A Study of Ad-RTS-hIL-12 With Veledimex in Combination Wi... | NCT03636477

Label	Type	Description	Intervention Names
Ad-RTS-hIL-12 + veledimex in combination with nivolumab	Experimental	Intratumoral Ad-RTS-hIL-12 and varying doses of oral veledimex (activator ligand) given in combination with nivolumab via infusion.	Biological: Ad-RTS-hIL-12 Drug: veledimex Drug: Nivolumab

Name	Type	Description	Arm Group Labels	Other Names
Ad-RTS-hIL-12	Biological	2.0 x 10^11 viral particles (vp) per injection intratumoral injection of Ad-RTS-hIL-12	Ad-RTS-hIL-12 + veledimex in combination with nivolumab

Measure	Description	Time Frame
Number of Participants With Adverse Events (AEs)	Evaluation of adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.03 will be based on the incidence, intensity and type of adverse event. AEs will be regarded as treatment-emergent adverse events (TEAEs) during the treatment period regardless of relationship to study drug if: • The AE occurred or worsened from baseline during or after administration of the first dose of study drug (on or after Day 0).	2 years and 4 months
Number of Participants With Veledimex Dose Compliance	Evaluation will be based on expected dose compliance. Subjects were instructed to document veledimex dosing compliance in a subject diary, including the time each dose was taken, the time of the last meal prior to administration of veledimex, the number of capsules taken, whether the subject missed any veledimex doses, and reason for any missed doses. Investigational product container(s) with any remaining capsules were returned to the study staff on Day 15, and staff assessed dose compliance.	From Day 0 through Day 14 for each participant

Measure	Description	Time Frame
Number of Participants With a Dose-Limiting Toxicity (DLT)	The primary objective was to determine the Maximum Tolerated Dose (MTD), defined as the dose at which fewer than 33% of subjects experience a Dose-Limiting Toxicity (DLT). The MTD was not reached; a Maximum Administered Dose (MAD) of 20mg veledimex and 3mg/kg nivolumab was determined. This measure reports the number of subjects who experienced a DLT during the first treatment cycle in each dose cohort.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male or female subject ≥18 and ≤75 years of age
Provision of written informed consent for tumor resection, stereotactic surgery, tumor biopsy, samples collection, and treatment with investigational products prior to undergoing any study specific procedures
Histologically confirmed supratentorial glioblastoma
Evidence of tumor recurrence/progression by magnetic resonance imaging (MRI) according to response assessment in neuro-oncology (RANO) criteria after standard initial therapy
Previous standard-of-care antitumor treatment including surgery and/or biopsy and chemoradiation. At the time of registration, subjects must have recovered from the toxic effects of previous treatments as determined by the treating physician. The washout periods from prior therapies are intended as follows: (windows other than what is listed below should be allowed only after consultation with the Medical Monitor)
1. Nitrosureas: 6 weeks
2. Other cytotoxic agents: 4 weeks
3. Antiangiogenic agents, including bevacizumab: 4weeks
4. Targeted agents, including small molecule tyrosine kinase inhibitors: 2 weeks
5. Vaccine-based therapy: 3 months
Able to undergo standard MRI scans with contrast agent before enrollment and after treatment
Karnofsky Performance Status ≥70%
Adequate bone marrow reserves and liver and kidney function, as assessed by the following laboratory requirements:
1. Hemoglobin ≥9 g/L
2. Lymphocytes >500/mm3
3. Absolute neutrophil count ≥1500/mm3
4. Platelets ≥100,000/mm3
5. Serum creatinine ≤1.5 x upper limit of normal (ULN)
6. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 x ULN. For subjects with documented liver metastases, ALT and AST ≤5 x ULN
7. Total bilirubin < 1.5 x ULN
8. International normalized ratio (INR) and activated partial thromboplastin time (aPTT) within normal institutional limits
Male and female subjects must agree to use a highly reliable method of birth control (expected failure rate <5% per year) from the Screening Visit through 28 days after the last dose of study drug. Women of childbearing potential (perimenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential) must have a negative pregnancy test at screening.
Normal cardiac and pulmonary function as evidenced by a normal electrocardiogram (ECG) and peripheral oxygen saturation (SpO2) ≥90% by pulse oximetry

Exclusion Criteria:

