Diffuse Intrinsic Pontine Glioma, Pediatric Brain Tumor
Conditions
Keywords
DIPG, Glioblastoma, Anaplastic Astrocytoma, High Grade Glioma (HGG) Not Otherwise Specified (NOS), Supratentorial Tumor NOS
Brief summary
This research study involves an investigational product: Ad-RTS-hIL-12 given with veledimex for production of human IL-12. IL-12 is a protein that can improve the body's natural response to disease by enhancing the ability of the immune system to kill tumor cells and may interfere with blood flow to the tumor. The main purpose of this study is to evaluate the safety and tolerability of a single tumor injection of Ad-RTS-hIL-12 given with oral veledimex in the pediatric population.
Detailed description
Eligible patients will be stratified to one of two arms, according to clinical indication for tumor resection. Pediatric patients who are scheduled for craniotomy and tumor resection will receive one dose of veledimex before the resection procedure. Ad-RTS-hIL-12 will be administered by free-hand injection. Patients will continue on oral veledimex for 14 days. This arm has been completed and is currently closed to enrollment. Pediatric patients with diffuse intrinsic pontine glioma (DIPG) will receive Ad-RTS-hIL-12 by stereotactic injection and then will continue on oral veledimex for 14 days. The study is divided into three periods: the screening period, the treatment period and the follow-up period.
Interventions
BIOLOGICALAd-RTS-hIL-12
2.0 x 10\^11 viral particles (vp) per injection, one intratumoral injection of Ad-RTS-hIL-12
DRUGOral Veledimex - Arm 1 (Pediatric Brain Tumor)
1 dose level (10mg/day) 15 oral daily doses of veledimex
DRUGOral Veledimex - Arm 2 (DIPG)
2 dose levels (10mg/day, 20mg/day) 14 oral daily doses of veledimex
Sponsors
Alaunos Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
0 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female subjects ≤ 21 years-of-age with the demonstrated ability to swallow capsules whole and who are willing to provide access to previously obtained biopsy results 2. Provision of written informed consent and assent, when applicable, for tumor resection, stereotactic surgery, tumor biopsy, sample collection, and/or treatment with study drug prior to undergoing any study-specific procedures 3. Arm 1: Evidence of recurrent or progressive supratentorial tumor, which has shown a \> 25% increase in bi dimensional measurements by MRI or is refractory with significant neuro deterioration that is not otherwise explained with no known curative therapy, not in direct continuity with the ventricular system (e.g., there is physical separation between the tumor and ventricle, the tumor does not open directly into the ventricular system). Arm 2: Clinical presentation of DIPG and compatible MRI with approximately 2/3 of the pons included and without evidence of dissemination. Subjects should be ≥ 2 weeks and ≤ 10 weeks post standard focal radiotherapy (ie, dose of 5400 to 5960 cGy and maximum dexamethasone of 1 mg/m2/day) 4. At the time of registration, subjects must have recovered from the toxic effects of previous treatments, as determined by the treating physician. 1. Targeted agents, including small-molecular tyrosine kinase inhibitors: 2 weeks 2. Other cytotoxic agents: 3 weeks 3. Nitrosoureas: 6 weeks 4. Monoclonal antibody immunotherapies (eg, PD-1, CTLA-4): 6 weeks 5. Vaccine-based and/or viral therapy: 3 months 5. On a stable or decreasing dose of dexamethasone for the previous 7 days 6. Able to undergo standard MRI scans with contrast agent before enrollment and after treatment 7. Have age-appropriate functional performance: 1. Lansky score ≥ 40 or 2. Karnofsky score \> 50 or 3. Eastern Cooperative Oncology Group (ECOG) score ≤ 2 8. Have adequate bone marrow reserves and liver and kidney function, as assessed by the following laboratory requirements: 1. Hemoglobin ≥ 8 g/L 2. Absolute lymphocyte count ≥ 500/mm3 3. Absolute neutrophil count ≥ 1000/mm3 4. Platelets ≥ 100,000/mm3 (untransfused \[\> 5 days\] without growth factors) 5. Serum creatinine ≤ 1.5 x upper limit of normal (ULN) for age 6. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN for age 7. Total bilirubin \< 1.5 x ULN for age 8. International normalized ratio (INR) and activated thromboplastin time within normal institutional limits 9. Male and female subjects of childbearing potential must agree to use a highly reliable method of birth control (expected failure rate \< 1% per year) from the Screening visit through 28 days after the last dose of study drug. Women of childbearing potential must have a negative pregnancy test at screening.
