Metastatic Melanoma, Neoplasm, Skin Cancer
Conditions
Keywords
metastatic melanoma, ADI, ADI-PEG 20, ADI SS PEG 20,000mw, arginine, enzyme therapy
Brief summary
This was a phase 1/2, open-label, dose-escalation study of arginine deiminase linked via succinimidyl succinate to polyethylene glycol of 20,000 molecular weight (ADI-PEG 20) in subjects with advanced melanoma. ADI-PEG 20 was administered intramuscularly (IM) at escalating doses weekly for 9 weeks (cycle 1) or 8 weeks (subsequent cycles). The primary objectives were to the establish the safety, tolerability, and clinical efficacy of ADI-PEG 20. Secondary objectives included evaluation of the metabolic activity by \[18F\]-fluorodeoxyglucose positron emission tomography (FDG PET), pharmacodynamics, correlation of immunogenicity with clinical response, and correlation of argininosuccinate synthetase (ASS) tumor expression with clinical response.
Detailed description
A 3+3 design was implemented during phase 1, in which 3 to 6 subjects were enrolled sequentially into the following escalating dose cohorts: * Cohort 1 (40 IU/m\^2) * Cohort 2 (80 IU/m\^2) * Cohort 3 (160 IU/m\^2) Subjects were monitored for dose-limiting toxicity (DLT) during the first 2 weeks of cycle 1, with DLT defined as any grade 3 or higher toxicity. The maximum tolerated dose (MTD) was defined as the cohort in which \< 33% of subjects (ie, 0/3 or 1/6 subjects in a cohort) experienced DLT. In phase 2, the MTD cohort was expanded in up to 25 patients. Subjects who completed treatment in cycle 1 without DLT were eligible to initiate cycle 2 at week 10 provided that a computed tomography (CT) scan showed either enlargement of existing disease without accompanying symptoms OR stable disease or improvement with no unacceptable toxicity. The same radiologic criteria applied for initiation of subsequent cycles. Subjects could continue to receive study treatment until disease progression.
Interventions
DRUGADI PEG 20
Intramuscular injections were administered into the deltoid, gluteal, or quadricep muscles once weekly (± 2 days) for 9 weeks during cycle 1 and 8 weeks during subsequent cycles
Sponsors
Memorial Sloan Kettering Cancer Center
NYU Langone Health
Ludwig Institute for Cancer Research
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically confirmed malignant melanoma, American Joint Committee on Cancer (AJCC) stage III (unresectable) or IV. Subjects with uveal and mucosal melanomas were eligible. 2. Measurable disease using the Response Evaluation Criteria in Solid Tumors (RECIST). 3. Pathology slides reviewed by the Memorial Hospital Department of Pathology or New York University (NYU) Department of Pathology for confirmation of melanoma diagnosis. 4. Karnofsky performance status of 80% or more. 5. Adequate organ and marrow function, as defined below: * white blood cell count ≥ 3000/µL * absolute neutrophil count ≥ 1500/µL * platelet count ≥ 100,000/µL * total bilirubin ≤ 2.5 x institutional upper limit of normal (ULN) * lactate dehydrogenase ≤ 1.5 x institutional ULN * albumin ≥ 3.0 mg/dL * creatinine ≤ 2.0 mg/dL 6. Expected survival of at least 3 months. 7. Age ≥ 18 years. 8. Able and willing to give valid written informed consent.