Previous treatment with inhibitors of immunocheckpoint pathways (eg, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody) or other agents specifically targeting T cells
Radiotherapy treatment within 4 weeks or less prior to veledimex dosing
Subjects with clinically significant increased intracranial pressure (eg, impending herniation or requirement for immediate palliative treatment) or uncontrolled seizures
Known immunosuppressive disease, or autoimmune conditions, and/or chronic viral infections (eg, human immunodeficiency virus [HIV], hepatitis)
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.
Use of enzyme inducing antiepileptic drugs (EIAED) within 7 days prior to the first dose of study drug. Note: Levetiracetam (Keppra®) is not an EIAED and is allowed.
Other concurrent clinically active malignant disease, requiring treatment, with the exception of non-melanoma cancers of the skin or carcinoma in situ of the cervix or nonmetastatic prostate cancer
Nursing or pregnant females
Prior exposure to veledimex
Use of medications that induce, inhibit, or are substrates of cytochrome p450 (CYP450) 3A4 within 7 days prior to veledimex dosing without consultation with the Medical Monitor
Presence of any contraindication for a neurosurgical procedure
Unstable or clinically significant concurrent medical condition that would, in the opinion of the Investigator or Medical Monitor, jeopardize the safety of a subject and/or their compliance with the protocol. Examples include, but are not limited to: unstable angina, congestive heart failure, myocardial infarction within 2 months of screening, ongoing maintenance therapy for life-threatening ventricular arrhythmia or uncontrolled asthma.
History of myocarditis or congestive heart failure (as defined by New York Heart Association Functional Classification III or IV), as well as unstable angina, serious uncontrolled cardiac arrhythmia, uncontrolled infection, or myocardial infarction 6 months prior to study entry.

Name	Affiliation	Role
Jaymes Holland	Alaunos Therapeutics	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Northwestern Memorial Hospital		Chicago	Illinois	60611	United States
Brigham & Women's Hospital

PubMed Identifier	Type	Citation	Retractions
34850166	Derived	Chiocca EA, Gelb AB, Chen CC, Rao G, Reardon DA, Wen PY, Bi WL, Peruzzi P, Amidei C, Triggs D, Seften L, Park G, Grant J, Truman K, Buck JY, Hadar N, Demars N, Miao J, Estupinan T, Loewy J, Chadha K, Tringali J, Cooper L, Lukas RV. Combined immunotherapy with controlled interleukin-12 gene therapy and immune checkpoint blockade in recurrent glioblastoma: An open-label, multi-institutional phase I trial. Neuro Oncol. 2022 Jun 1;24(6):951-963. doi: 10.1093/neuonc/noab271.

ID	Title	Description
FG000	Veledimex 10mg Dose Level + Nivolumab 1mg/kg	Cohort S1: Ad-RTS-hIL-12 on Day 0 Veledimex 10 mg once daily (QD) on Days 0-14 Nivolumab 1 mg/kg intravenously (IV) over 60 minutes on Day -7, Day 15, and approx every 2 weeks
FG001	Veledimex 10mg Dose Level + Nivolumab 3mg/kg

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jan 23, 2018	Mar 9, 2025

ID	Title	Description
BG000	Veledimex 10mg Dose Level + Nivolumab 1mg/kg	Cohort S1: Ad-RTS-hIL-12 on Day 0 Veledimex 10 mg QD on Days 0-14 Nivolumab 1 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks
BG001	Veledimex 10mg Dose Level + Nivolumab 3mg/kg	Cohort S2: Ad-RTS-hIL-12 on Day 0 Veledimex 10 mg QD on Days 0-14 Nivolumab 3 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks
BG002	Veledimex 20mg Dose Level + Nivolumab 3mg/kg	Cohort S3: Ad-RTS-hIL-12 on Day 0 Veledimex 20 mg QD on Days 0-14 Nivolumab 3 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks
BG003	Total	Total of all reporting groups

Units	Counts
Participants	BG0003 BG0013 BG00215 BG00321

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 Adverse Events (AEs)

Evaluation of adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.03 will be based on the incidence, intensity and type of adverse event.

AEs will be regarded as treatment-emergent adverse events (TEAEs) during the treatment period regardless of relationship to study drug if:

• The AE occurred or worsened from baseline during or after administration of the first dose of study drug (on or after Day 0).

The Full Analysis Set (FAS): Overall Safety Population (OSP) includes all subjects who have received at least one dose of veledimex (pretumor resection and) and/or all subjects who received Ad-RTS-hIL-12.

