Relapsed or Refractory Multiple Myeloma
Conditions
Keywords
absolute lymphocyte count, antitumor, cancer, immunotherapy, immunochemotherapy, interleukin-15, multiple myeloma, NK cell, refractory, relapsed, T cell, white blood cell count
Brief summary
This is a Phase I/II, open-label, multi-center, competitive enrollment and dose escalation study of N-803 in patients with relapsed or refractory multiple myeloma.
Detailed description
The purpose of this study is to evaluate the safety, determine the Maximum Tolerated Dose (MTD) or the Minimum Efficacious Dose (MED) and characterize the immunogenicity and pharmacokinetic profile of N-803 in treated patients. The effect of N-803 on the peripheral absolute lymphocyte counts and white blood cell counts, the number and phenotype of peripheral blood T (total and subsets) and NK cells will be evaluated. The anti-tumor responses of N-803 will also be assessed in this trial.
Interventions
BIOLOGICALN-803
Intravenous infusion for cohort 1, 2, 3 and 4; subcutaneous injection for cohort 5, 6 and 7; two 6-week treatment cycles: ALT-803 on Day 1, 8, 15, 22; stable or benefitting patients may receive up to two additional 6-week cycles
Sponsors
National Cancer Institute (NCI)
Altor BioScience
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
ENTRY CRITERIA: DISEASE CHARACTERISTICS: * Confirmed diagnosis of relapsed/refractory multiple myeloma after treatment with at least two different previous regimens. * Refractory disease is defined as progressive disease while on therapy or progression within 60 days of therapy. * Progressive disease is defined by a 25% increase from the lowest response value in specified tests. * Measurable disease as defined by at least one of the following: * Serum M-protein ≥ 1g/dL (for IgG, IgM) or 0.5 g/dL (for IgA) * Urine M-protein ≥ 200mg/24hours * Serum free light chains ≥ 10 mg/dL and abnormal kappa/lambda ratio PRIOR/CONCURRENT THERAPY: * No anti-myeloma treatments within 14 days before the start of study treatment. * Must have recovered from side effects of prior treatments. PATIENT CHARACTERISTICS: Performance Status • ECOG 0, 1, or 2 Bone Marrow Reserve * Absolute neutrophil count (AGC/ANC) ≥ 1000/uL * Platelets ≥ 30,000/uL * Hemoglobin ≥ 8g/dL * Absolute lymphocytes ≥ 800/uL * Leukocytes ≥ 3,000/uL Renal Function • Glomerular Filtration Rate (GFR) \> 40mL/min or Serum creatinine ≤ 1.5 X ULN Hepatic Function * Total bilirubin ≤ 2.0 X ULN * AST, ALT, ALP ≤ 3.0 X ULN, or ≤ 5.0 X ULN (if liver metastases exist) * No positive Hep C serology or active Hep B infection Cardiovascular * No congestive heart failure \< 6 months * No unstable angina pectoris \< 6 months * No myocardial infarction \< 6 months * No history of ventricular arrhythmias * No history of supraventricular arrhythmias * No NYHA Class \> II CHF * No marked baseline prolongation of QT/QTc interval Pulmonary • Normal clinical assessment of pulmonary function Other * Negative serum pregnancy test if female and of childbearing potential * Women who are not pregnant or nursing * Subjects, both females and males, with reproductive potential must agree to use effective contraceptive measures for the duration of the study * No known autoimmune disease other than corrected hypothyroidism * No known prior organ allograft or allogeneic transplantation * Not HIV positive * No history or evidence of uncontrollable CNS disease * No psychiatric illness/social situation * No other illness that in the opinion of the investigator would exclude the subject from participating in the study * Must provide informed consent and HIPPA authorization and agree to comply with all protocol-specified procedures and follow-up evaluations * No active systemic infection requiring parenteral antibiotic therapy * No on-going chronic systemic corticosteroid (\>10 mg daily prednisone equivalent) use or other immunosuppressive therapy (a history of mild asthma not requiring therapy is eligible). Inhaled or topical steroids, and adrenal replacement steroid doses ≤ 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events | 24 weeks | For phase I - Number of Participants with Treatment Emergent Adverse Events that occur or worsen after the first dose of study treatment. |