Exclusion criteria
1. Receipt of chemotherapy, immunotherapy, or radiotherapy within 3 weeks prior to first dosing of study agent or lack of recovery from adverse events (AEs) due to agents administered more than 3 weeks earlier. For nitrosoureas, at least 6 weeks must have elapsed. 2. Any other malignancy that required concomitant therapy. 3. Any medical condition that could have made it difficult for the subject to complete the full course of treatments, at the discretion of the Principal Investigator or co-Principal Investigators. 4. Metastatic disease to the central nervous system, unless treated and stable. 5. Known human immunodeficiency virus (HIV) positivity. 6. Mental impairment that may have compromised the ability to give informed consent and comply with the requirements of the study. 7. Lack of availability for clinical follow-up assessments. 8. Participation in any other clinical trial involving another investigational agent within 3 weeks prior to enrollment. 9. Pregnant women or women who were nursing. Women of child-bearing potential and sexually active men must have used appropriate contraception during the course of this study. Women of child-bearing potential must not have been pregnant (negative β human chorionic gonadotropin within 2 weeks of treatment) or nursing during treatment. 10. History of seizure disorder.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of Safety and Tolerability of ADI-PEG 20 | Every 1 to 2 weeks for up to 12 months | Analysis of treatment-emergent adverse events (TEAEs) reported from clinical laboratory tests, physical examinations, and vital signs. |
| Best Overall Clinical Tumor Response | Every 8 to 9 weeks for up to 12 months | Clinical tumor responses were evaluated using disease imaging (CT preferred) performed at baseline and at the end of every cycle. Responses were categorized according to RECIST. Per RECIST for target lesions and assessed by MRI: Complete Response (CR): Disappearance of all target lesions \[no evidence of disease\]; Partial Response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD): ≥ 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD): small changes that do not meet above criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Summary of Plasma Arginine Levels Over Time | Up to 9 months | Blood samples were collected at baseline, day 1 (pre-injection), day 4, day 8, and every 7 days thereafter for plasma arginine levels. |
| Summary of Plasma Citrulline Levels Over Time | Up to 9 months | Blood samples were collected at baseline, day 1 (pre-injection), day 4, day 8, and every 7 days thereafter for plasma citrulline levels. |
| Metabolic Tumor Response | Every 8 to 9 weeks for up to 12 months | Metabolic tumor responses were evaluated using fluorodeoxyglucose (FDG) positron emission tomography (PET) at baseline, on day 4, and at the end of every cycle. |
| Correlation Between ASS Tumor Expression and Clinical Response | Up to 12 months | Expression of ASS was analyzed by immunohistochemistry in tumor samples (archived or biopsy) at baseline and compared with overall best clinical response per RECIST. ASS tumor expression is categorized as either negative or ≤ 5% positive tumor cells. |
| Summary of ADI-PEG 20 Immunogenicity Over Time | Up to 12 months | Blood samples were collected at baseline, day 1 (pre-injection), day 4, day 8, and every 7 days thereafter for detection of anti-ADI antibodies. |
| Summary of ADI-PEG 20 Plasma Concentrations Over Time | Up to 12 months | Blood samples were collected on day 1 (pre-injection), day 4, day 8, and every 7 days thereafter for ADI-PEG 20 plasma concentrations. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week Includes subjects enrolled to receive 40 IU/m\^2/week of ADI-PEG 20 | 6 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week Includes subjects enrolled to receive 80 IU/m\^2/week of ADI-PEG 20 | 6 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week Includes subjects enrolled to receive 160 IU/m\^2/week of ADI-PEG 20 | 19 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Progressive disease | 0 | 3 | 4 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Total |
|---|---|---|---|---|
| Age, Continuous | 61.7 years STANDARD_DEVIATION 18.2 | 61.2 years STANDARD_DEVIATION 14.7 | 67.2 years STANDARD_DEVIATION 11.2 | 64.9 years STANDARD_DEVIATION 13.2 |
| ASS Assay Result ≤5% positive | 2 participants | 0 participants | 3 participants | 5 participants |
| ASS Assay Result Negative | 4 participants | 6 participants | 14 participants | 24 participants |
| ASS Assay Result Not done | 0 participants | 0 participants | 2 participants | 2 participants |
| BMI | 22.0 kg/m^2 STANDARD_DEVIATION 4.1 | 24.7 kg/m^2 STANDARD_DEVIATION 1.8 | 26.9 kg/m^2 STANDARD_DEVIATION 4.7 | 25.5 kg/m^2 STANDARD_DEVIATION 4.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 6 Participants | 17 Participants | 29 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 6 Participants | 18 Participants | 30 Participants |
| Sex: Female, Male Female | 5 Participants | 3 Participants | 6 Participants | 14 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 13 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 1 / 19 |
| other Total, other adverse events | 6 / 6 | 6 / 6 | 19 / 19 |
| serious Total, serious adverse events | 4 / 6 | 1 / 6 | 6 / 19 |
Outcome results
Primary
Assessment of Safety and Tolerability of ADI-PEG 20
Analysis of treatment-emergent adverse events (TEAEs) reported from clinical laboratory tests, physical examinations, and vital signs.