Exclusion criteria
1. Radiotherapy treatment prior to the first veledimex dose: 1. Focal radiation ≤ 4 weeks 2. Whole-brain radiation ≤ 6 weeks 3. Cranio-spinal radiation ≤ 12 weeks NOTE: Subjects in Arm 2 (ie, with DIPG) must be ≥ 2 weeks and ≤ 10 weeks after standard focal radiotherapy (dose of 5400 to 5960 cGy and maximum dexamethasone of 1 mg/m2/day) 2. Subjects with clinically significant increased intracranial pressure (eg, impending herniation or requirement for immediate palliative treatment) or uncontrolled seizures 3. Subjects whose body surface area (BSA) would expose them to \< 75% or \> 125% of the target dose 4. Known immunosuppressive disease, autoimmune condition, and/or chronic viral infection (eg, human immunodeficiency virus \[HIV\], hepatitis) 5. Use of systemic antibacterial, antifungal, or antiviral medications for the treatment of acute clinically significant infection within 2 weeks of first veledimex dose. Concomitant therapy for chronic infections is not allowed. Subjects must be afebrile prior to Ad-RTS-hIL-12 injection; only prophylactic antibiotic use is allowed perioperatively 6. Use of enzyme-inducing antiepileptic drugs (EIAEDs) within 7 days prior to the first dose of study drug 7. Other concurrent clinically active malignant disease, requiring treatment 8. Nursing or pregnant females 9. Prior exposure to veledimex 10. Use of medications that induce, inhibit, or are substrates of cytochrome p450 (CYP450) 3A4 within 7 days prior to veledimex 11. Use of heparin or acetylsalicylic acid (ASA). The use of systemic heparinization, or any ASA containing medications, is prohibited during active dosing with veledimex. Prophylactic heparin SC, per institutional protocol, or heparin when used for maintaining patency of an access port of a PICC line is permitted. 12. Presence of any contraindication for a neurosurgical procedure 13. Unstable or clinically significant concurrent medical condition that would jeopardize the safety of a subject and/or their compliance with the protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Safety and Tolerability of Intratumoral Ad-RTS-hIL-12 and Veledimex as Measured by Dose Limiting Toxicities and Compliance. | From Day 0 through Day 56 | Dose Limiting Toxicities are defined as events that occur during the first 28 days (Day 0 - Day 28) that meets one of the following criteria: * Any local reaction that requires operative intervention and is felt to be attributable to study drug * Any local reaction that has life-threatening consequences requiring urgent intervention or results in death and is felt to be attributable to study drug * Any Grade 3 or higher non-hematologic adverse event that is at least possibly related to study drug and lasts ≥ 3 days * Nausea and vomiting will not be considered a DLT unless at least Grade 3 and refractory to antiemetics * Grade 3 or higher thrombocytopenia (\< 50,000/mm3) at least possibly related to study drug * Any Grade 4 hematologic toxicity (except thrombocytopenia) that is at least possibly related to study drug and lasts ≥ 5 days * Transient neurological changes are expected in Arm 2 and will not be considered a DLT unless they last \> 10 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | 2 Years | OS is defined as the duration of time from the first dose of the study drug to the date of death. Subjects were followed for up to 2 years. |
| Measure Immune Response of Ad-RTS-hIL-12 and Veledimex by a Quantitative Multiplex Immunoassay for Determination of IL-12 and IFNg Levels | Day 0, Day 3, Day 7, Day 14, and Day 28 | Samples for serum cytokine analysis were collected on Days 0, 3, 7, 14, and 28. For the results, participants who had samples analyzed were included in the number analyzed counts; however, values that were below the limit of quantitation (BLQ) were excluded from the calculation of mean and standard deviation. |
| To Measure the Veledimex in Blood and Brain Tumor by Using the LC-MS Method | From Day 0 through Day 15 of veledimex dosing | Veledimex brain concentration. Veledimex plasma concentration was below the limit of quantitation for most patients. Given the limited number of subjects enrolled and early closure of the study, complete assessment of veledimex in blood and brain tumor could not be determined. |
| Best Overall Response by iRANO Criteria | 2 Years | Best Overall Response was assessed using the immunotherapy Response Assessment for Neuro-Oncology (iRANO) criteria. |
| Duration of Response (DOR) | From the time of first response (CR or PR) until progression or death | Duration of Response (DOR) was defined as the time from the first documentation of a Complete Response (CR) or Partial Response (PR) to the first documentation of Progressive Disease (PD) or death due to any cause, whichever occurred first. |
| Subjects With Ad-RTS-hIL-12 and Veledimex Related Adverse Events Will be Assessed for Safety by CTCAE v5.0 | 2 Years | Subjects with Ad-RTS-hIL-12 and veledimex related adverse events will be assessed for safety by CTCAE v5.0 |
Countries
United States
Participant flow
Recruitment details
One Arm 2 subject was screened and enrolled but consent was withdrawn prior to Day 0.