| Disease Response Rate of Treated Patients | Starts at Week 11 - 12 and Week 23 - 24 | CR- negative SIFE and UIFE, disappearance of any soft tissue plasmacytomas, and \< or = to 5% plasma cells in bone marrow VGPR - either + SIFE and UIFE and - SPEP and UPEP or reduction in serum M-protein \> or = to 90% and urine m-protein level \<100mg per 24h PR - if measurable serum an urine m-protein them reduction of serum m-protein by \>=50% and reduction in 24h urinary m protein by \>=90% or to \<200mg per 24h if unmeasurable serum and urine m-protein then \>= 50% decrease in the difference between involve and uninvolved FLC levels If unmeasurable serum and urine m-protein and serum FLC assay then \>= 50% reduction in plasma cells, provide baseline bone marrow plasma cell percentage was \>=30% In addition to the above listed criteria, if present at baseline, a \>=50% reduction in the size of soft tissue plasmacytomas is also required PD - defined via International Myeloma Working Group uniform response criteria: disease progression SD - not meeting criteria for CR, VGPR, PR or PD |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Characterization of the Pharmacokinetic Profile - Maximum Observed Concentration (Cmax) | PK timepoint up to 72 hours +/- 6 hours | maximum observed concentration (Cmax) |
| Characterization of the Pharmacokinetic Profile - Area Under the Plasma Concentration Curve | Samples were collected and the AUC was determined at 24 hours and at time t (last measurable concentration). The AUC was calculated for 168 hours and time to infinity. | Area under the plasma concentration curve from time 0 through the last measurable concentration (AUC0-t). PK samples were obtained from the start of treatment until 72 hours. The AUC0-168 and AUC0-inf were calculated with noncompartmental pharmacokinetic analysis equations. |
| Characterization of the Pharmacokinetic Profile - Clearance (CL) | PK timepoint up to 72 hours +/- 6 hours | Clearance (CL) |
| Characterization of the Pharmacokinetic Profile - Half-life (t½) | PK timepoint up to 72 hours +/- 6 hours | Half-life (t½) - The period of time required for the concentration or amount of drug in the body to be reduced by one-half. |
| Immunogenicity - Anti-drug Antibody (ADA) | From Baseline up to Week 12 | Number of patients with a positive Anti-drug Antibody (ADA) result |
| Characterization of the Pharmacokinetic Profile - Apparent (Extravascular) Clearance (CL/F) | PK timepoint up to 72 hours +/- 6 hours | Apparent (Extravascular) Clearance (CL/F) |
| Characterization of the Pharmacokinetic Profile - Apparent (Extravascular) Volume of Distribution (Vz/F) | PK timepoint up to 72 hours +/- 6 hours | Apparent volume of distribution is a ratio of the total amount of drug in the body to the plasma concentration of the drugs such that Vd = amount of drug in body/plasma drug concentration |
| Characterization of the Pharmacokinetic Profile - Vss Volume of Distribution at Steady State | PK timepoint up to 72 hours +/- 6 hours | Vss Volume of distribution at steady state is a ratio of the total amount of drug in the body to the plasma concentration of the drugs such that Vd = amount of drug in body/plasma drug concentration |
