiation-related toxicities resolved to Grade 1 or lower
7. Submission of copies of tumor measurements and scans
8. Life expectancy > 12 weeks
9. ECOG performance status of 0 to 1
10. Adequate bone marrow function
11. Adequate liver function
12. Adequate renal function
13. Female subjects and their male partners must agree must agree to use a highly reliable method of birth control
14. Able to swallow oral medication
15. Willing to comply with study procedures

Exclusion Criteria:

1. Metastatic breast cancer patients currently on hormonal therapy as first- or second-line are not permitted
2. Prior radiation therapy encompassing > 25% of bone marrow
3. Any congenital or acquired condition leading to compromised ability to generate an immune response

4. Immunosuppressive therapy

   1. Use of systemic immunosuppressive drugs
   2. Requirement for continual immune suppression
5. Major surgery within 4 weeks of study treatment
6. An active, second potentially life-threatening cancer

7. Presence of brain or subdural metastases

   1. Any signs and/or symptoms of brain metastases must be stable for ≥ 4 weeks
   2. Radiographic stability should be determined by comparing contrast-enhanced CT or MRI scans at screening to scans obtained by the same method at least 4 weeks earlier

8. Presence or documented history of any of the following autoimmune conditions:

   1. Inflammatory bowel disease
   2. Rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematosus, autoimmune vasculitis
   3. Motor neuropathy considered of autoimmune origin
9. Presence of meningeal carcinomatosis
10. Use of any medications that induce, inhibit, or are substrates of CYP450 3A4

11. History or evidence of cardiac disease as indicated by any of the following:

    1. Congestive heart failure greater than NYHA Class II
    2. Unstable angina or new-onset angina (begun within the last 3 months), or myocardial infarction within the 6 months prior to enrollment
    3. Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
    4. Congenital long QT syndrome or taking drugs known to prolong the QT interval
12. Current use of any drugs with a known risk of causing torsades de pointes
13. Evidence or history of thromboembolic, venous, or arterial events within the past 3 months
14. Evidence or history of bleeding diathesis or coagulopathy
15. International normalized ratio (INR) and activated partial thromboplastin time (aPTT) > 1.5 x ULN, in subject who is not therapeutically anticoagulated.
16. History of malabsorption syndrome or other condition that would interfere with enteral absorption
17. Presence of active clinically serious infection
18. Diagnosis of infection with HIV or chronic infection with hepatitis B or C
19. Any other unstable or clinically significant concurrent medical condition
20. Pregnant or breast-feeding
21. Use of any investigational, non-United States Food and Drug Administration (US FDA) approved drug
22. Participation in any other clinical trial
23. Presence of any condition which makes the patient unsuitable

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 injection of Ad-RTS-hIL-12 in combination with veledimex	Biological: Ad-RTS-hIL-12; Approximately 1.0x10^12 viral particles (vp) per injection; Other Names: INXN-2001; Drug: Veledimex; 7 oral doses of veledimex; Other Names: INXN-1001 (activator ligand)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events Leading to Study Discontinuation	Composite measure of safety and tolerability based on lab parameters, vitals, physical examination data and deaths, SAEs, and AEs resulting in patient discontinuation. Toxicity stopping rules when applicable will be determined based on a clinical assessment made by the SRC. The Sponsor conducted an additional ad hoc analysis of study-drug-related-TEAEs with an onset during the dosing period of all cycles to assess the number subjects with events of cytokine release syndrome (CRS), to include TEAEs that were symptoms of CRS, including when the PI did not report the preferred term of CRS. Results of this ad hoc assessment are reported here.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Rate at 12 Weeks After the Start of One Cycle of Ad-RTS-hIL-12 Immunotherapy	The percent of subjects that failed by 12 weeks is denoted as the progression rate, and is derived based on the sum of progression events, death events, and subjects who discontinue the trial due to an AE. Tumor assessment was performed per RECIST (progression was determined as >=20% increase in the sum of the longest diameter of target lesions and or unequivocal new lesion were present)	12 weeks
Overall Response Rate (ORR), Defined as the Rate of Complete Response (CR) Plus the Rate of Partial Response (PR) at 12 Weeks Following the Start of Ad-RTS-hIL-12 Immunotherapy	Overall response at Week 12 is based on the totality of the responses for target and non-target lesions. For this calculation, responders are defined as those experiencing a CR or a PR. Non-responders are those either with stable or progressive disease. Those subjects who cannot be assessed will be treated as non-responders for the purposes of deriving the percentage of responders and confidence intervals.	12 weeks
Disease Control Rate (DCR), Defined as the Proportion of Subjects Who Have a Complete Response (CR), Partial Response (PR), or Stable Disease (SD) at 12 Weeks Following the Start of One Cycle of Ad-RTS-hIL-12 Immunotherapy	The DCR is the proportion of subjects who have a CR, PR, or stable disease at 12 weeks following the start of Ad-RTS-hIL-12 immunotherapy using RECIST v1.1. For this calculation, responders are defined as those experiencing a CR, PR, or stable disease. Non-responders are defined as those with PD. Those subjects that cannot be assessed will be treated as non-responders for the purposes of deriving the percentage of responders and confidence intervals.	12 weeks
Number of Subjects Whose Baseline Tumor Status (Stable Disease or Partial Response) Improves to Partial Response or Better at 12 Weeks Following the Start of Ad-RTS-hIL-12 Immunotherapy	Number of subjects whose baseline tumor status (stable disease or partial response) improves to partial response or better at 12 weeks following the start of Ad-RTS-hIL-12 immunotherapy	12 weeks
Comparison of Radiographic Tumor Responses by irRC With RECIST	Best Overall Response at Week 12 after 1 cycle of Ad-RTS-hIL-12 + veledimex immunotherapy is reported for response assessment per RECIST and per irRC.	12 weeks
Change From Baseline in Serum CA15-3 Levels	Serum levels of the cancer antigen 15-3 (CA15-3) biomarker were measured by immunoassay to explore the impact of treatment.	Screening, Week 6, and Week 12
Change From Baseline in Serum Interleukin-12 (IL-12) Levels	Serum levels of Interleukin-12 (IL-12) were measured by immunoassay to explore the impact of treatment on immune biomarkers.	Screening, Week 6, and Week 12
Change From Baseline in Serum Interferon-gamma (IFN-gamma) Levels	Serum levels of Interferon-gamma (IFN-gamma) were measured by immunoassay to explore the impact of treatment on immune biomarkers.	Screening, Week 6, and Week 12
Change From Baseline in Serum Carcinoembryonic Antigen (CEA) Levels	Serum levels of the carcinoembryonic antigen (CEA) biomarker were measured by immunoassay to explore the impact of treatment.	Screening, Week 6, and Week 12.

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): July 18, 2015
• Primary Completion (Actual): July 19, 2016
• Study Completion (Actual): July 19, 2016

Study Registration Dates

• First Submitted: April 6, 2015
• First Submitted That Met QC Criteria: April 21, 2015
• First Posted (Estimated): April 22, 2015

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 by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; veledimex
• Other Study ID Numbers: ATI001-203