Posted

Number

participants

2 years and 4 months

ID	Title	Description
OG000	Veledimex 10mg Dose Level + Nivolumab 1mg/kg	Cohort S1: Ad-RTS-hIL-12 on Day 0 Veledimex 10 mg QD on Days 0-14 Nivolumab 1 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks
OG001	Veledimex 10mg Dose Level + Nivolumab 3mg/kg	Cohort S2: Ad-RTS-hIL-12 on Day 0 Veledimex 10 mg QD on Days 0-14 Nivolumab 3 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks
OG002	Veledimex 20mg Dose Level + Nivolumab 3mg/kg	Cohort S3: Ad-RTS-hIL-12 on Day 0 Veledimex 20 mg QD on Days 0-14 Nivolumab 3 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks

Units	Counts
Participants	OG0003 OG0013 OG00215

Title

Denominators

Categories

Any TEAEs

Title	Measurements
	OG0003 OG0013 OG00215

Any Serious TEAEs

Primary

Number of Participants With Veledimex Dose Compliance

Evaluation will be based on expected dose compliance. Subjects were instructed to document veledimex dosing compliance in a subject diary, including the time each dose was taken, the time of the last meal prior to administration of veledimex, the number of capsules taken, whether the subject missed any veledimex doses, and reason for any missed doses. Investigational product container(s) with any remaining capsules were returned to the study staff on Day 15, and staff assessed dose compliance.

Posted

Number

participants

From Day 0 through Day 14 for each participant

ID	Title	Description
OG000	Veledimex 10mg Dose Level + Nivolumab 1mg/kg	Cohort S1: Ad-RTS-hIL-12 on Day 0 Veledimex 10 mg QD on Days 0-14 Nivolumab 1 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks
OG001	Veledimex 10mg Dose Level + Nivolumab 3mg/kg	Cohort S2: Ad-RTS-hIL-12 on Day 0 Veledimex 10 mg QD on Days 0-14 Nivolumab 3 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks
OG002	Veledimex 20mg Dose Level + Nivolumab 3mg/kg

Secondary

Number of Participants With a Dose-Limiting Toxicity (DLT)

The primary objective was to determine the Maximum Tolerated Dose (MTD), defined as the dose at which fewer than 33% of subjects experience a Dose-Limiting Toxicity (DLT). The MTD was not reached; a Maximum Administered Dose (MAD) of 20mg veledimex and 3mg/kg nivolumab was determined. This measure reports the number of subjects who experienced a DLT during the first treatment cycle in each dose cohort.

Posted

Number

participants

The first treatment cycle (21 days).

ID	Title	Description
OG000	Veledimex 10mg DoseLevel + Nivolumab1mg/kg	Cohort S1: Ad-RTS-hIL-12 on Day0 Veledimex 10 mg QD on Days 0-14 Nivolumab 1 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks
OG001	Veledimex 10mg Dose Level + Nivolumab 3mg/kg	Cohort S2: Ad-RTS-hIL-12 on Day0 Veledimex 10 mg QD on Days 0-14Nivolumab 3 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks
OG002	Veledimex 20mg Dose Level + Nivolumab 3mg/kg

Secondary

Tumor Objective Response Rate (ORR)

To determine investigator assessment of response including tumor ORR of Ad-RTS-hIL-12 + veledimex when administered in combination with nivolumab. Investigator assessment of ORR was determined according to Immunotherapy Response Assessment in Neuro-Oncology (iRANO) criteria. iRANO is a set of criteria built on RANO criteria but adapts them for immune-related effects to evaluate treatment response in brain tumor patients receiving immunotherapy. It addresses unique challenges like pseudoprogression, where immune-related inflammation mimics tumor growth on imaging allowing continued treatment despite early radiographic worsening if the patient is clinically stable. This criteria requires confirmation of progression with follow-up imaging ≥3 months later, especially within the first 6 months of immunotherapy.

The Evaluable Safety Population (ESP) includes subjects who have received Ad-RTS-hIL-12 and at least one dose of veledimex after Ad-RTS-hIL-12 administration. The ESP will be evaluated for investigator assessment of objective response rate (ORR).

Posted

Count of Participants

Participants

2 years and 4 months

ID	Title	Description
OG000	Veledimex 10mg Dose Level + Nivolumab 1mg/kg	Cohort S1: Ad-RTS-hIL-12 on Day 0 Veledimex 10 mg QD on Days 0-14 Nivolumab 1 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks
OG001	Veledimex 10mg Dose Level + Nivolumab 3mg/kg	Cohort S2: Ad-RTS-hIL-12 on Day 0 Veledimex 10 mg QD on Days 0-14 Nivolumab 3 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks

Secondary

Progression Free Survival (PFS)

PFS is the time in days from the first treatment (either veledimex or Ad-RTS-hIL-12) to the first assessment on which the overall response is reported as disease progression (per Response Assessment in Neuro-Oncology [RANO] or Immunotherapy Response Assessment in Neuro-Oncology [iRANO] criteria). Subjects withdrawing from the study will be censored at their last non progressive disease response assessment. If a subject does not have a non-progressive disease response assessment, the subject will be censored on the date of the first treatment as described above.