Pre-assignment details
All subjects in Arm 1 received 10mg daily of veledimex. A total of three subjects were assigned to Arm 2. One subject withdrew consent prior to any study procedures on Day 0 and received no treatment. A second subject was discontinued from the study due to a Serious Adverse Event (SAE) after the Ad-RTS-hIL-12 injection but prior to receiving veledimex. The third subject received veledimex at a dose of 5 mg/day, which was the body surface area (BSA)-adjusted dose.
Participants by arm
| Arm | Count |
|---|---|
| Arm 1 - Closed Intratumoral Ad-RTS-hIL-12 freehand injection after tumor resection and oral veledimex (activator ligand) in pediatric patients with brain tumors.
Ad-RTS-hIL-12: 2.0 x 10\^11 viral particles (vp) per injection, one intratumoral injection of Ad-RTS-hIL-12
Oral Veledimex - Arm 1 (Pediatric Brain Tumor):
* Planned: 1 dose level (10mg/day) 15 oral daily doses of veledimex
* Actual: All patients received 1 dose level (10 mg/day veledimex) | 3 |
| Arm 2 - Closed Intratumoral Ad-RTS-hIL-12 stereotactic injection and oral veledimex (activator ligand) in pediatric patients with DIPG.
Ad-RTS-hIL-12: 2.0 x 10\^11 viral particles (vp) per injection, one intratumoral injection of Ad-RTS-hIL-12
Oral Veledimex - Arm 2 (DIPG):
* Planned:2 dose levels (10mg/day, 20mg/day)
* Actual: 1 patient received 5 mg/day veledimex. The other patient did not receive veledimex due to SAE. | 2 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Arm 1 - Closed | Arm 2 - Closed | Total |
|---|---|---|---|
| Age, Continuous | 16.1 years | 5.8 years | 12.1 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 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 | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 2 Participants | 1 Participants | 3 Participants |
| Region of Enrollment United States | 3 participants | 2 participants | 5 participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 2 Participants |
| WHO High Grade at Baseline | 3 Participants | 2 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 3 | 1 / 2 |
| other Total, other adverse events | 3 / 3 | 2 / 2 |
| serious Total, serious adverse events | 1 / 3 | 1 / 2 |
Outcome results
Primary
The Safety and Tolerability of Intratumoral Ad-RTS-hIL-12 and Veledimex as Measured by Dose Limiting Toxicities and Compliance.
Dose Limiting Toxicities are defined as events that occur during the first 28 days (Day 0 - Day 28) that meets one of the following criteria: * Any local reaction that requires operative intervention and is felt to be attributable to study drug * Any local reaction that has life-threatening consequences requiring urgent intervention or results in death and is felt to be attributable to study drug * Any Grade 3 or higher non-hematologic adverse event that is at least possibly related to study drug and lasts ≥ 3 days * Nausea and vomiting will not be considered a DLT unless at least Grade 3 and refractory to antiemetics * Grade 3 or higher thrombocytopenia (\< 50,000/mm3) at least possibly related to study drug * Any Grade 4 hematologic toxicity (except thrombocytopenia) that is at least possibly related to study drug and lasts ≥ 5 days * Transient neurological changes are expected in Arm 2 and will not be considered a DLT unless they last \> 10 days
Time frame: From Day 0 through Day 56
Population: The Full Analysis Set (FAS) or the OSP includes every subject who received at least one dose of any study drug recorded in the Data Management (DM) database excluding screen failures.~• The data analysis for Adverse Events or other Safety variables will be performed on the OSP.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm 1 - Closed | The Safety and Tolerability of Intratumoral Ad-RTS-hIL-12 and Veledimex as Measured by Dose Limiting Toxicities and Compliance. | AEs leading to study discontinuation | 0 Participants |
| Arm 1 - Closed | The Safety and Tolerability of Intratumoral Ad-RTS-hIL-12 and Veledimex as Measured by Dose Limiting Toxicities and Compliance. | AE leading to leading to study treatment dose reduction | 0 Participants |
| Arm 1 - Closed | The Safety and Tolerability of Intratumoral Ad-RTS-hIL-12 and Veledimex as Measured by Dose Limiting Toxicities and Compliance. | AE leading to death | 0 Participants |
