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: Completed
• 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
• Genders Eligible for Study: Female

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
Composite measure of safety and tolerability of Ad-RTS-hIL-12 immunotherapy following a first-or second-line standard treatment in HER2-negative subjects, or together with a first- or second-line anti-HER2 antibody therapy in HER2-positive subjects	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.	2.5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression rate at 12 weeks after the start of one cycle of Ad-RTS-hIL-12 immunotherapy	2.5 years
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	2.5 years
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	2.5 years
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	2.5 years
Comparison of radiographic tumor responses by irRC with RECIST	2.5 years
Impact of treatment on serum immune biomarkers such as cytokines, chemokines, soluble receptors and antibodies to tumor antigens	2.5 years

Collaborators and Investigators

• Sponsor: Alaunos Therapeutics
• Investigators: Study Director: Francois Lebel, MD, Alaunos Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2015
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): July 1, 2016

Study Registration Dates

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

Study Record Updates

• Last Update Posted (Actual): October 8, 2021
• Last Update Submitted That Met QC Criteria: September 30, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: ATI001-203