Not provided
Not provided
Not provided
Not provided
Not provided
The study was terminated after 9 subjects had enrolled under Protocol Amend 1 because of slower than expected accrual. Protocol Amendment 2 (16 May 2016) was submitted to the FDA and, based on the decision of the PI, was not submitted to the IRB.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ad-RTS-hIL-12 + Veledimex | Experimental | Intratumoral injection of Ad-RTS-hIL-12 in combination with veledimex |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ad-RTS-hIL-12 | Biological | Approximately 1.0x10^12 viral particles (vp) per injection |
|
| 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 |
| 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) |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Metastatic breast cancer patients currently on hormonal therapy as first- or second-line are not permitted
Prior radiation therapy encompassing > 25% of bone marrow
Any congenital or acquired condition leading to compromised ability to generate an immune response
Immunosuppressive therapy
Major surgery within 4 weeks of study treatment
An active, second potentially life-threatening cancer
Presence of brain or subdural metastases
Presence or documented history of any of the following autoimmune conditions:
Presence of meningeal carcinomatosis
Use of any medications that induce, inhibit, or are substrates of CYP450 3A4
History or evidence of cardiac disease as indicated by any of the following:
Current use of any drugs with a known risk of causing torsades de pointes
Evidence or history of thromboembolic, venous, or arterial events within the past 3 months
Evidence or history of bleeding diathesis or coagulopathy
International normalized ratio (INR) and activated partial thromboplastin time (aPTT) > 1.5 x ULN, in subject who is not therapeutically anticoagulated.
History of malabsorption syndrome or other condition that would interfere with enteral absorption
Presence of active clinically serious infection
Diagnosis of infection with HIV or chronic infection with hepatitis B or C
Any other unstable or clinically significant concurrent medical condition
Pregnant or breast-feeding
Use of any investigational, non-United States Food and Drug Administration (US FDA) approved drug
Participation in any other clinical trial
Presence of any condition which makes the patient unsuitable
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Jaymes Holland | Alaunos Therapeutics | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Memorial Sloan Kettering Cancer Center | New York | New York | 10065 | United States |
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | HER2+ Subjects | Subjects with HER2+ breast cancer were assigned to receive an intratumoral injection of Ad-RTS-hIL-12 in combination with veledimex:
|
| FG001 | HER2- Subjects | Subjects with HER2- breast cancer were assigned to receive an intratumoral injection of Ad-RTS-hIL-12 in combination with veledimex:
|
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
The safety population will comprise all subjects who have received either the injection of Ad-RTS-hIL-12 or any doses of veledimex
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | HER2+ Subjects | Subjects with HER2+ breast cancer were assigned to receive an intratumoral injection of Ad-RTS-hIL-12 in combination with veledimex:
|
| BG001 | HER2- Subjects |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | The safety population will comprise all subjects who have received either the injection of Ad-RTS-hIL-12 or any doses of veledimex | Posted | Number | participants | 1 year |
|
1 year
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | HER2+ Subjects | Subjects with HER2+ breast cancer were assigned to receive an intratumoral injection of Ad-RTS-hIL-12 in combination with veledimex:
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Febrile Neutropenia | Blood and lymphatic system disorders | MedDRA (18.1) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | MedDRA (18.1) | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jaymes Holland | Alaunos Therapeutics | 6502732627 | jholland@alaunos.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 16, 2016 | Mar 24, 2025 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 7, 2017 | Mar 25, 2025 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000626304 | veledimex |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Veledimex | Drug | 7 oral doses of veledimex |
|
|
| 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. |
Subjects with HER2- breast cancer were assigned to receive an intratumoral injection of Ad-RTS-hIL-12 in combination with veledimex:
|
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Height | Mean | Standard Deviation | cm |
|
| Weight | Mean | Standard Deviation | kg |
|
| BMI | Mean | Standard Deviation | kg/m2 |
|
Subjects with HER2+ breast cancer were assigned to receive an intratumoral injection of Ad-RTS-hIL-12 in combination with veledimex:
|
| OG001 | HER2- Subjects | Subjects with HER2- breast cancer were assigned to receive an intratumoral injection of Ad-RTS-hIL-12 in combination with veledimex:
|
|
|
| Secondary | 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) | The veledimex-treated population will comprise subjects who have received the injection of Ad-RTS-hIL-12 and at least one dose of veledimex | Posted | Number | 95% Confidence Interval | % of subjects who progressed at 12 weeks | 12 weeks |
|
|
|
| Secondary | 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. | The veledimex-treated population will comprise subjects who have received the injection of Ad-RTS-hIL-12 and at least one dose of veledimex | Posted | Number | 95% Confidence Interval | Percentage of subjects with CR or PR | 12 weeks |
|
|
|
| Secondary | 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. | The veledimex-treated population will comprise subjects who have received the injection of Ad-RTS-hIL-12 and at least one dose of veledimex | Posted | Number | 95% Confidence Interval | Percentage of subjects with CR, PR, or S | 12 weeks |