Posted

Mean

Standard Deviation

Days

2 years and 4 months

ID	Title	Description
OG000	Veledimex 10mg Dose Level + Nivolumab 1mg/kg	Cohort S1: Ad-RTS-hIL-12 on Day 0 Veledimex 10 mg QD on Days 0-14 Nivolumab 1 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks
OG001	Veledimex 10mg Dose Level + Nivolumab 3mg/kg	Cohort S2: Ad-RTS-hIL-12 on Day 0 Veledimex 10 mg QD on Days 0-14 Nivolumab 3 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks
OG002	Veledimex 20mg Dose Level + Nivolumab 3mg/kg

Secondary

Rate of Pseudo-progression (PSP)

PSP -- Progression free survival was originally defined for determination of PSP requiring confirmation of progression (per Response Assessment in Neuro-Oncology [RANO] or Immunotherapy Response Assessment in Neuro-Oncology [iRANO] criteria).

The Evaluable Safety Population (ESP) includes subjects who have received Ad-RTS-hIL-12 and at least one dose of veledimex after Ad-RTS-hIL-12 administration. The ESP is denoted as the PP population in this uncontrolled setting.

Posted

Number

participants

2 years and 4 months

ID	Title	Description
OG000	Veledimex 10mg Dose Level + Nivolumab 1mg/kg	Cohort S1: Ad-RTS-hIL-12 on Day 0 Veledimex 10 mg QD on Days 0-14 Nivolumab 1 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks
OG001	Veledimex 10mg Dose Level + Nivolumab 3mg/kg	Cohort S2: Ad-RTS-hIL-12 on Day 0 Veledimex 10 mg QD on Days 0-14 Nivolumab 3 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks
OG002	Veledimex 20mg Dose Level + Nivolumab 3mg/kg	Cohort S3: Ad-RTS-hIL-12 on Day 0 Veledimex 20 mg QD on Days 0-14 Nivolumab 3 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks

Secondary

Overall Survival (OS)

The percentage of participants alive at each time point (6, 9, 12, 15, 18, and 24 months) are reported.

The Overall Safety Population (OSP) included all subjects who received at least one dose of any study drug.

Posted

Number

Percentage of participants

Up to 24 months

ID	Title	Description
OG000	Veledimex 10mg Dose Level + Nivolumab 1mg/kg	Cohort S1: Ad-RTS-hIL-12 on Day 0 Veledimex 10 mg QD on Days 0-14 Nivolumab 1 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks
OG001	Veledimex 10mg Dose Level + Nivolumab 3mg/kg	Cohort S2: Ad-RTS-hIL-12 on Day 0 Veledimex 10 mg QD on Days 0-14 Nivolumab 3 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks
OG002	Veledimex 20mg Dose Level + Nivolumab 3mg/kg	Cohort S3: Ad-RTS-hIL-12 on Day 0 Veledimex 20 mg QD on Days 0-14 Nivolumab 3 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks

Units	Counts

Secondary

Changes From Baseline in Cellular Responses Elicited by Ad-RTS-hIL-12 and Veledimex in Combination With Nivolumab.

Blood samples for pharmacodynamic biomarker evaluation were collected at screening, during treatment, and post-treatment. The immunological and biological response markers include serum cytokines (IL-12 and IFNℽ), and T and B cell subpopulations. Serum IL-12 and downstream IFNℽ expressions are reported by time point.

Evaluable Safety Population (ESP) includes subjects who have received nivolumab, Ad-RTS-hIL-12, and at least one dose of veledimex. Pharmacodynamic Population (PDP) refers to ESP.

Posted

Mean

Standard Deviation

pg/mL

From Screening through Day 28, assessed at Screening and Days 0, 1, 3, 7, 14, and 28

ID	Title	Description
OG000	Veledimex 10mg Dose Level + Nivolumab 1mg/kg	Cohort S1: Ad-RTS-hIL-12 on Day 0 Veledimex 10 mg QD on Days 0-14 Nivolumab 1 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks
OG001	Veledimex 10mg Dose Level + Nivolumab 3mg/kg	Cohort S2: Ad-RTS-hIL-12 on Day 0 Veledimex 10 mg QD on Days 0-14 Nivolumab 3 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks
OG002	Veledimex 20mg Dose Level + Nivolumab 3mg/kg

Secondary

Changes From Baseline in Humoral Immune Responses Elicited by Ad-RTS-hIL-12 and Veledimex in Combination With Nivolumab.

Blood samples for pharmacodynamic biomarker evaluation were collected at screening, during treatment, and post-treatment.

Whole blood flow cytometry was used to assess the circulating blood cell subpopulations (e.g., T-reg and T cell panels).