Time frame: Every 1 to 2 weeks for up to 12 months
Population: Safety Analysis Set (all subjects who received at least 1 dose of ADI-PEG 20)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Assessment of Safety and Tolerability of ADI-PEG 20 | Grade 4 TEAE | 0 participants |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Assessment of Safety and Tolerability of ADI-PEG 20 | TEAE leading to withdrawal | 0 participants |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Assessment of Safety and Tolerability of ADI-PEG 20 | Treatment-related TEAE | 5 participants |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Assessment of Safety and Tolerability of ADI-PEG 20 | Grade 5 TEAE (Death) | 0 participants |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Assessment of Safety and Tolerability of ADI-PEG 20 | Grade 3 TEAE | 1 participants |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Assessment of Safety and Tolerability of ADI-PEG 20 | Any TEAE | 6 participants |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Assessment of Safety and Tolerability of ADI-PEG 20 | SAE | 4 participants |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Assessment of Safety and Tolerability of ADI-PEG 20 | Treatment-related TEAE | 5 participants |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Assessment of Safety and Tolerability of ADI-PEG 20 | Any TEAE | 6 participants |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Assessment of Safety and Tolerability of ADI-PEG 20 | Grade 3 TEAE | 2 participants |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Assessment of Safety and Tolerability of ADI-PEG 20 | Grade 4 TEAE | 1 participants |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Assessment of Safety and Tolerability of ADI-PEG 20 | Grade 5 TEAE (Death) | 0 participants |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Assessment of Safety and Tolerability of ADI-PEG 20 | SAE | 1 participants |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Assessment of Safety and Tolerability of ADI-PEG 20 | TEAE leading to withdrawal | 1 participants |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Assessment of Safety and Tolerability of ADI-PEG 20 | Treatment-related TEAE | 17 participants |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Assessment of Safety and Tolerability of ADI-PEG 20 | Grade 3 TEAE | 4 participants |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Assessment of Safety and Tolerability of ADI-PEG 20 | TEAE leading to withdrawal | 3 participants |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Assessment of Safety and Tolerability of ADI-PEG 20 | SAE | 6 participants |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Assessment of Safety and Tolerability of ADI-PEG 20 | Any TEAE | 19 participants |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Assessment of Safety and Tolerability of ADI-PEG 20 | Grade 5 TEAE (Death) | 1 participants |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Assessment of Safety and Tolerability of ADI-PEG 20 | Grade 4 TEAE | 1 participants |
Primary
Best Overall Clinical Tumor Response
Clinical tumor responses were evaluated using disease imaging (CT preferred) performed at baseline and at the end of every cycle. Responses were categorized according to RECIST. Per RECIST for target lesions and assessed by MRI: Complete Response (CR): Disappearance of all target lesions \[no evidence of disease\]; Partial Response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD): ≥ 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD): small changes that do not meet above criteria.
Time frame: Every 8 to 9 weeks for up to 12 months
Population: Includes all subjects who completed the study as planned or had tumor progression during the study
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Best Overall Clinical Tumor Response | Stable disease | 3 participants |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Best Overall Clinical Tumor Response | Complete/partial response | 0 participants |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Best Overall Clinical Tumor Response | Progressive disease | 3 participants |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Best Overall Clinical Tumor Response | Stable disease | 2 participants |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Best Overall Clinical Tumor Response | Complete/partial response | 0 participants |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Best Overall Clinical Tumor Response | Progressive disease | 4 participants |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Best Overall Clinical Tumor Response | Complete/partial response | 0 participants |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Best Overall Clinical Tumor Response | Progressive disease | 13 participants |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Best Overall Clinical Tumor Response | Stable disease | 4 participants |
Secondary
Correlation Between ASS Tumor Expression and Clinical Response
Expression of ASS was analyzed by immunohistochemistry in tumor samples (archived or biopsy) at baseline and compared with overall best clinical response per RECIST. ASS tumor expression is categorized as either negative or ≤ 5% positive tumor cells.