| Characterization of the Pharmacokinetic Profile - Time of the Observed Maximum Concentration (Tmax) | PK timepoint up to 72 hours +/- 6 hours | time of the observed maximum concentration (Tmax) |
Countries
United States
Participant flow
Pre-assignment details
Only the Phase 1b portion of the study enrolled participants. The study was terminated early, so no participants were enrolled on the Phase 2 portion of the study
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: ALT-803 - IV 1 ug/kg ALT-803: Intravenous infusion for cohort 1, 2, 3 and 4; two 6-week treatment cycles: ALT-803 on Day 1, 8, 15, 22; stable or benefitting patients may receive up to two additional 6-week cycles | 3 |
| Cohort 2: ALT-803 - IV 3 ug/kg ALT-803: Intravenous infusion for cohort 1, 2, 3 and 4; two 6-week treatment cycles: ALT-803 on Day 1, 8, 15, 22; stable or benefitting patients may receive up to two additional 6-week cycles | 3 |
| Cohort 3: ALT-803 - IV 6 ug/kg ALT-803: Intravenous infusion for cohort 1, 2, 3 and 4; two 6-week treatment cycles: ALT-803 on Day 1, 8, 15, 22; stable or benefitting patients may receive up to two additional 6-week cycles | 3 |
| Cohort 4: ALT-803 - IV 10 ug/kg ALT-803: Intravenous infusion for cohort 1, 2, 3 and 4; two 6-week treatment cycles: ALT-803 on Day 1, 8, 15, 22; stable or benefitting patients may receive up to two additional 6-week cycles | 3 |
| Cohort 5: ALT-803 - SQ 10 ug/kg ALT-803: subcutaneous injection for cohort 5, 6 and 7; two 6-week treatment cycles: ALT-803 on Day 1, 8, 15, 22; stable or benefitting patients may receive up to two additional 6-week cycles | 4 |
| Cohort 6: ALT-803 - SQ 15 ug/kg ALT-803: subcutaneous injection for cohort 5, 6 and 7; two 6-week treatment cycles: ALT-803 on Day 1, 8, 15, 22; stable or benefitting patients may receive up to two additional 6-week cycles | 3 |
| Cohort 7: ALT-803 - SQ 20 ug/kg ALT-803: subcutaneous injection for cohort 5, 6 and 7; two 6-week treatment cycles: ALT-803 on Day 1, 8, 15, 22; stable or benefitting patients may receive up to two additional 6-week cycles | 0 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 1 | 0 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Progressive Disease | 3 | 2 | 2 | 1 | 4 | 2 | 0 |
Baseline characteristics
| Characteristic | Cohort 1: ALT-803 - IV 1 ug/kg | Total | Cohort 6: ALT-803 - SQ 15 ug/kg | Cohort 5: ALT-803 - SQ 10 ug/kg | Cohort 4: ALT-803 - IV 10 ug/kg | Cohort 3: ALT-803 - IV 6 ug/kg | Cohort 2: ALT-803 - IV 3 ug/kg | Cohort 7: ALT-803 - SQ 20 ug/kg |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 71.7 years STANDARD_DEVIATION 4.16 | 61.5 years STANDARD_DEVIATION 13.05 | 67.0 years STANDARD_DEVIATION 5 | 49.8 years STANDARD_DEVIATION 22.63 | 61.7 years STANDARD_DEVIATION 12.1 | 63.7 years STANDARD_DEVIATION 6.35 | 59.3 years STANDARD_DEVIATION 6.66 | — |
| Patients with Relapsed or Refractory Multiple Myeloma | 3 Participants | 19 Participants | 3 Participants | 4 Participants | 3 Participants | 3 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 17 Participants | 3 Participants | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 0 Participants |
| Sex: Female, Male Female | 2 Participants | 9 Participants | 2 Participants | 0 Participants | 2 Participants | 3 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 10 Participants | 1 Participants | 4 Participants | 1 Participants | 0 Participants | 3 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 3 | 0 / 3 | 1 / 3 | 0 / 3 | 3 / 4 | 0 / 3 | 0 / 0 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 4 / 4 | 3 / 3 | 0 / 0 |
| serious Total, serious adverse events | 2 / 3 | 1 / 3 | 1 / 3 | 0 / 3 | 3 / 4 | 0 / 3 | 0 / 0 |