| Arm 1 - Closed | The Safety and Tolerability of Intratumoral Ad-RTS-hIL-12 and Veledimex as Measured by Dose Limiting Toxicities and Compliance. | Adverse events leading to study treatment dose interruption | 1 Participants |
| Arm 1 - Closed | The Safety and Tolerability of Intratumoral Ad-RTS-hIL-12 and Veledimex as Measured by Dose Limiting Toxicities and Compliance. | AEs leading to study treatment discontinuation | 0 Participants |
| Arm 1 - Closed | The Safety and Tolerability of Intratumoral Ad-RTS-hIL-12 and Veledimex as Measured by Dose Limiting Toxicities and Compliance. | Treatment emergent adverse events | 3 Participants |
| Arm 1 - Closed | The Safety and Tolerability of Intratumoral Ad-RTS-hIL-12 and Veledimex as Measured by Dose Limiting Toxicities and Compliance. | DLTs | 0 Participants |
| Arm 2 - Closed | The Safety and Tolerability of Intratumoral Ad-RTS-hIL-12 and Veledimex as Measured by Dose Limiting Toxicities and Compliance. | Treatment emergent adverse events | 2 Participants |
| Arm 2 - Closed | The Safety and Tolerability of Intratumoral Ad-RTS-hIL-12 and Veledimex as Measured by Dose Limiting Toxicities and Compliance. | DLTs | 1 Participants |
| Arm 2 - Closed | The Safety and Tolerability of Intratumoral Ad-RTS-hIL-12 and Veledimex as Measured by Dose Limiting Toxicities and Compliance. | AE leading to death | 0 Participants |
| Arm 2 - Closed | The Safety and Tolerability of Intratumoral Ad-RTS-hIL-12 and Veledimex as Measured by Dose Limiting Toxicities and Compliance. | AEs leading to study discontinuation | 0 Participants |
| Arm 2 - Closed | The Safety and Tolerability of Intratumoral Ad-RTS-hIL-12 and Veledimex as Measured by Dose Limiting Toxicities and Compliance. | AEs leading to study treatment discontinuation | 1 Participants |
| Arm 2 - Closed | The Safety and Tolerability of Intratumoral Ad-RTS-hIL-12 and Veledimex as Measured by Dose Limiting Toxicities and Compliance. | AE leading to leading to study treatment dose reduction | 0 Participants |
| Arm 2 - Closed | The Safety and Tolerability of Intratumoral Ad-RTS-hIL-12 and Veledimex as Measured by Dose Limiting Toxicities and Compliance. | Adverse events leading to study treatment dose interruption | 1 Participants |
Secondary
Best Overall Response by iRANO Criteria
Best Overall Response was assessed using the immunotherapy Response Assessment for Neuro-Oncology (iRANO) criteria.
Time frame: 2 Years
Population: The Efficacy Evaluable population is defined as all subjects who received at least 1 dose of study drug and had at least one post-treatment tumor assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 1 - Closed | Best Overall Response by iRANO Criteria | Best Tumor Response SD | 0 participants |
| Arm 1 - Closed | Best Overall Response by iRANO Criteria | Best Tumor Response PD | 3 participants |
| Arm 1 - Closed | Best Overall Response by iRANO Criteria | Not Evaluable | 0 participants |
| Arm 2 - Closed | Best Overall Response by iRANO Criteria | Best Tumor Response SD | 2 participants |
| Arm 2 - Closed | Best Overall Response by iRANO Criteria | Best Tumor Response PD | 0 participants |
| Arm 2 - Closed | Best Overall Response by iRANO Criteria | Not Evaluable | 1 participants |
Secondary
Duration of Response (DOR)
Duration of Response (DOR) was defined as the time from the first documentation of a Complete Response (CR) or Partial Response (PR) to the first documentation of Progressive Disease (PD) or death due to any cause, whichever occurred first.
Time frame: From the time of first response (CR or PR) until progression or death
Population: The analysis population for this measure included subjects from the Efficacy Evaluable population who achieved a Complete Response (CR) or Partial Response (PR).
Secondary
Measure Immune Response of Ad-RTS-hIL-12 and Veledimex by a Quantitative Multiplex Immunoassay for Determination of IL-12 and IFNg Levels
Samples for serum cytokine analysis were collected on Days 0, 3, 7, 14, and 28. For the results, participants who had samples analyzed were included in the number analyzed counts; however, values that were below the limit of quantitation (BLQ) were excluded from the calculation of mean and standard deviation.