Time frame: Up to 12 months
Population: Includes all subjects who had an ASS antigen assay performed at Baseline
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Correlation Between ASS Tumor Expression and Clinical Response | ≤5% Positive ASS & Progressive Disease | 2 participants |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Correlation Between ASS Tumor Expression and Clinical Response | Negative ASS & Stable Disease | 1 participants |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Correlation Between ASS Tumor Expression and Clinical Response | Negative ASS & Progressive Disease | 3 participants |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Correlation Between ASS Tumor Expression and Clinical Response | Negative ASS & Missing Response | 0 participants |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Correlation Between ASS Tumor Expression and Clinical Response | Negative ASS & Missing Response | 0 participants |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Correlation Between ASS Tumor Expression and Clinical Response | ≤5% Positive ASS & Progressive Disease | 0 participants |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Correlation Between ASS Tumor Expression and Clinical Response | Negative ASS & Progressive Disease | 5 participants |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Correlation Between ASS Tumor Expression and Clinical Response | Negative ASS & Stable Disease | 1 participants |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Correlation Between ASS Tumor Expression and Clinical Response | Negative ASS & Missing Response | 2 participants |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Correlation Between ASS Tumor Expression and Clinical Response | Negative ASS & Stable Disease | 0 participants |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Correlation Between ASS Tumor Expression and Clinical Response | Negative ASS & Progressive Disease | 12 participants |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Correlation Between ASS Tumor Expression and Clinical Response | ≤5% Positive ASS & Progressive Disease | 3 participants |
Secondary
Metabolic Tumor Response
Metabolic tumor responses were evaluated using fluorodeoxyglucose (FDG) positron emission tomography (PET) at baseline, on day 4, and at the end of every cycle.
Time frame: Every 8 to 9 weeks for up to 12 months
Population: Includes all subjects who completed the study as planned or had tumor progression during the study
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Metabolic Tumor Response | Cycle 1 Day 50: Missing | 0 participants |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Metabolic Tumor Response | Cycle 1 Day 4: Partial metabolic response | 1 participants |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Metabolic Tumor Response | Cycle 1 Day 4: Missing | 0 participants |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Metabolic Tumor Response | Cycle 1 Day 50: Progressive metabolic disease | 2 participants |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Metabolic Tumor Response | Cycle 1 Day 4: Stable metabolic disease | 2 participants |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Metabolic Tumor Response | Cycle 1 Day 50: Partial metabolic response | 0 participants |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Metabolic Tumor Response | Cycle 1 Day 4: Progressive metabolic disease | 3 participants |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Metabolic Tumor Response | Cycle 1 Day 50: Stable metabolic disease | 4 participants |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Metabolic Tumor Response | Cycle 1 Day 4: Progressive metabolic disease | 2 participants |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Metabolic Tumor Response | Cycle 1 Day 4: Partial metabolic response | 0 participants |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Metabolic Tumor Response | Cycle 1 Day 50: Progressive metabolic disease | 1 participants |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Metabolic Tumor Response | Cycle 1 Day 50: Missing | 1 participants |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Metabolic Tumor Response | Cycle 1 Day 50: Partial metabolic response | 1 participants |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Metabolic Tumor Response | Cycle 1 Day 50: Stable metabolic disease | 3 participants |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Metabolic Tumor Response | Cycle 1 Day 4: Missing | 1 participants |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Metabolic Tumor Response | Cycle 1 Day 4: Stable metabolic disease | 3 participants |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Metabolic Tumor Response | Cycle 1 Day 50: Missing | 3 participants |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Metabolic Tumor Response | Cycle 1 Day 4: Partial metabolic response | 6 participants |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Metabolic Tumor Response | Cycle 1 Day 4: Stable metabolic disease | 6 participants |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Metabolic Tumor Response | Cycle 1 Day 4: Progressive metabolic disease | 4 participants |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Metabolic Tumor Response | Cycle 1 Day 4: Missing | 1 participants |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Metabolic Tumor Response | Cycle 1 Day 50: Partial metabolic response | 0 participants |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Metabolic Tumor Response | Cycle 1 Day 50: Stable metabolic disease | 5 participants |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Metabolic Tumor Response | Cycle 1 Day 50: Progressive metabolic disease | 9 participants |
Secondary
Summary of ADI-PEG 20 Immunogenicity Over Time
Blood samples were collected at baseline, day 1 (pre-injection), day 4, day 8, and every 7 days thereafter for detection of anti-ADI antibodies.