Evaluable Safety Population (ESP) includes subjects who have received nivolumab, Ad-RTS-hIL-12, and at least one dose of veledimex. Pharmacodynamic Population (PDP) refers to ESP.

Posted

Mean

Standard Deviation

percentage

From Screening through Day 28, assessed at Screening, Days 0, 14, and 28

ID	Title	Description
OG000	Combined: Veledimex 10mg Dose Level + Nivolumab 1mg/kg	Cohort S1: Ad-RTS-hIL-12 on Day 0 Veledimex 10 mg QD on Days 0-14 Nivolumab 1 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks
OG001	Veledimex 10mg Dose Level + Nivolumab 3mg/kg	Cohort S2: Ad-RTS-hIL-12 on Day 0 Veledimex 10 mg QD on Days 0-14 Nivolumab 3 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks
OG002	Veledimex 20mg Dose Level + Nivolumab 3mg/kg	Cohort S3: Ad-RTS-hIL-12 on Day 0 Veledimex 20 mg QD on Days 0-14 Nivolumab 3 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks

Secondary

Veledimex Pharmacokinetic Profile: Maximum Plasma Concentration (Cmax)

Cmax was determined from the maximum plasma concentration from Day 0 (post veledimex and resection/craniotomy), 3-5 hours after the veledimex dose on Day 1, and 3-5 hours after the veledimex dose on Day 14.

All subjects with available plasma-time concentration data are included in the PK Population.

Posted

Mean

Standard Deviation

ng/mL

Day 0 to Day 15 (Day 14 24-hour post dose)

ID	Title	Description
OG000	Veledimex 10mg Dose Level + Nivolumab 1mg/kg	Cohort S1: Ad-RTS-hIL-12 on Day 0 Veledimex 10 mg QD on Days 0-14 Nivolumab 1 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks Cohort S2: Ad-RTS-hIL-12 on Day 0 Veledimex 10 mg QD on Days 0-14 Nivolumab 3 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks
OG001	Veledimex 10mg Dose Level + Nivolumab 3mg/kg	Cohort S2: Ad-RTS-hIL-12 on Day 0 Veledimex 10 mg QD on Days 0-14 Nivolumab 3 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks
OG002	Veledimex 20mg Dose Level + Nivolumab 3mg/kg	Cohort S3: Ad-RTS-hIL-12 on Day 0 Veledimex 20 mg QD on Days 0-14 Nivolumab 3 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks

Secondary

Veledimex Pharmacokinetic Profile: Time to Maximum Plasma Concentration (Tmax)

Tmax was determined from the time of maximum plasma concentration from Day 0 (post veledimex and resection/craniotomy), 3-5 hours after the veledimex dose on Day 1, and 3-5 hours after the veledimex dose on Day 14.

All subjects with available plasma-time concentration data are included in the PK Population.

Posted

Mean

Standard Deviation

Hours

Day 0 to Day 15 (Day 14 24-hour post dose)

ID	Title	Description
OG000	Combined: Veledimex 10mg Dose Level + Nivolumab 1mg/kg & 3mg/kg	Cohort S1: Ad-RTS-hIL-12 on Day 0 Veledimex 10 mg QD on Days 0-14 Nivolumab 1 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks
OG001	Veledimex 10mg Dose Level + Nivolumab 3mg/kg	Cohort S2: Ad-RTS-hIL-12 on Day 0 Veledimex 10 mg QD on Days 0-14 Nivolumab 3 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks
OG002	Veledimex 20mg Dose Level + Nivolumab 3mg/kg	Cohort S3: Ad-RTS-hIL-12 on Day 0 Veledimex 20 mg QD on Days 0-14 Nivolumab 3 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks

Secondary

Veledimex Pharmacokinetic Profile: Half-life (t1/2)

t1/2 was determined from the plasma concentrations measured from Day 0 (post veledimex and resection/craniotomy) through Day 15 (24 hours post Day 14 dose)

All subjects with available plasma-time concentration data are included in the PK Population.

Posted

Mean

Standard Deviation

hours

Day 0 to Day 15 (24 hours post Day 14 dose)

ID	Title	Description
OG000	Veledimex 10mg Dose Level + Nivolumab 1mg/kg	Cohort S1: Ad-RTS-hIL-12 on Day 0 Veledimex 10 mg QD on Days 0-14 Nivolumab 1 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks
OG001	Veledimex 10mg Dose Level + Nivolumab 3mg/kg	Cohort S2: Ad-RTS-hIL-12 on Day 0 Veledimex 10 mg QD on Days 0-14 Nivolumab 3 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks
OG002	Veledimex 20mg Dose Level + Nivolumab 3mg/kg	Cohort S3: Ad-RTS-hIL-12 on Day 0 Veledimex 20 mg QD on Days 0-14 Nivolumab 3 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks

Secondary

Veledimex Pharmacokinetic Profile: Area Under the Concentration-versus-time Curve (AUC)

AUC was determined from the plasma concentrations measured from Day 0 (post veledimex and resection/craniotomy) through Day 15 (24 hours post Day 14 dose)

All Subjects with available plasma-time concentration data are included in the PK Population.