Time frame: Day 0, Day 3, Day 7, Day 14, and Day 28
Population: The Biomarker Evaluation Population (BEP) includes all subjects who received Ad-RTS-hIL-12 + at least one dose of their cohort-specific dose of veledimex who have adequate biomarker sample(s) at screening (baseline) and at least one non-missing follow-up biomarker assessment, excluding the disqualified assessments. All biomarker related data presentation will be based on the BEP unless specified otherwise. Note: In Arm 2, only 1 subject met this criteria.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 - Closed | Measure Immune Response of Ad-RTS-hIL-12 and Veledimex by a Quantitative Multiplex Immunoassay for Determination of IL-12 and IFNg Levels | Serum IFN-gamma - Day 0 | NA pg/mL | — |
| Arm 1 - Closed | Measure Immune Response of Ad-RTS-hIL-12 and Veledimex by a Quantitative Multiplex Immunoassay for Determination of IL-12 and IFNg Levels | Serum IFN-gamma - Day 3 | 4.4 pg/mL | Standard Deviation 0 |
| Arm 1 - Closed | Measure Immune Response of Ad-RTS-hIL-12 and Veledimex by a Quantitative Multiplex Immunoassay for Determination of IL-12 and IFNg Levels | Serum IFN-gamma - Day 7 | 6.4 pg/mL | Standard Deviation 0 |
| Arm 1 - Closed | Measure Immune Response of Ad-RTS-hIL-12 and Veledimex by a Quantitative Multiplex Immunoassay for Determination of IL-12 and IFNg Levels | Serum IFN-gamma - Day 14 | NA pg/mL | — |
| Arm 1 - Closed | Measure Immune Response of Ad-RTS-hIL-12 and Veledimex by a Quantitative Multiplex Immunoassay for Determination of IL-12 and IFNg Levels | Serum IFN-gamma - Day 28 | NA pg/mL | — |
| Arm 1 - Closed | Measure Immune Response of Ad-RTS-hIL-12 and Veledimex by a Quantitative Multiplex Immunoassay for Determination of IL-12 and IFNg Levels | Serum IL-12 - Day 0 | 12 pg/mL | Standard Deviation 0 |
| Arm 1 - Closed | Measure Immune Response of Ad-RTS-hIL-12 and Veledimex by a Quantitative Multiplex Immunoassay for Determination of IL-12 and IFNg Levels | 1.6Serum IL-12 - Day 3 | 11.1 pg/mL | Standard Deviation 2.1 |
| Arm 1 - Closed | Measure Immune Response of Ad-RTS-hIL-12 and Veledimex by a Quantitative Multiplex Immunoassay for Determination of IL-12 and IFNg Levels | Serum IL-12 - Day 7 | 6.6 pg/mL | Standard Deviation 4.7 |
| Arm 1 - Closed | Measure Immune Response of Ad-RTS-hIL-12 and Veledimex by a Quantitative Multiplex Immunoassay for Determination of IL-12 and IFNg Levels | Serum IL-12 - Day 14 | NA pg/mL | — |
| Arm 1 - Closed | Measure Immune Response of Ad-RTS-hIL-12 and Veledimex by a Quantitative Multiplex Immunoassay for Determination of IL-12 and IFNg Levels | Serum IL-12 - Day 28 | 1.6 pg/mL | Standard Deviation 0 |
| Arm 2 - Closed | Measure Immune Response of Ad-RTS-hIL-12 and Veledimex by a Quantitative Multiplex Immunoassay for Determination of IL-12 and IFNg Levels | Serum IL-12 - Day 7 | NA pg/mL | — |
| Arm 2 - Closed | Measure Immune Response of Ad-RTS-hIL-12 and Veledimex by a Quantitative Multiplex Immunoassay for Determination of IL-12 and IFNg Levels | Serum IFN-gamma - Day 0 | NA pg/mL | — |
| Arm 2 - Closed | Measure Immune Response of Ad-RTS-hIL-12 and Veledimex by a Quantitative Multiplex Immunoassay for Determination of IL-12 and IFNg Levels | Serum IL-12 - Day 0 | NA pg/mL | — |
| Arm 2 - Closed | Measure Immune Response of Ad-RTS-hIL-12 and Veledimex by a Quantitative Multiplex Immunoassay for Determination of IL-12 and IFNg Levels | Serum IFN-gamma - Day 3 | 11.4 pg/mL | Standard Deviation 0 |
| Arm 2 - Closed | Measure Immune Response of Ad-RTS-hIL-12 and Veledimex by a Quantitative Multiplex Immunoassay for Determination of IL-12 and IFNg Levels | Serum IL-12 - Day 28 | NA pg/mL | — |
| Arm 2 - Closed | Measure Immune Response of Ad-RTS-hIL-12 and Veledimex by a Quantitative Multiplex Immunoassay for Determination of IL-12 and IFNg Levels | Serum IFN-gamma - Day 7 | NA pg/mL | — |
| Arm 2 - Closed | Measure Immune Response of Ad-RTS-hIL-12 and Veledimex by a Quantitative Multiplex Immunoassay for Determination of IL-12 and IFNg Levels | 1.6Serum IL-12 - Day 3 | NA pg/mL | — |
| Arm 2 - Closed | Measure Immune Response of Ad-RTS-hIL-12 and Veledimex by a Quantitative Multiplex Immunoassay for Determination of IL-12 and IFNg Levels | Serum IFN-gamma - Day 14 | NA pg/mL | — |
| Arm 2 - Closed | Measure Immune Response of Ad-RTS-hIL-12 and Veledimex by a Quantitative Multiplex Immunoassay for Determination of IL-12 and IFNg Levels | Serum IL-12 - Day 14 | NA pg/mL | — |
| Arm 2 - Closed | Measure Immune Response of Ad-RTS-hIL-12 and Veledimex by a Quantitative Multiplex Immunoassay for Determination of IL-12 and IFNg Levels | Serum IFN-gamma - Day 28 | NA pg/mL | — |
Secondary
Overall Survival (OS)
OS is defined as the duration of time from the first dose of the study drug to the date of death. Subjects were followed for up to 2 years.