Time frame: Up to 12 months
Population: Includes all subjects who had at least 1 post-baseline blood sample with associated pharmacokinetic analysis. Means are presented for time points at which \>1 subject in any arm contributed data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 71 | 2.3 log 10 U/mL | Standard Deviation 0.6 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 36 | 0.8 log 10 U/mL | Standard Deviation 0.8 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 78 | 2.7 log 10 U/mL | Standard Deviation 0.6 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 64 | 2.0 log 10 U/mL | Standard Deviation 1 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 43 | 1.2 log 10 U/mL | Standard Deviation 1.2 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 106 | 3.0 log 10 U/mL | Standard Deviation 1 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 57 | 1.5 log 10 U/mL | Standard Deviation 0.8 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 50 | 1.5 log 10 U/mL | Standard Deviation 1.2 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 8 | 0.2 log 10 U/mL | Standard Deviation 0.4 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 120 | 3.0 log 10 U/mL | Standard Deviation 0 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 99 | 3.0 log 10 U/mL | Standard Deviation 1 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 15 | 0.5 log 10 U/mL | Standard Deviation 0.5 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 113 | 3.0 log 10 U/mL | Standard Deviation 0 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 92 | 3.0 log 10 U/mL | Standard Deviation 0 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 22 | 0.5 log 10 U/mL | Standard Deviation 0.5 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 4 | 0.2 log 10 U/mL | Standard Deviation 0.4 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 85 | 2.7 log 10 U/mL | Standard Deviation 0.6 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 29 | 0.8 log 10 U/mL | Standard Deviation 0.4 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 0 | 0.2 log 10 U/mL | Standard Deviation 0.4 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 36 | 1.8 log 10 U/mL | Standard Deviation 0.4 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 0 | 0.2 log 10 U/mL | Standard Deviation 0.5 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 4 | 0.0 log 10 U/mL | Standard Deviation 0 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 8 | 0.4 log 10 U/mL | Standard Deviation 0.5 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 15 | 0.6 log 10 U/mL | Standard Deviation 0.5 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 22 | 1.0 log 10 U/mL | Standard Deviation 0.6 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 29 | 1.4 log 10 U/mL | Standard Deviation 0.5 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 43 | 1.8 log 10 U/mL | Standard Deviation 0.4 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 50 | 2.2 log 10 U/mL | Standard Deviation 0.4 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 57 | 2.4 log 10 U/mL | Standard Deviation 0.5 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 64 | 2.0 log 10 U/mL | Standard Deviation 0 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 71 | 2.5 log 10 U/mL | Standard Deviation 0.7 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 78 | 2.5 log 10 U/mL | Standard Deviation 0.7 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 85 | 2.0 log 10 U/mL | Standard Deviation 0 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 92 | 3.0 log 10 U/mL | Standard Deviation 0 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 99 | 3.0 log 10 U/mL | — |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 106 | 3.0 log 10 U/mL | — |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 113 | 2.0 log 10 U/mL | — |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 120 | 4.0 log 10 U/mL | — |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 106 | 4.0 log 10 U/mL | Standard Deviation 0.8 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 78 | 4.0 log 10 U/mL | Standard Deviation 0.8 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 22 | 0.7 log 10 U/mL | Standard Deviation 0.5 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 0 | 0.1 log 10 U/mL | Standard Deviation 0.3 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 85 | 4.0 log 10 U/mL | Standard Deviation 0.8 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 15 | 0.8 log 10 U/mL | Standard Deviation 0.4 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 120 | 4.5 log 10 U/mL | Standard Deviation 1.3 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 92 | 4.0 log 10 U/mL | Standard Deviation 0.8 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 8 | 0.4 log 10 U/mL | Standard Deviation 0.5 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 50 | 2.9 log 10 U/mL | Standard Deviation 1.5 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 43 | 2.4 log 10 U/mL | Standard Deviation 1.2 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 113 | 4.0 log 10 U/mL | Standard Deviation 1.4 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 57 | 3.0 log 10 U/mL | Standard Deviation 1.2 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 36 | 1.9 log 10 U/mL | Standard Deviation 1.1 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 4 | 0.4 log 10 U/mL | Standard Deviation 0.5 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 64 | 3.0 log 10 U/mL | Standard Deviation 1.3 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 29 | 1.3 log 10 U/mL | Standard Deviation 0.9 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 99 | 3.8 log 10 U/mL | Standard Deviation 1.3 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of ADI-PEG 20 Immunogenicity Over Time | Day 71 | 3.5 log 10 U/mL | Standard Deviation 0.6 |