Posted

Mean

Standard Deviation

ng*hr/mL

Day 0 to Day 15 (Day 14 24-hour post dose)

ID	Title	Description
OG000	Veledimex 10mg Dose Level + Nivolumab 1mg/kg	Cohort S1: Ad-RTS-hIL-12 on Day 0 Veledimex 10 mg QD on Days 0-14 Nivolumab 1 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks Cohort S2: Ad-RTS-hIL-12 on Day 0 Veledimex 10 mg QD on Days 0-14 Nivolumab 3 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks
OG001	Veledimex 10mg Dose Level + Nivolumab 3mg/kg	Cohort S2: Ad-RTS-hIL-12 on Day 0 Veledimex 10 mg QD on Days 0-14 Nivolumab 3 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks
OG002	Veledimex 20mg Dose Level + Nivolumab 3mg/kg	Cohort S3: Ad-RTS-hIL-12 on Day 0 Veledimex 20 mg QD on Days 0-14 Nivolumab 3 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks

Secondary

Veledimex Pharmacokinetic Profile: Volume of Distribution (Vd)

Vd was determined from the plasma concentrations measured from Day 0 (post veledimex and resection/craniotomy) through Day 15 (24 hours post Day 14 dose).

All subjects with available plasma-time concentration data are included in the PK Population.

Posted

Mean

Standard Deviation

Day 0 to Day 15 (Day 14 24-hour post dose)

ID	Title	Description
OG000	Veledimex 10mg Dose Level + Nivolumab 1mg/kg	Cohort S1: Ad-RTS-hIL-12 on Day 0 Veledimex 10 mg QD on Days 0-14 Nivolumab 1 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks
OG001	Veledimex 10mg Dose Level + Nivolumab 3mg/kg	Cohort S2: Ad-RTS-hIL-12 on Day 0 Veledimex 10 mg QD on Days 0-14 Nivolumab 3 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks
OG002	Veledimex 20mg Dose Level + Nivolumab 3mg/kg	Cohort S3: Ad-RTS-hIL-12 on Day 0 Veledimex 20 mg QD on Days 0-14 Nivolumab 3 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks

Secondary

Veledimex Pharmacokinetic Profile: Clearance (CL)

CL was determined from the plasma concentrations measured from Day 0 (post veledimex and resection/craniotomy) through Day 15 (24 hours post Day 14 dose).

All subjects with available plasma-time concentration data are included in the PK Population.

Posted

Mean

Standard Deviation

L/hour

Day 0 to Day 15 (Day 14 24-hour post dose)

ID	Title	Description
OG000	Veledimex 10mg Dose Level + Nivolumab 1mg/kg	Cohort S1: Ad-RTS-hIL-12 on Day 0 Veledimex 10 mg QD on Days 0-14 Nivolumab 1 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks
OG001	Veledimex 10mg Dose Level + Nivolumab 3mg/kg	Cohort S2: Ad-RTS-hIL-12 on Day 0 Veledimex 10 mg QD on Days 0-14 Nivolumab 3 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks
OG002	Veledimex 20mg Dose Level + Nivolumab 3mg/kg	Cohort S3: Ad-RTS-hIL-12 on Day 0 Veledimex 20 mg QD on Days 0-14 Nivolumab 3 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks

Secondary

Veledimex Concentration Ratio Between the Brain Tumor and the Blood.

Tumor/plasma ratio at Day 0 by cohort

All subjects with available tumor concentration data are included in the PK Population for determination of tumor/plasma concentration ratio.