Outcome results
Primary
Disease Response Rate of Treated Patients
CR- negative SIFE and UIFE, disappearance of any soft tissue plasmacytomas, and \< or = to 5% plasma cells in bone marrow VGPR - either + SIFE and UIFE and - SPEP and UPEP or reduction in serum M-protein \> or = to 90% and urine m-protein level \<100mg per 24h PR - if measurable serum an urine m-protein them reduction of serum m-protein by \>=50% and reduction in 24h urinary m protein by \>=90% or to \<200mg per 24h if unmeasurable serum and urine m-protein then \>= 50% decrease in the difference between involve and uninvolved FLC levels If unmeasurable serum and urine m-protein and serum FLC assay then \>= 50% reduction in plasma cells, provide baseline bone marrow plasma cell percentage was \>=30% In addition to the above listed criteria, if present at baseline, a \>=50% reduction in the size of soft tissue plasmacytomas is also required PD - defined via International Myeloma Working Group uniform response criteria: disease progression SD - not meeting criteria for CR, VGPR, PR or PD
Time frame: Starts at Week 11 - 12 and Week 23 - 24
Population: Cohort 5: N-803 - SQ 10 ug/kg - one subject only received 2 doses of study drug. This subject is not evaluable for tumor response assessment.~Cohort 7: N-803 - SQ 20 ug/kg did not enroll any subjects
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: N-803 - IV 1 ug/kg | Disease Response Rate of Treated Patients | Progressive Disease | 3 Participants |
| Cohort 1: N-803 - IV 1 ug/kg | Disease Response Rate of Treated Patients | Stable Disease | 0 Participants |
| Cohort 1: N-803 - IV 1 ug/kg | Disease Response Rate of Treated Patients | Not available to evaluate | 0 Participants |
| Cohort 2: N-803 - IV 3 ug/kg | Disease Response Rate of Treated Patients | Progressive Disease | 2 Participants |
| Cohort 2: N-803 - IV 3 ug/kg | Disease Response Rate of Treated Patients | Stable Disease | 1 Participants |
| Cohort 2: N-803 - IV 3 ug/kg | Disease Response Rate of Treated Patients | Not available to evaluate | 0 Participants |
| Cohort 3: N-803 - IV 6 ug/kg | Disease Response Rate of Treated Patients | Progressive Disease | 1 Participants |
| Cohort 3: N-803 - IV 6 ug/kg | Disease Response Rate of Treated Patients | Stable Disease | 1 Participants |
| Cohort 3: N-803 - IV 6 ug/kg | Disease Response Rate of Treated Patients | Not available to evaluate | 1 Participants |
| Cohort 4: N-803 - IV 10 ug/kg | Disease Response Rate of Treated Patients | Progressive Disease | 2 Participants |
| Cohort 4: N-803 - IV 10 ug/kg | Disease Response Rate of Treated Patients | Stable Disease | 1 Participants |
| Cohort 4: N-803 - IV 10 ug/kg | Disease Response Rate of Treated Patients | Not available to evaluate | 0 Participants |
| Cohort 5: N-803 - SQ 10 ug/kg | Disease Response Rate of Treated Patients | Progressive Disease | 2 Participants |
| Cohort 5: N-803 - SQ 10 ug/kg | Disease Response Rate of Treated Patients | Stable Disease | 0 Participants |
| Cohort 5: N-803 - SQ 10 ug/kg | Disease Response Rate of Treated Patients | Not available to evaluate | 1 Participants |
| Cohort 6: N-803 - SQ 15 ug/kg | Disease Response Rate of Treated Patients | Stable Disease | 1 Participants |
| Cohort 6: N-803 - SQ 15 ug/kg | Disease Response Rate of Treated Patients | Not available to evaluate | 0 Participants |
| Cohort 6: N-803 - SQ 15 ug/kg | Disease Response Rate of Treated Patients | Progressive Disease | 2 Participants |
Primary
Number of Participants With Treatment Emergent Adverse Events
For phase I - Number of Participants with Treatment Emergent Adverse Events that occur or worsen after the first dose of study treatment.