Secondary
Summary of ADI-PEG 20 Plasma Concentrations Over Time
Blood samples were collected on day 1 (pre-injection), day 4, day 8, and every 7 days thereafter for ADI-PEG 20 plasma concentrations.
Time frame: Up to 12 months
Population: Includes all subjects who had at least 1 post-baseline blood sample with associated pharmacokinetic analysis. Means are presented for time points at which \>1 subject in any arm contributed data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 4 | 35.5 nM | Standard Deviation 16 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 85 | 0.5 nM | Standard Deviation 0.7 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 43 | 12.0 nM | Standard Deviation 10.7 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 0 | 3.3 nM | Standard Deviation 2.9 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 78 | 2.8 nM | Standard Deviation 1.1 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 50 | 11.0 nM | Standard Deviation 14.9 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 15 | 37.7 nM | Standard Deviation 27.2 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 71 | 2.6 nM | Standard Deviation 1.3 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 57 | 8.4 nM | Standard Deviation 10.5 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 120 | 2.1 nM | Standard Deviation 0.7 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 64 | 8.0 nM | Standard Deviation 9.1 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 106 | 1.0 nM | Standard Deviation 1.7 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 22 | 24.1 nM | Standard Deviation 16.9 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 113 | 0.9 nM | Standard Deviation 0.1 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 99 | 0.9 nM | Standard Deviation 1.1 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 29 | 16.8 nM | Standard Deviation 11.1 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 8 | 33.2 nM | Standard Deviation 17.2 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 92 | 0.9 nM | Standard Deviation 0.8 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 36 | 11.2 nM | Standard Deviation 11.7 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 106 | 3.1 nM | — |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 0 | 4.4 nM | Standard Deviation 5.2 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 4 | 59.8 nM | Standard Deviation 35.7 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 8 | 46.3 nM | Standard Deviation 33.8 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 15 | 49.8 nM | Standard Deviation 59.4 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 22 | 61.2 nM | Standard Deviation 63.8 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 29 | 54.0 nM | Standard Deviation 58.2 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 36 | 50.0 nM | Standard Deviation 65.3 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 43 | 34.9 nM | Standard Deviation 47.2 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 50 | 19.0 nM | Standard Deviation 26.2 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 57 | 9.3 nM | Standard Deviation 10.3 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 64 | 14.7 nM | Standard Deviation 17.3 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 71 | 1.5 nM | Standard Deviation 0.7 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 78 | 0.6 nM | Standard Deviation 0.8 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 85 | 0.2 nM | Standard Deviation 0 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 92 | 0.6 nM | Standard Deviation 0.4 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 99 | 2.2 nM | — |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 113 | 2.0 nM | — |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 120 | 3.0 nM | — |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 78 | 2.6 nM | Standard Deviation 1.2 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 36 | 27.1 nM | Standard Deviation 42.3 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 120 | 4.0 nM | Standard Deviation 2.4 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 85 | 2.2 nM | Standard Deviation 1.9 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 29 | 40.9 nM | Standard Deviation 42.3 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 113 | 1.6 nM | Standard Deviation 1.8 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 92 | 2.6 nM | Standard Deviation 2.9 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 22 | 47.5 nM | Standard Deviation 40.2 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 0 | 1.9 nM | Standard Deviation 1.7 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 99 | 2.4 nM | Standard Deviation 1.7 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 15 | 54.0 nM | Standard Deviation 36.4 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 57 | 10.0 nM | Standard Deviation 15.6 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 8 | 60.9 nM | Standard Deviation 35.5 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 64 | 10.0 nM | Standard Deviation 16.2 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 50 | 13.2 nM | Standard Deviation 25.7 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 106 | 0.9 nM | Standard Deviation 0.8 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 71 | 3.8 nM | Standard Deviation 2.9 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 43 | 11.9 nM | Standard Deviation 20.2 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of ADI-PEG 20 Plasma Concentrations Over Time | Day 4 | 57.2 nM | Standard Deviation 39.9 |