|
|
|
| Secondary | 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 | The veledimex-treated population will comprise subjects who have received the injection of Ad-RTS-hIL-12 and at least one dose of veledimex | Posted | Number | participants | 12 weeks |
|
|
|
| Secondary | 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. | The veledimex-treated population will comprise subjects who have received the injection of Ad-RTS-hIL-12 and at least one dose of veledimex | Posted | Number | participants | 12 weeks |
|
|
|
| Secondary | 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. | The analysis was performed on the Veledimex-treated population. The number of subjects analyzed at each time point may be lower than the total due to missed sample collections. | Posted | Mean | Standard Deviation | U/ml | Screening, Week 6, and Week 12 |
|
|
|
| Secondary | 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. | The analysis was performed on the Veledimex-treated population. The number of subjects analyzed at each time point may be lower than the total due to missed sample collections. | Posted | Mean | Standard Deviation | pg/mL | Screening, Week 6, and Week 12 |
|
|
|
| Secondary | 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. | The analysis was performed on the Veledimex-treated population. The number of subjects analyzed at each time point may be lower than the total due to missed sample collections | Posted | Mean | Standard Deviation | pg/mL | Screening, Week 6, and Week 12 |
|
|
|
| Secondary | 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. | The analysis was performed on the Veledimex-treated population. The number of subjects analyzed at each time point may be lower than the total due to missed sample collections. | Posted | Mean | Standard Deviation | ng/mL | Screening, Week 6, and Week 12. |
|
|
|
| 0 |
| 1 |
| 0 |
| 1 |
| 1 |
| 1 |
| EG001 | HER2- Subjects | Subjects with HER2- breast cancer were assigned to receive an intratumoral injection of Ad-RTS-hIL-12 in combination with veledimex:
| 0 | 8 | 4 | 8 | 8 | 8 |
| Fatigue | General disorders | MedDRA (18.1) | Systematic Assessment |
|
| Malaise | General disorders | MedDRA (18.1) | Systematic Assessment |
|
| Lung Infection | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
|
| Post Procedural Haemorrhage | Injury, poisoning and procedural complications | MedDRA (18.1) | Systematic Assessment |
|
| Alanine Aminotransferase Increased | Investigations | MedDRA (18.1) | Systematic Assessment |
|
| Aspartate Aminotransferase Increased | Investigations | MedDRA (18.1) | Systematic Assessment |
|
| Oropharyngeal Pain | Respiratory, thoracic and mediastinal disorders | MedDRA (18.1) | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA (18.1) | Systematic Assessment |
|
| Palpitations | Cardiac disorders | MedDRA (18.1) | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA (18.1) | Systematic Assessment |
|
| Dry Eye | Eye disorders | MedDRA (18.1) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
|
| Gastrooesophageal Reflux Disease | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
|
| Gingival Pain | Gastrointestinal disorders | MedDRA (18.1) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (18.1) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (18.1) | Systematic Assessment |
|
| Chills | General disorders | MedDRA (18.1) | Systematic Assessment |
|
| Malaise | General disorders | MedDRA (18.1) | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA (18.1) | Systematic Assessment |
|
| Localised Oedema | General disorders | MedDRA (18.1) | Systematic Assessment |
|
| Urinary Tract Infection | Infections and infestations | MedDRA (18.1) | Systematic Assessment |
|
| Aspartate Aminotransferase Increased | Investigations | MedDRA (18.1) | Systematic Assessment |
|
| Alanine Aminotransferase | Investigations | MedDRA (18.1) | Systematic Assessment |
|
| Lymphocyte Count Decreased | Investigations | MedDRA (18.1) | Systematic Assessment |
|
| Blood Alkaline Phosphatase Increased | Investigations | MedDRA (18.1) | Systematic Assessment |
|
| Neutrophil Count Decreased | Investigations | MedDRA (18.1) | Systematic Assessment |
|
| Blood Bilirubin Increased | Investigations | MedDRA (18.1) | Systematic Assessment |
|
| White Blood Cell Count Decreased | Investigations | MedDRA (18.1) | Systematic Assessment |
|
| Decreased Appetite | Metabolism and nutrition disorders | MedDRA (18.1) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (18.1) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (18.1) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (18.1) | Systematic Assessment |
|
| Peripheral Sensory Neuropathy | Nervous system disorders | MedDRA (18.1) | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA (18.1) | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA (18.1) | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA (18.1) | Systematic Assessment |
|
| Breast Pain | Reproductive system and breast disorders | MedDRA (18.1) | Systematic Assessment |
|
| Oropharyngeal Pain | Respiratory, thoracic and mediastinal disorders | MedDRA (18.1) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (18.1) | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA (18.1) | Systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA (18.1) | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA (18.1) | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (18.1) | Systematic Assessment |
|
Not provided
| D017437 |
| Skin and Connective Tissue Diseases |
| Stable disease per RECIST |
|
| Stable disease per irRC |
|
| Progressive disease per RECIST |
|
| irRProgressive disease per irRC |
|
| CA15-3 (Muc-1) at Week 6 |
|
|
| CA15-3 (Muc-1) at Week 12 |
|
|
| Il-12 at Week 6 |
|
|
| Il-12 at Week 12 |
|
|
| IFN-gamma at Week 6 |
|
|
| IFN-gamma at Week 12 |
|
|
| CEA at Week 6 |
|
|
| CEA at Week 12 |
|
|