Time frame: 2 Years
Population: The Safety Population was defined as all subjects who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 1 - Closed | Overall Survival (OS) | Alive | 0 participants |
| Arm 1 - Closed | Overall Survival (OS) | Unknown | 1 participants |
| Arm 1 - Closed | Overall Survival (OS) | Deceased | 2 participants |
| Arm 2 - Closed | Overall Survival (OS) | Alive | 1 participants |
| Arm 2 - Closed | Overall Survival (OS) | Deceased | 1 participants |
| Arm 2 - Closed | Overall Survival (OS) | Unknown | 0 participants |
Secondary
Subjects With Ad-RTS-hIL-12 and Veledimex Related Adverse Events Will be Assessed for Safety by CTCAE v5.0
Subjects with Ad-RTS-hIL-12 and veledimex related adverse events will be assessed for safety by CTCAE v5.0
Time frame: 2 Years
Population: The Full Analysis Set (FAS) or the OSP includes every subject who received at least one dose of any study drug recorded in the Data Management (DM) database excluding screen failures.~• The data analysis for Adverse Events or other Safety variables will be performed on the OSP.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 1 - Closed | Subjects With Ad-RTS-hIL-12 and Veledimex Related Adverse Events Will be Assessed for Safety by CTCAE v5.0 | WHITE BLOOD CELL COUNT DECREASED (INVESTIGATIONS) | 2 participants |
| Arm 1 - Closed | Subjects With Ad-RTS-hIL-12 and Veledimex Related Adverse Events Will be Assessed for Safety by CTCAE v5.0 | LYMPHOCYTE COUNT DECREASED (INVESTIGATIONS) | 2 participants |
| Arm 1 - Closed | Subjects With Ad-RTS-hIL-12 and Veledimex Related Adverse Events Will be Assessed for Safety by CTCAE v5.0 | VOMITING (GASTROINTESTINAL DISORDERS) | 2 participants |
| Arm 1 - Closed | Subjects With Ad-RTS-hIL-12 and Veledimex Related Adverse Events Will be Assessed for Safety by CTCAE v5.0 | HEADACHE (NERVOUS SYSTEM DISORDERS) | 2 participants |
| Arm 1 - Closed | Subjects With Ad-RTS-hIL-12 and Veledimex Related Adverse Events Will be Assessed for Safety by CTCAE v5.0 | PYREXIA (GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS) | 1 participants |
| Arm 1 - Closed | Subjects With Ad-RTS-hIL-12 and Veledimex Related Adverse Events Will be Assessed for Safety by CTCAE v5.0 | ANAEMIA (BLOOD AND LYMPHATIC SYSTEM DISORDERS) | 2 participants |
| Arm 1 - Closed | Subjects With Ad-RTS-hIL-12 and Veledimex Related Adverse Events Will be Assessed for Safety by CTCAE v5.0 | APHASIA (NERVOUS SYSTEM DISORDERS) | 1 participants |
| Arm 1 - Closed | Subjects With Ad-RTS-hIL-12 and Veledimex Related Adverse Events Will be Assessed for Safety by CTCAE v5.0 | FATIGUE (GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS) | 1 participants |
| Arm 1 - Closed | Subjects With Ad-RTS-hIL-12 and Veledimex Related Adverse Events Will be Assessed for Safety by CTCAE v5.0 | HYPONATRAEMIA (METABOLISM AND NUTRITION DISORDERS) | 2 participants |
| Arm 1 - Closed | Subjects With Ad-RTS-hIL-12 and Veledimex Related Adverse Events Will be Assessed for Safety by CTCAE v5.0 | NAUSEA (GASTROINTESTINAL DISORDERS) | 1 participants |