Secondary
Summary of Plasma Arginine Levels Over Time
Blood samples were collected at baseline, day 1 (pre-injection), day 4, day 8, and every 7 days thereafter for plasma arginine levels.
Time frame: Up to 9 months
Population: Includes all subjects who had at least 1 post-baseline blood sample with associated pharmacokinetic analysis. Means are presented for time points at which \>1 subject in any arm contributed data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 4 | 2 uM | Standard Deviation 0 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 78 | 78 uM | Standard Deviation 39 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 43 | 23 uM | Standard Deviation 34 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 106 | 52 uM | Standard Deviation 34 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 71 | 68 uM | Standard Deviation 33 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 50 | 58 uM | Standard Deviation 46 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 0 | 55 uM | Standard Deviation 17 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 64 | 30 uM | Standard Deviation 29 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 57 | 38 uM | Standard Deviation 30 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 15 | 4 uM | Standard Deviation 6 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 120 | 64 uM | Standard Deviation 34 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 99 | 67 uM | Standard Deviation 11 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 22 | 9 uM | Standard Deviation 11 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 113 | 59 uM | Standard Deviation 15 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 92 | 98 uM | Standard Deviation 42 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 29 | 14 uM | Standard Deviation 24 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 8 | 2 uM | Standard Deviation 0 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 85 | 75 uM | Standard Deviation 38 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 36 | 20 uM | Standard Deviation 28 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 106 | 43 uM | — |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 4 | 9 uM | Standard Deviation 20 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 8 | 12 uM | Standard Deviation 18 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 15 | 29 uM | Standard Deviation 22 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 22 | 22 uM | Standard Deviation 23 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 29 | 19 uM | Standard Deviation 24 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 36 | 29 uM | Standard Deviation 26 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 43 | 35 uM | Standard Deviation 31 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 50 | 24 uM | Standard Deviation 21 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 57 | 27 uM | Standard Deviation 22 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 64 | 30 uM | Standard Deviation 26 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 71 | 63 uM | Standard Deviation 13 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 78 | 105 uM | Standard Deviation 2 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 85 | 64 uM | Standard Deviation 28 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 92 | 95 uM | Standard Deviation 6 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 99 | 89 uM | — |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 0 | 62 uM | Standard Deviation 22 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 113 | 53 uM | — |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 120 | 59 uM | — |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 78 | 60 uM | Standard Deviation 26 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 29 | 23 uM | Standard Deviation 32 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 4 | 4 uM | Standard Deviation 11 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 85 | 74 uM | Standard Deviation 24 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 22 | 21 uM | Standard Deviation 33 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 120 | 60 uM | Standard Deviation 16 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 92 | 71 uM | Standard Deviation 23 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 15 | 7 uM | Standard Deviation 16 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 113 | 59 uM | Standard Deviation 7 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 99 | 52 uM | Standard Deviation 16 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 57 | 40 uM | Standard Deviation 31 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 50 | 44 uM | Standard Deviation 37 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 8 | 3 uM | Standard Deviation 7 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 64 | 42 uM | Standard Deviation 35 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 43 | 48 uM | Standard Deviation 44 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 0 | 49 uM | Standard Deviation 11 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 71 | 50 uM | Standard Deviation 34 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 36 | 31 uM | Standard Deviation 34 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of Plasma Arginine Levels Over Time | Day 106 | 77 uM | Standard Deviation 28 |
Secondary
Summary of Plasma Citrulline Levels Over Time
Blood samples were collected at baseline, day 1 (pre-injection), day 4, day 8, and every 7 days thereafter for plasma citrulline levels.