Time frame: 24 weeks
Population: Cohort 7: N-803 - SQ 20 ug/kg did not enroll any subjects
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: N-803 - IV 1 ug/kg | Number of Participants With Treatment Emergent Adverse Events | 3 Participants |
| Cohort 2: N-803 - IV 3 ug/kg | Number of Participants With Treatment Emergent Adverse Events | 3 Participants |
| Cohort 3: N-803 - IV 6 ug/kg | Number of Participants With Treatment Emergent Adverse Events | 3 Participants |
| Cohort 4: N-803 - IV 10 ug/kg | Number of Participants With Treatment Emergent Adverse Events | 3 Participants |
| Cohort 5: N-803 - SQ 10 ug/kg | Number of Participants With Treatment Emergent Adverse Events | 4 Participants |
| Cohort 6: N-803 - SQ 15 ug/kg | Number of Participants With Treatment Emergent Adverse Events | 3 Participants |
Secondary
Characterization of the Pharmacokinetic Profile - Apparent (Extravascular) Clearance (CL/F)
Apparent (Extravascular) Clearance (CL/F)
Time frame: PK timepoint up to 72 hours +/- 6 hours
Population: In addition, 6 out of 7 SC patients (Cohorts 5 and 6) had insufficient measurable post-tmax sampling to allow for evaluation of the terminal phase-dependent PK parameters (ie, t½, CL/F, Vz/F, AUC0-168, AUC0-∞).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cohort 2: N-803 - IV 3 ug/kg | Characterization of the Pharmacokinetic Profile - Apparent (Extravascular) Clearance (CL/F) | 462 mL/hr/kg |
Secondary
Characterization of the Pharmacokinetic Profile - Apparent (Extravascular) Volume of Distribution (Vz/F)
Apparent volume of distribution is a ratio of the total amount of drug in the body to the plasma concentration of the drugs such that Vd = amount of drug in body/plasma drug concentration
Time frame: PK timepoint up to 72 hours +/- 6 hours
Population: Cohort 7: N-803 - SQ 20 ug/kg did not enroll any subjects In addition, 6 out of 7 SC patients (Cohorts 5 and 6) had insufficient measurable post-tmax sampling to allow for evaluation of the terminal phase-dependent PK parameters (ie, t½, CL/F, Vz/F, AUC0-168, AUC0-∞).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cohort 2: N-803 - IV 3 ug/kg | Characterization of the Pharmacokinetic Profile - Apparent (Extravascular) Volume of Distribution (Vz/F) | 23500 mL/kg |
Secondary
Characterization of the Pharmacokinetic Profile - Area Under the Plasma Concentration Curve
Area under the plasma concentration curve from time 0 through the last measurable concentration (AUC0-t). PK samples were obtained from the start of treatment until 72 hours. The AUC0-168 and AUC0-inf were calculated with noncompartmental pharmacokinetic analysis equations.
Time frame: Samples were collected and the AUC was determined at 24 hours and at time t (last measurable concentration). The AUC was calculated for 168 hours and time to infinity.
