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

Status

Terminated

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02423902

Enrollment

Registered

2015-04-22

Start date

2015-07-18

Completion date

2016-07-19

Last updated

2025-08-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Metastatic Breast Cancer

Brief summary

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.

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.

Interventions

BIOLOGICALAd-RTS-hIL-12

Approximately 1.0x10\^12 viral particles (vp) per injection

DRUGVeledimex

7 oral doses of veledimex

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

FEMALE

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events Leading to Study Discontinuation	1 year	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.

Secondary

Measure	Time frame	Description
Change From Baseline in Serum Carcinoembryonic Antigen (CEA) Levels	Screening, Week 6, and Week 12.	Serum levels of the carcinoembryonic antigen (CEA) biomarker were measured by immunoassay to explore the impact of treatment.
Progression Rate at 12 Weeks After the Start of One Cycle of Ad-RTS-hIL-12 Immunotherapy	12 weeks	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)
Change From Baseline in Serum Interleukin-12 (IL-12) Levels	Screening, Week 6, and Week 12	Serum levels of Interleukin-12 (IL-12) were measured by immunoassay to explore the impact of treatment on immune biomarkers.
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	12 weeks	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.
Change From Baseline in Serum Interferon-gamma (IFN-gamma) Levels	Screening, Week 6, and Week 12	Serum levels of Interferon-gamma (IFN-gamma) were measured by immunoassay to explore the impact of treatment on immune biomarkers.
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	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
Comparison of Radiographic Tumor Responses by irRC With RECIST	12 weeks	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.
Change From Baseline in Serum CA15-3 Levels	Screening, Week 6, and Week 12	Serum levels of the cancer antigen 15-3 (CA15-3) biomarker were measured by immunoassay to explore the impact of treatment.
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	12 weeks	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.

Countries

United States

Participant flow

Participants by arm

Arm	Count
HER2+ Subjects Subjects with HER2+ breast cancer were assigned to receive an intratumoral injection of Ad-RTS-hIL-12 in combination with veledimex: * Ad-RTS-hIL-12: Approximately 1.0x10\^12 viral particles (vp) per injection * Veledimex: 7 oral doses of veledimex	1
HER2- Subjects Subjects with HER2- breast cancer were assigned to receive an intratumoral injection of Ad-RTS-hIL-12 in combination with veledimex: * Ad-RTS-hIL-12: Approximately 1.0x10\^12 viral particles (vp) per injection * Veledimex: 7 oral doses of veledimex	8
Total	9

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Disease progression	1	4

Baseline characteristics

Characteristic	HER2+ Subjects	Total	HER2- Subjects
Age, Continuous	39.0 years STANDARD_DEVIATION 0	49.6 years STANDARD_DEVIATION 10.38	50.9 years STANDARD_DEVIATION 10.24
BMI	25.5 kg/m2 STANDARD_DEVIATION 0	24.6 kg/m2 STANDARD_DEVIATION 4.71	24.5 kg/m2 STANDARD_DEVIATION 5.02
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	0 Participants	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1 Participants	8 Participants	7 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	1 Participants	1 Participants
Height	167.0 cm STANDARD_DEVIATION 0	161.8 cm STANDARD_DEVIATION 4.83	161.1 cm STANDARD_DEVIATION 4.72
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	1 Participants	1 Participants	0 Participants
Race (NIH/OMB) Black or African American	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) White	0 Participants	6 Participants	6 Participants
Sex: Female, Male Female	1 Participants	9 Participants	8 Participants
Sex: Female, Male Male	0 Participants	0 Participants	0 Participants
Weight	71.0 kg STANDARD_DEVIATION 0	64.1 kg STANDARD_DEVIATION 11.29	63.2 kg STANDARD_DEVIATION 11.75

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 1	0 / 8
other Total, other adverse events	1 / 1	8 / 8
serious Total, serious adverse events	0 / 1	4 / 8

Outcome results

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.

Time frame: 1 year

Population: The safety population will comprise all subjects who have received either the injection of Ad-RTS-hIL-12 or any doses of veledimex

Arm	Measure	Group	Value (NUMBER)
HER2+ Subjects	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events Leading to Study Discontinuation	Any TEAE	1 participants
HER2+ Subjects	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events Leading to Study Discontinuation	Treatment-related TEAE	1 participants
HER2+ Subjects	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events Leading to Study Discontinuation	Grade 3 or higher TEAE	1 participants
HER2+ Subjects	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events Leading to Study Discontinuation	Treatment-related Grade 3 or higher TEAE	1 participants
HER2+ Subjects	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events Leading to Study Discontinuation	Adverse event leading to death	0 participants
HER2+ Subjects	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events Leading to Study Discontinuation	Serious TEAE	0 participants
HER2+ Subjects	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events Leading to Study Discontinuation	TEAE leading to discontinuation	0 participants
HER2+ Subjects	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events Leading to Study Discontinuation	Cytokine Release Syndrome Assessment: Grade 2	1 participants
HER2+ Subjects	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events Leading to Study Discontinuation	Cytokine Release Syndrome Assessment: Grade 3	0 participants
HER2+ Subjects	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events Leading to Study Discontinuation	Cytokine Release Syndrome Assessment: Grade 4	0 participants
HER2- Subjects	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events Leading to Study Discontinuation	Cytokine Release Syndrome Assessment: Grade 2	5 participants
HER2- Subjects	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events Leading to Study Discontinuation	Any TEAE	8 participants
HER2- Subjects	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events Leading to Study Discontinuation	Serious TEAE	4 participants
HER2- Subjects	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events Leading to Study Discontinuation	Treatment-related TEAE	8 participants
HER2- Subjects	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events Leading to Study Discontinuation	Cytokine Release Syndrome Assessment: Grade 4	1 participants
HER2- Subjects	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events Leading to Study Discontinuation	Grade 3 or higher TEAE	7 participants
HER2- Subjects	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events Leading to Study Discontinuation	TEAE leading to discontinuation	5 participants
HER2- Subjects	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events Leading to Study Discontinuation	Treatment-related Grade 3 or higher TEAE	6 participants
HER2- Subjects	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events Leading to Study Discontinuation	Cytokine Release Syndrome Assessment: Grade 3	2 participants
HER2- Subjects	Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events Leading to Study Discontinuation	Adverse event leading to death	0 participants