| Arm 1 - Closed | Subjects With Ad-RTS-hIL-12 and Veledimex Related Adverse Events Will be Assessed for Safety by CTCAE v5.0 | PLATELET COUNT DECREASED (INVESTIGATIONS) | 2 participants |
| Arm 1 - Closed | Subjects With Ad-RTS-hIL-12 and Veledimex Related Adverse Events Will be Assessed for Safety by CTCAE v5.0 | TACHYCARDIA (CARDIAC DISORDERS) | 0 participants |
| Arm 2 - Closed | Subjects With Ad-RTS-hIL-12 and Veledimex Related Adverse Events Will be Assessed for Safety by CTCAE v5.0 | PLATELET COUNT DECREASED (INVESTIGATIONS) | 0 participants |
| Arm 2 - Closed | Subjects With Ad-RTS-hIL-12 and Veledimex Related Adverse Events Will be Assessed for Safety by CTCAE v5.0 | WHITE BLOOD CELL COUNT DECREASED (INVESTIGATIONS) | 2 participants |
| Arm 2 - Closed | Subjects With Ad-RTS-hIL-12 and Veledimex Related Adverse Events Will be Assessed for Safety by CTCAE v5.0 | APHASIA (NERVOUS SYSTEM DISORDERS) | 1 participants |
| Arm 2 - Closed | Subjects With Ad-RTS-hIL-12 and Veledimex Related Adverse Events Will be Assessed for Safety by CTCAE v5.0 | LYMPHOCYTE COUNT DECREASED (INVESTIGATIONS) | 2 participants |
| Arm 2 - Closed | Subjects With Ad-RTS-hIL-12 and Veledimex Related Adverse Events Will be Assessed for Safety by CTCAE v5.0 | NAUSEA (GASTROINTESTINAL DISORDERS) | 1 participants |
| Arm 2 - Closed | Subjects With Ad-RTS-hIL-12 and Veledimex Related Adverse Events Will be Assessed for Safety by CTCAE v5.0 | VOMITING (GASTROINTESTINAL DISORDERS) | 1 participants |
| Arm 2 - Closed | Subjects With Ad-RTS-hIL-12 and Veledimex Related Adverse Events Will be Assessed for Safety by CTCAE v5.0 | FATIGUE (GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS) | 1 participants |
| Arm 2 - Closed | Subjects With Ad-RTS-hIL-12 and Veledimex Related Adverse Events Will be Assessed for Safety by CTCAE v5.0 | HEADACHE (NERVOUS SYSTEM DISORDERS) | 1 participants |
| Arm 2 - Closed | Subjects With Ad-RTS-hIL-12 and Veledimex Related Adverse Events Will be Assessed for Safety by CTCAE v5.0 | TACHYCARDIA (CARDIAC DISORDERS) | 2 participants |
| Arm 2 - Closed | Subjects With Ad-RTS-hIL-12 and Veledimex Related Adverse Events Will be Assessed for Safety by CTCAE v5.0 | PYREXIA (GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS) | 2 participants |
| Arm 2 - Closed | Subjects With Ad-RTS-hIL-12 and Veledimex Related Adverse Events Will be Assessed for Safety by CTCAE v5.0 | HYPONATRAEMIA (METABOLISM AND NUTRITION DISORDERS) | 0 participants |
| Arm 2 - Closed | Subjects With Ad-RTS-hIL-12 and Veledimex Related Adverse Events Will be Assessed for Safety by CTCAE v5.0 | ANAEMIA (BLOOD AND LYMPHATIC SYSTEM DISORDERS) | 0 participants |
Secondary
To Measure the Veledimex in Blood and Brain Tumor by Using the LC-MS Method
Veledimex brain concentration. Veledimex plasma concentration was below the limit of quantitation for most patients. Given the limited number of subjects enrolled and early closure of the study, complete assessment of veledimex in blood and brain tumor could not be determined.