Population: Cohort 7: N-803 - SQ 20 ug/kg did not enroll any subjects In addition, 6 out of 7 SC patients (Cohorts 5 and 6) had insufficient measurable post-tmax sampling to allow for evaluation of the terminal phase-dependent PK parameters (ie, t½, CL/F, Vz/F, AUC0-168, AUC0-∞).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Cohort 1: N-803 - IV 1 ug/kg | Characterization of the Pharmacokinetic Profile - Area Under the Plasma Concentration Curve | AUC0-24 | 10.6 hr x ng/mL |
| Cohort 1: N-803 - IV 1 ug/kg | Characterization of the Pharmacokinetic Profile - Area Under the Plasma Concentration Curve | AUC0-inf | 10.6 hr x ng/mL |
| Cohort 1: N-803 - IV 1 ug/kg | Characterization of the Pharmacokinetic Profile - Area Under the Plasma Concentration Curve | AUC0-168 | 10.6 hr x ng/mL |
| Cohort 1: N-803 - IV 1 ug/kg | Characterization of the Pharmacokinetic Profile - Area Under the Plasma Concentration Curve | AUC0-t | 10.5 hr x ng/mL |
| Cohort 2: N-803 - IV 3 ug/kg | Characterization of the Pharmacokinetic Profile - Area Under the Plasma Concentration Curve | AUC0-inf | 141 hr x ng/mL |
| Cohort 2: N-803 - IV 3 ug/kg | Characterization of the Pharmacokinetic Profile - Area Under the Plasma Concentration Curve | AUC0-t | 129 hr x ng/mL |
| Cohort 2: N-803 - IV 3 ug/kg | Characterization of the Pharmacokinetic Profile - Area Under the Plasma Concentration Curve | AUC0-24 | 141 hr x ng/mL |
| Cohort 2: N-803 - IV 3 ug/kg | Characterization of the Pharmacokinetic Profile - Area Under the Plasma Concentration Curve | AUC0-168 | 141 hr x ng/mL |
| Cohort 3: N-803 - IV 6 ug/kg | Characterization of the Pharmacokinetic Profile - Area Under the Plasma Concentration Curve | AUC0-24 | 731 hr x ng/mL |
| Cohort 3: N-803 - IV 6 ug/kg | Characterization of the Pharmacokinetic Profile - Area Under the Plasma Concentration Curve | AUC0-t | 634 hr x ng/mL |
| Cohort 3: N-803 - IV 6 ug/kg | Characterization of the Pharmacokinetic Profile - Area Under the Plasma Concentration Curve | AUC0-inf | 732 hr x ng/mL |
| Cohort 3: N-803 - IV 6 ug/kg | Characterization of the Pharmacokinetic Profile - Area Under the Plasma Concentration Curve | AUC0-168 | 732 hr x ng/mL |
| Cohort 4: N-803 - IV 10 ug/kg | Characterization of the Pharmacokinetic Profile - Area Under the Plasma Concentration Curve | AUC0-inf | 814 hr x ng/mL |
| Cohort 4: N-803 - IV 10 ug/kg | Characterization of the Pharmacokinetic Profile - Area Under the Plasma Concentration Curve | AUC0-t | 808 hr x ng/mL |
| Cohort 4: N-803 - IV 10 ug/kg | Characterization of the Pharmacokinetic Profile - Area Under the Plasma Concentration Curve | AUC0-24 | 811 hr x ng/mL |
| Cohort 4: N-803 - IV 10 ug/kg | Characterization of the Pharmacokinetic Profile - Area Under the Plasma Concentration Curve | AUC0-168 | 813 hr x ng/mL |
| Cohort 5: N-803 - SQ 10 ug/kg | Characterization of the Pharmacokinetic Profile - Area Under the Plasma Concentration Curve | AUC0-t | 13.6 hr x ng/mL |
| Cohort 5: N-803 - SQ 10 ug/kg | Characterization of the Pharmacokinetic Profile - Area Under the Plasma Concentration Curve | AUC0-24 | 5.01 hr x ng/mL |
| Cohort 6: N-803 - SQ 15 ug/kg | Characterization of the Pharmacokinetic Profile - Area Under the Plasma Concentration Curve | AUC0-inf | 32.5 hr x ng/mL |