Time frame: Up to 9 months
Population: Includes all subjects who had at least 1 post-baseline blood sample with associated pharmacokinetic analysis. Means are presented for time points at which \>1 subject in any arm contributed data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 4 | 195 uM | Standard Deviation 89 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 85 | 50 uM | Standard Deviation 30 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 43 | 106 uM | Standard Deviation 81 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 0 | 38 uM | Standard Deviation 17 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 78 | 40 uM | Standard Deviation 12 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 50 | 58 uM | Standard Deviation 31 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 15 | 127 uM | Standard Deviation 71 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 71 | 35 uM | Standard Deviation 9 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 57 | 71 uM | Standard Deviation 51 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 120 | 37 uM | Standard Deviation 14 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 64 | 76 uM | Standard Deviation 80 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 106 | 33 uM | Standard Deviation 21 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 22 | 141 uM | Standard Deviation 102 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 113 | 35 uM | Standard Deviation 12 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 99 | 33 uM | Standard Deviation 13 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 29 | 99 uM | Standard Deviation 59 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 8 | 152 uM | Standard Deviation 40 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 92 | 44 uM | Standard Deviation 21 |
| Cohort 1: ADI-PEG 20 40 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 36 | 116 uM | Standard Deviation 75 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 106 | 33 uM | — |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 0 | 29 uM | Standard Deviation 8 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 4 | 158 uM | Standard Deviation 84 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 8 | 121 uM | Standard Deviation 51 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 15 | 125 uM | Standard Deviation 122 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 22 | 174 uM | Standard Deviation 165 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 29 | 126 uM | Standard Deviation 126 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 36 | 104 uM | Standard Deviation 115 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 43 | 135 uM | Standard Deviation 149 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 50 | 77 uM | Standard Deviation 88 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 57 | 47 uM | Standard Deviation 29 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 64 | 108 uM | Standard Deviation 133 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 71 | 19 uM | Standard Deviation 9 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 78 | 44 uM | Standard Deviation 29 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 85 | 23 uM | Standard Deviation 6 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 92 | 27 uM | Standard Deviation 2 |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 99 | 31 uM | — |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 113 | 22 uM | — |
| Cohort 2: ADI-PEG 20 80 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 120 | 47 uM | — |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 78 | 30 uM | Standard Deviation 19 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 36 | 139 uM | Standard Deviation 149 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 120 | 22 uM | Standard Deviation 8 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 85 | 32 uM | Standard Deviation 11 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 29 | 169 uM | Standard Deviation 148 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 113 | 23 uM | Standard Deviation 10 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 92 | 29 uM | Standard Deviation 18 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 22 | 245 uM | Standard Deviation 175 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 0 | 23 uM | Standard Deviation 14 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 99 | 23 uM | Standard Deviation 12 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 15 | 280 uM | Standard Deviation 150 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 57 | 64 uM | Standard Deviation 76 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 8 | 280 uM | Standard Deviation 125 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 64 | 60 uM | Standard Deviation 54 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 50 | 66 uM | Standard Deviation 76 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 106 | 29 uM | Standard Deviation 10 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 71 | 45 uM | Standard Deviation 34 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 43 | 71 uM | Standard Deviation 72 |
| Cohort 3: ADI-PEG 20 160 IU/m^2/Week | Summary of Plasma Citrulline Levels Over Time | Day 4 | 225 uM | Standard Deviation 106 |