Posted

Mean

Standard Deviation

ratio

1 day (Day 0 at time of resection)

ID	Title	Description
OG000	Veledimex 10mg Dose Level + Nivolumab 1mg/kg	Cohort S1: Ad-RTS-hIL-12 on Day 0 Veledimex 10 mg QD on Days 0-14 Nivolumab 1 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks
OG001	Veledimex 10mg Dose Level + Nivolumab 3mg/kg	Cohort S2: Ad-RTS-hIL-12 on Day 0 Veledimex 10 mg QD on Days 0-14 Nivolumab 3 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks
OG002	Veledimex 20mg Dose Level + Nivolumab 3mg/kg	Cohort S3: Ad-RTS-hIL-12 on Day 0 Veledimex 20 mg QD on Days 0-14 Nivolumab 3 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks

Secondary

Cumulative Dexamethasone Use During Days 0-14

To assess concomitant corticosteroid use during the first treatment cycle, the cumulative dose of dexamethasone administered to each subject from Day 0 to Day 14 was calculated. This measure reports the mean cumulative dose in milligrams (mg) for each cohort

The Overall Safety Population (OSP) includes all subjects who have received at least one dose of veledimex and/or Ad-RTS-hIL-12

Posted

Mean

Standard Deviation

Days 0 through 14

ID	Title	Description
OG000	Veledimex 10mg Dose Level + Nivolumab 1mg/kg	Cohort S1: Ad-RTS-hIL-12 on Day 0 Veledimex 10 mg QD on Days 0-14 Nivolumab 1 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks
OG001	Veledimex 10mg Dose Level + Nivolumab 3mg/kg	Cohort S2: Ad-RTS-hIL-12 on Day 0 Veledimex 10 mg QD on Days 0-14 Nivolumab 3 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks
OG002	Veledimex 20mg Dose Level + Nivolumab 3mg/kg	Cohort S3: Ad-RTS-hIL-12 on Day 0 Veledimex 20 mg QD on Days 0-14 Nivolumab 3 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Headache	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0003 events2 affected3 at risk EG0014 events3 affected3 at risk EG00215 events13 affected15 at risk
Seizure	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0002 events1 affected3 at risk EG0010 events0 affected3 at risk EG0027 events3 affected15 at risk
Hemiparesis	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected3 at risk EG0011 events1 affected3 at risk EG00210 events5 affected15 at risk
Aphasia	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0002 events1 affected3 at risk EG0012 events2 affected3 at risk EG0024 events2 affected15 at risk
Dysarthria	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected3 at risk EG0011 events1 affected3 at risk EG0022 events1 affected15 at risk
Cognitive Disorder	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0023 events2 affected15 at risk
Facial Paresis	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected3 at risk EG0022 events1 affected15 at risk
Hemianopia Homonymous	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG0021 events1 affected15 at risk
Neurologic Neglect Syndrome	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0022 events2 affected15 at risk
Visual Field Defect	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG0021 events1 affected15 at risk
Apraxia	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected15 at risk
Cerebrospinal Fluid Leakage	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected15 at risk
Dizziness	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected15 at risk
Haemorrhage Intracranial	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected15 at risk
Lethargy	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected15 at risk
Nystagmus	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected15 at risk
Paraesthesia	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected15 at risk
Quadrantanopia	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected15 at risk
Lymphocyte Count Decreased	Investigations	MedDRA 23.0	Systematic Assessment	EG0004 events2 affected3 at risk EG0012 events2 affected3 at risk EG00220 events9 affected15 at risk
White Blood Cell Count Decreased	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0016 events2 affected3 at risk EG00210 events5 affected15 at risk
Alanine Aminotransferase Increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0003 events1 affected3 at risk EG0010 events0 affected3 at risk EG0025 events4 affected15 at risk
Aspartate Aminotransferase Increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected3 at risk EG0025 events4 affected15 at risk
Lipase Increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0013 events1 affected3 at risk EG0022 events2 affected15 at risk
Blood Bilirubin Increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0024 events3 affected15 at risk
Neutrophil Count Decreased	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0013 events1 affected3 at risk EG0023 events2 affected15 at risk
Blood Alkaline Phosphatase Increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG0022 events2 affected15 at risk
Platelet Count Decreased	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG0022 events2 affected15 at risk
Amylase Increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0014 events1 affected3 at risk EG0022 events1 affected15 at risk
Body Temperature Increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected15 at risk
Weight Decreased	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0022 events2 affected15 at risk
Blood Pressure Increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0022 events1 affected15 at risk
International Normalised Ratio Increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected15 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0002 events2 affected3 at risk EG0013 events2 affected3 at risk EG0023 events3 affected15 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0013 events2 affected3 at risk EG0024 events4 affected15 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0002 events1 affected3 at risk EG0011 events1 affected3 at risk EG0022 events2 affected15 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0002 events1 affected3 at risk EG0011 events1 affected3 at risk EG0022 events2 affected15 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0025 events3 affected15 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected3 at risk EG0012 events2 affected3 at risk EG0021 events1 affected15 at risk
Decreased Appetite	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0022 events2 affected15 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0022 events2 affected15 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected15 at risk