| Cohort 6: N-803 - SQ 15 ug/kg | Characterization of the Pharmacokinetic Profile - Area Under the Plasma Concentration Curve | AUC0-t | 60.4 hr x ng/mL |
| Cohort 6: N-803 - SQ 15 ug/kg | Characterization of the Pharmacokinetic Profile - Area Under the Plasma Concentration Curve | AUC0-24 | 31.1 hr x ng/mL |
| Cohort 6: N-803 - SQ 15 ug/kg | Characterization of the Pharmacokinetic Profile - Area Under the Plasma Concentration Curve | AUC0-168 | 31.4 hr x ng/mL |
Secondary
Characterization of the Pharmacokinetic Profile - Clearance (CL)
Clearance (CL)
Time frame: PK timepoint up to 72 hours +/- 6 hours
Population: Cohort 7: N-803 - SQ 20 ug/kg did not enroll any subjects~Cohorts 1-4 - Clearance (CL)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cohort 1: N-803 - IV 1 ug/kg | Characterization of the Pharmacokinetic Profile - Clearance (CL) | 99.9 mL/hr/kg |
| Cohort 2: N-803 - IV 3 ug/kg | Characterization of the Pharmacokinetic Profile - Clearance (CL) | 22.0 mL/hr/kg |
| Cohort 3: N-803 - IV 6 ug/kg | Characterization of the Pharmacokinetic Profile - Clearance (CL) | 8.4 mL/hr/kg |
| Cohort 4: N-803 - IV 10 ug/kg | Characterization of the Pharmacokinetic Profile - Clearance (CL) | 13.7 mL/hr/kg |
Secondary
Characterization of the Pharmacokinetic Profile - Half-life (t½)
Half-life (t½) - The period of time required for the concentration or amount of drug in the body to be reduced by one-half.
Time frame: PK timepoint up to 72 hours +/- 6 hours
Population: Cohort 7: N-803 - SQ 20 ug/kg did not enroll any subjects. In addition, 6 out of 7 SC patients (Cohorts 5 and 6) had insufficient measurable post-tmax sampling to allow for evaluation of the terminal phase-dependent PK parameters (ie, t½, CL/F, Vz/F, AUC0-168, AUC0-∞).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cohort 1: N-803 - IV 1 ug/kg | Characterization of the Pharmacokinetic Profile - Half-life (t½) | 0.773 Hours |
| Cohort 2: N-803 - IV 3 ug/kg | Characterization of the Pharmacokinetic Profile - Half-life (t½) | 2.41 Hours |
| Cohort 3: N-803 - IV 6 ug/kg | Characterization of the Pharmacokinetic Profile - Half-life (t½) | 2.21 Hours |
| Cohort 4: N-803 - IV 10 ug/kg | Characterization of the Pharmacokinetic Profile - Half-life (t½) | 3.07 Hours |
| Cohort 6: N-803 - SQ 15 ug/kg | Characterization of the Pharmacokinetic Profile - Half-life (t½) | 35.3 Hours |
Secondary
Characterization of the Pharmacokinetic Profile - Maximum Observed Concentration (Cmax)
maximum observed concentration (Cmax)
Time frame: PK timepoint up to 72 hours +/- 6 hours
Population: Cohort 7: N-803 - SQ 20 ug/kg did not enroll any subjects
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: N-803 - IV 1 ug/kg | Characterization of the Pharmacokinetic Profile - Maximum Observed Concentration (Cmax) | 8.45 ng/mL | Standard Deviation 1.78 |
| Cohort 2: N-803 - IV 3 ug/kg | Characterization of the Pharmacokinetic Profile - Maximum Observed Concentration (Cmax) | 42.7 ng/mL | Standard Deviation 1.76 |
| Cohort 3: N-803 - IV 6 ug/kg | Characterization of the Pharmacokinetic Profile - Maximum Observed Concentration (Cmax) | 142 ng/mL | Standard Deviation 26.6 |
| Cohort 4: N-803 - IV 10 ug/kg | Characterization of the Pharmacokinetic Profile - Maximum Observed Concentration (Cmax) | 144 ng/mL | Standard Deviation 70.7 |
| Cohort 5: N-803 - SQ 10 ug/kg | Characterization of the Pharmacokinetic Profile - Maximum Observed Concentration (Cmax) | 0.383 ng/mL | Standard Deviation 0.111 |