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.

Time frame: Screening, Week 6, and Week 12

Population: 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.

Arm	Measure	Group	Value (MEAN)	Dispersion
HER2+ Subjects	Change From Baseline in Serum CA15-3 Levels	CA15-3 (Muc-1) at Screening	91 U/ml	Standard Deviation 0
HER2+ Subjects	Change From Baseline in Serum CA15-3 Levels	CA15-3 (Muc-1) at Week 6	138 U/ml	Standard Deviation 0
HER2- Subjects	Change From Baseline in Serum CA15-3 Levels	CA15-3 (Muc-1) at Screening	1281.5 U/ml	Standard Deviation 3500.774
HER2- Subjects	Change From Baseline in Serum CA15-3 Levels	CA15-3 (Muc-1) at Week 6	3747.5 U/ml	Standard Deviation 10430.77
HER2- Subjects	Change From Baseline in Serum CA15-3 Levels	CA15-3 (Muc-1) at Week 12	76.75 U/ml	Standard Deviation 101.6772

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.

Time frame: Screening, Week 6, and Week 12.

Population: 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.

Arm	Measure	Group	Value (MEAN)	Dispersion
HER2+ Subjects	Change From Baseline in Serum Carcinoembryonic Antigen (CEA) Levels	CEA at Screening	5.1 ng/mL	—
HER2+ Subjects	Change From Baseline in Serum Carcinoembryonic Antigen (CEA) Levels	CEA at Week 6	7.5 ng/mL	—
HER2- Subjects	Change From Baseline in Serum Carcinoembryonic Antigen (CEA) Levels	CEA at Screening	8.275 ng/mL	Standard Deviation 9.97
HER2- Subjects	Change From Baseline in Serum Carcinoembryonic Antigen (CEA) Levels	CEA at Week 6	14.838 ng/mL	Standard Deviation 21.69
HER2- Subjects	Change From Baseline in Serum Carcinoembryonic Antigen (CEA) Levels	CEA at Week 12	4.225 ng/mL	Standard Deviation 3.226

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.

Time frame: Screening, Week 6, and Week 12

Population: 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

Arm	Measure	Group	Value (MEAN)	Dispersion
HER2+ Subjects	Change From Baseline in Serum Interferon-gamma (IFN-gamma) Levels	IFN-gamma at Screening	6.34 pg/mL	—
HER2+ Subjects	Change From Baseline in Serum Interferon-gamma (IFN-gamma) Levels	IFN-gamma at Week 6	6.87 pg/mL	—
HER2- Subjects	Change From Baseline in Serum Interferon-gamma (IFN-gamma) Levels	IFN-gamma at Screening	7.34 pg/mL	Standard Deviation 10.32
HER2- Subjects	Change From Baseline in Serum Interferon-gamma (IFN-gamma) Levels	IFN-gamma at Week 6	6.51 pg/mL	Standard Deviation 6.06
HER2- Subjects	Change From Baseline in Serum Interferon-gamma (IFN-gamma) Levels	IFN-gamma at Week 12	7.02 pg/mL	Standard Deviation 6.24

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.

Time frame: Screening, Week 6, and Week 12

Population: 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.

Arm	Measure	Group	Value (MEAN)	Dispersion
HER2+ Subjects	Change From Baseline in Serum Interleukin-12 (IL-12) Levels	Il-12 at Screening	0.1505 pg/mL	—
HER2+ Subjects	Change From Baseline in Serum Interleukin-12 (IL-12) Levels	Il-12 at Week 6	0.735 pg/mL	—
HER2- Subjects	Change From Baseline in Serum Interleukin-12 (IL-12) Levels	Il-12 at Screening	0.0728 pg/mL	Standard Deviation 0.0901
HER2- Subjects	Change From Baseline in Serum Interleukin-12 (IL-12) Levels	Il-12 at Week 6	0.1476 pg/mL	Standard Deviation 0.1436
HER2- Subjects	Change From Baseline in Serum Interleukin-12 (IL-12) Levels	Il-12 at Week 12	0.0244 pg/mL	Standard Deviation 0.0221

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.

Time frame: 12 weeks