Nausea	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected3 at risk EG0011 events1 affected3 at risk EG0028 events8 affected15 at risk
Constipation	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0002 events2 affected3 at risk EG0010 events0 affected3 at risk EG0026 events5 affected15 at risk
Vomiting	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0022 events2 affected15 at risk
Abdominal Pain	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0012 events1 affected3 at risk EG0020 events0 affected15 at risk
Dry Mouth	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected15 at risk
Pyrexia	General disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected3 at risk EG0018 events1 affected3 at risk EG00211 events5 affected15 at risk
Fatigue	General disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected3 at risk EG0011 events1 affected3 at risk EG0024 events4 affected15 at risk
Pain	General disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected15 at risk
Oedema Peripheral	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected15 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected3 at risk EG0015 events2 affected3 at risk EG0029 events6 affected15 at risk
Muscular Weakness	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected15 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG0020 events0 affected15 at risk
Back Pain	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0022 events2 affected15 at risk
Muscle Spasms	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected15 at risk
Neck Pain	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected15 at risk
Confusional State	Psychiatric disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected3 at risk EG0023 events3 affected15 at risk
Insomnia	Psychiatric disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0022 events2 affected15 at risk
Anxiety	Psychiatric disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected15 at risk
Delirium	Psychiatric disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected15 at risk
Depression	Psychiatric disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected15 at risk
Flat Affect	Psychiatric disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected15 at risk
Personality Change	Psychiatric disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected15 at risk
Rash Maculo-Papular	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0002 events1 affected3 at risk EG0012 events2 affected3 at risk EG0020 events0 affected15 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0023 events3 affected15 at risk
Dry Skin	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected15 at risk
Night Sweats	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG0020 events0 affected15 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected15 at risk
Hypertension	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected3 at risk EG0024 events4 affected15 at risk
Hypotension	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected15 at risk
Urinary Tract Infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG0020 events0 affected15 at risk
Cellulitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected15 at risk
Sinusitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected15 at risk
Wound Infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected15 at risk
Procedural Headache	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected15 at risk
Procedural Pain	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected15 at risk
Urethral Pain	Renal and urinary disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG0022 events1 affected15 at risk
Pollakiuria	Renal and urinary disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0022 events2 affected15 at risk
Urinary Incontinence	Renal and urinary disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected15 at risk
Haematuria	Renal and urinary disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0012 events2 affected3 at risk EG0020 events0 affected15 at risk
Proteinuria	Renal and urinary disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0012 events2 affected3 at risk EG0020 events0 affected15 at risk
Urinary Retention	Renal and urinary disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected15 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected15 at risk
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected15 at risk
Nasal Congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected15 at risk
Oropharyngeal Pain	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected15 at risk
Hypothyroidism	Endocrine disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0022 events2 affected15 at risk
Cytokine Release Syndrome	Immune system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected15 at risk
Ventricular Arrhythmia	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected15 at risk
Hypoacusis	Ear and labyrinth disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected15 at risk
Erectile Dysfunction	Reproductive system and breast disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected3 at risk EG0020 events0 affected15 at risk
Brain Oedema	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0021 events1 affected15 at risk
Hypersensitivity	Immune system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected3 at risk EG0022 events2 affected15 at risk
Skin Infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected3 at risk EG0020 events0 affected15 at risk

ID	Term
D001254	Astrocytoma
D005910	Glioma
D018302	Neoplasms, Neuroepithelial
D017599	Neuroectodermal Tumors
D009373	Neoplasms, Germ Cell and Embryonal
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D009375	Neoplasms, Glandular and Epithelial
D009380	Neoplasms, Nerve Tissue

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Veledimex 10mg Dose Level + Nivolumab 1mg/kg	Cohort S1: Ad-RTS-hIL-12 on Day 0 Veledimex 10 mg QD on Days 0-14 Nivolumab 1 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks	3	3	1	3	3	3
EG001	Veledimex 10mg Dose Level + Nivolumab 3mg/kg	Cohort S2: Ad-RTS-hIL-12 on Day 0 Veledimex 10 mg QD on Days 0-14 Nivolumab 3 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks	3	3	2	3	3	3
EG002	Veledimex 20mg Dose Level + Nivolumab 3mg/kg	Cohort S3: Ad-RTS-hIL-12 on Day 0 Veledimex 20 mg QD on Days 0-14 Nivolumab 3 mg/kg IV over 60 minutes on Day -7, Day 15, and approx every 2 weeks	15	15	6	15	15	15