| Cohort 6: N-803 - SQ 15 ug/kg | Characterization of the Pharmacokinetic Profile - Maximum Observed Concentration (Cmax) | 1.69 ng/mL | Standard Deviation 1.41 |
Secondary
Characterization of the Pharmacokinetic Profile - Time of the Observed Maximum Concentration (Tmax)
time of the observed maximum concentration (Tmax)
Time frame: PK timepoint up to 72 hours +/- 6 hours
Population: Cohort 7: N-803 - SQ 20 ug/kg did not enroll any subjects
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: N-803 - IV 1 ug/kg | Characterization of the Pharmacokinetic Profile - Time of the Observed Maximum Concentration (Tmax) | 0.583 Hours |
| Cohort 2: N-803 - IV 3 ug/kg | Characterization of the Pharmacokinetic Profile - Time of the Observed Maximum Concentration (Tmax) | 0.583 Hours |
| Cohort 3: N-803 - IV 6 ug/kg | Characterization of the Pharmacokinetic Profile - Time of the Observed Maximum Concentration (Tmax) | 0.65 Hours |
| Cohort 4: N-803 - IV 10 ug/kg | Characterization of the Pharmacokinetic Profile - Time of the Observed Maximum Concentration (Tmax) | 0.667 Hours |
| Cohort 5: N-803 - SQ 10 ug/kg | Characterization of the Pharmacokinetic Profile - Time of the Observed Maximum Concentration (Tmax) | 33.1 Hours |
| Cohort 6: N-803 - SQ 15 ug/kg | Characterization of the Pharmacokinetic Profile - Time of the Observed Maximum Concentration (Tmax) | 6.0 Hours |
Secondary
Characterization of the Pharmacokinetic Profile - Vss Volume of Distribution at Steady State
Vss Volume of distribution at steady state is a ratio of the total amount of drug in the body to the plasma concentration of the drugs such that Vd = amount of drug in body/plasma drug concentration
Time frame: PK timepoint up to 72 hours +/- 6 hours
Population: Cohort 7: N-803 - SQ 20 ug/kg did not enroll any subjects
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cohort 1: N-803 - IV 1 ug/kg | Characterization of the Pharmacokinetic Profile - Vss Volume of Distribution at Steady State | 126 mL/kg |
| Cohort 2: N-803 - IV 3 ug/kg | Characterization of the Pharmacokinetic Profile - Vss Volume of Distribution at Steady State | 71.8 mL/kg |
| Cohort 3: N-803 - IV 6 ug/kg | Characterization of the Pharmacokinetic Profile - Vss Volume of Distribution at Steady State | 34.0 mL/kg |
| Cohort 4: N-803 - IV 10 ug/kg | Characterization of the Pharmacokinetic Profile - Vss Volume of Distribution at Steady State | 62.8 mL/kg |
Secondary
Immunogenicity - Anti-drug Antibody (ADA)
Number of patients with a positive Anti-drug Antibody (ADA) result
Time frame: From Baseline up to Week 12
Population: Cohort 7: N-803 - SQ 20 ug/kg did not enroll any subjects
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: N-803 - IV 1 ug/kg | Immunogenicity - Anti-drug Antibody (ADA) | 0 Participants |
| Cohort 2: N-803 - IV 3 ug/kg | Immunogenicity - Anti-drug Antibody (ADA) | 0 Participants |
| Cohort 3: N-803 - IV 6 ug/kg | Immunogenicity - Anti-drug Antibody (ADA) | 0 Participants |
| Cohort 4: N-803 - IV 10 ug/kg | Immunogenicity - Anti-drug Antibody (ADA) | 0 Participants |
| Cohort 5: N-803 - SQ 10 ug/kg | Immunogenicity - Anti-drug Antibody (ADA) | 0 Participants |
| Cohort 6: N-803 - SQ 15 ug/kg | Immunogenicity - Anti-drug Antibody (ADA) | 0 Participants |