Time frame: From Day 0 through Day 15 of veledimex dosing
Population: Patients with available brain tumor results. Arm 2 patient result was below the level of quantitation (1.8 ng/mL). Arm 1 BLQ was 0.1 ng/mL. One patients was less than BLQ.~Arm 2 patient plasma concentrations were not reported due to bioanalytical non-reproducibility. NRR (Non-Reportable Results) is the actual result reported from the central lab which was due to assay reagent expiration.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Arm 1 - Closed | To Measure the Veledimex in Blood and Brain Tumor by Using the LC-MS Method | Brain tumor results (Day 0) | 0.172 ng/mL |
| Arm 1 - Closed | To Measure the Veledimex in Blood and Brain Tumor by Using the LC-MS Method | Day 1 predose- veledimex plasma PK | 1.02 ng/mL |
| Arm 1 - Closed | To Measure the Veledimex in Blood and Brain Tumor by Using the LC-MS Method | Day 14 predose- veledimex plasma PK | 4.39 ng/mL |
| Arm 1 - Closed | To Measure the Veledimex in Blood and Brain Tumor by Using the LC-MS Method | Day 2 - veledimex plasma PK | 2.09 ng/mL |
| Arm 1 - Closed | To Measure the Veledimex in Blood and Brain Tumor by Using the LC-MS Method | Day 14 2 hr postdose - veledimex plasma PK | 36.83 ng/mL |
| Arm 1 - Closed | To Measure the Veledimex in Blood and Brain Tumor by Using the LC-MS Method | Day 1 2 hr postdose- veledimex plasma PK | 11.64 ng/mL |
| Arm 1 - Closed | To Measure the Veledimex in Blood and Brain Tumor by Using the LC-MS Method | Day 14 4 hr postdose - veledimex plasma PK | 19.80 ng/mL |
| Arm 1 - Closed | To Measure the Veledimex in Blood and Brain Tumor by Using the LC-MS Method | Day 0 time of resection - veledimex plasma PK | 1.40 ng/mL |
| Arm 1 - Closed | To Measure the Veledimex in Blood and Brain Tumor by Using the LC-MS Method | Day 14 6 hr postdose - veledimex plasma PK | 7.63 ng/mL |
| Arm 1 - Closed | To Measure the Veledimex in Blood and Brain Tumor by Using the LC-MS Method | Day 1 4 hr postdose- veledimex plasma PK | 5.66 ng/mL |
| Arm 1 - Closed | To Measure the Veledimex in Blood and Brain Tumor by Using the LC-MS Method | Day 15 24 hr postdose - veledimex plasma PK | 4.35 ng/mL |
| Arm 1 - Closed | To Measure the Veledimex in Blood and Brain Tumor by Using the LC-MS Method | Day 1 6 hr postdose- veledimex plasma PK | 5.64 ng/mL |
| Arm 2 - Closed | To Measure the Veledimex in Blood and Brain Tumor by Using the LC-MS Method | Day 15 24 hr postdose - veledimex plasma PK | NA ng/mL |
| Arm 2 - Closed | To Measure the Veledimex in Blood and Brain Tumor by Using the LC-MS Method | Day 1 6 hr postdose- veledimex plasma PK | NA ng/mL |
| Arm 2 - Closed | To Measure the Veledimex in Blood and Brain Tumor by Using the LC-MS Method | Brain tumor results (Day 0) | NA ng/mL |
| Arm 2 - Closed | To Measure the Veledimex in Blood and Brain Tumor by Using the LC-MS Method | Day 0 time of resection - veledimex plasma PK | NA ng/mL |
| Arm 2 - Closed | To Measure the Veledimex in Blood and Brain Tumor by Using the LC-MS Method | Day 1 predose- veledimex plasma PK | NA ng/mL |
| Arm 2 - Closed | To Measure the Veledimex in Blood and Brain Tumor by Using the LC-MS Method | Day 1 2 hr postdose- veledimex plasma PK | NA ng/mL |
| Arm 2 - Closed | To Measure the Veledimex in Blood and Brain Tumor by Using the LC-MS Method | Day 1 4 hr postdose- veledimex plasma PK | NA ng/mL |
| Arm 2 - Closed | To Measure the Veledimex in Blood and Brain Tumor by Using the LC-MS Method | Day 2 - veledimex plasma PK | NA ng/mL |
| Arm 2 - Closed | To Measure the Veledimex in Blood and Brain Tumor by Using the LC-MS Method | Day 14 predose- veledimex plasma PK | NA ng/mL |
| Arm 2 - Closed | To Measure the Veledimex in Blood and Brain Tumor by Using the LC-MS Method | Day 14 2 hr postdose - veledimex plasma PK | NA ng/mL |
| Arm 2 - Closed | To Measure the Veledimex in Blood and Brain Tumor by Using the LC-MS Method | Day 14 4 hr postdose - veledimex plasma PK | NA ng/mL |
| Arm 2 - Closed | To Measure the Veledimex in Blood and Brain Tumor by Using the LC-MS Method | Day 14 6 hr postdose - veledimex plasma PK | NA ng/mL |