Pharmacokinetics
Conditions
Brief summary
Non-interventional PK sub-study of QUILT-3.032 (CA-ALT-803-01-16) and QUILT-2.005 (CA-ALT-803-01-14)
Detailed description
QUILT-3.032 is a Phase 2, open-label, single-arm, three-cohort, multicenter study of intravesical BCG plus ALT-803 in patients with BCG unresponsive high grade NMIBC. Patients will be enrolled into one of three study cohorts. Cohort A will enroll 80 patients who have histologically confirmed presence of BCG-unresponsive carcinoma in situ (CIS) \[with or without Ta or T1 disease\]. Cohort B will enroll 80 patients who have histologically confirmed BCG-unresponsive high-grade Ta or T1 disease. Cohort C will enroll up to 23 patients who also have histologically confirmed presence of BCG-unresponsive CIS \[with or without Ta/T1 papillary disease\]. Patients in Cohorts A and B will receive ALT-803 plus BCG combination treatment. Patients in Cohort C will receive ALT-803 alone. Enrollment of Cohort C will start once the enrollment of Cohort A is complete. Cohorts A, B, and C are independent study cohorts and will be separately evaluated for efficacy. All patients treated in the study will receive via a urinary catheter in the bladder, BCG plus ALT-803 or ALT-803 alone weekly for 6 consecutive weeks during the induction treatment period. QUILT-2.005 is a phase 2b, randomized, two-cohort, open-label, multicenter study of intravesical ALT-803 plus BCG versus BCG alone, in BCG naïve patients with high-grade NMIBC. Patients will be enrolled into one of two study cohorts and randomized into two arms to be treated with either ALT-803 plus BCG or BCG alone. Cohort A will initially enroll 366 patients who have histologically confirmed CIS (with or without Ta/T1 papillary disease). Cohort B will initially enroll 230 patients who have histologically confirmed high-grade papillary Ta/T1 disease only. Cohorts A and B are two independent study cohorts and will be evaluated separately for efficacy. PK sub-study: Blood samples to determine serum levels of ALT-803 will be collected on study day 1 prior to dosing, and at post-bladder voiding (+ 15 minutes), 24 (±2), 48 (±4), 72 (±4), 96 (±4) and 168 (±4) hours after dosing administered at study Week 1 and again at the same time points for study Week 6. Six subjects from either cohort A (either study) or cohort C (QUILT 3.032) and six subjects from cohort B (either study) will be sampled initially. Up to an additional 4 subjects for each cohort may also be sampled. Patients enrolled in QUILT 2.005 must have been randomized to receive ALT-803 plus BCG to be eligible for the PK sub-study.
Interventions
BIOLOGICALBCG in Combination with N-803
BCG in Combination with N-803
DRUGN-803 alone
N-803 alone
Sponsors
Altor BioScience
Study design
Observational model
COHORT
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Only subjects who are eligible for and have entered into protocol QUILT-3.032 or QUILT-2.005 may participate in this sub-study. * Patients enrolled in QUILT-2.005 must have been randomized to receive ALT-803 plus BCG to participate in this sub-study.
Exclusion criteria
* Refusal to provide voluntary written informed consent and HIPAA authorization and agree to comply with all protocol-specified procedures and follow-up evaluations. * Loss of ≥ 475 mL blood volume or blood transfusion of any blood product within 3 months prior to screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Half-life (t½) | Study day 1 prior to dosing, and at post-bladder voiding (+ 15 minutes), 24 (±2), 48 (±4), 72 (±4), 96 (±4) and 168 (±4) hours after dosing administered at study Week 1 and again at the same time points for study Week 6. | Half-life (t½) |
| Apparent (Extravascular) Volume of Distribution (Vz/F) | Study day 1 prior to dosing, and at post-bladder voiding (+15 minutes), 24 (±2), 48 (±4), 72 (±4), 96 (±4) and 168 (±4) hours after dosing administered at study Week 1 and again at the same time points for study Week 6. | Apparent (extravascular) volume of distribution (Vz/F) |
| Apparent (Extravascular) Clearance (CL/F) | Study day 1 prior to dosing, and at post-bladder voiding (+ 15 minutes), 24 (±2), 48 (±4), 72 (±4), 96 (±4) and 168 (±4) hours after dosing administered at study Week 1 and again at the same time points for study Week 6. | Apparent (extravascular) clearance (CL/F) |
| Maximum Observed Concentration (Cmax) | Study day 1 prior to dosing, and at post-bladder voiding (+ 15 minutes), 24 (±2), 48 (±4), 72 (±4), 96 (±4) and 168 (±4) hours after dosing administered at study Week 1 and again at the same time points for study Week 6. | Maximum observed concentration (Cmax) |
| Time of the Observed Maximum Concentration (Tmax) | Study day 1 prior to dosing, and at post-bladder voiding (+ 15 minutes), 24 (±2), 48 (±4), 72 (±4), 96 (±4) and 168 (±4) hours after dosing administered at study Week 1 and again at the same time points for study Week 6. | Time of the observed maximum concentration (Tmax) |
| Area Under the Plasma Concentration Curve From Time 0 Through the Last Measurable Concentration (AUC0-t) | Study day 1 prior to dosing, and at post-bladder voiding (+ 15 minutes), 24 (±2), 48 (±4), 72 (±4), 96 (±4) and 168 (±4) hours after dosing administered at study Week 1 and again at the same time points for study Week 6. | Area under the plasma concentration curve from time 0 through the last measurable concentration (AUC0-t) |
| Area Under the Plasma Concentration Curve From Time 0 Extrapolated to Infinite Time (AUC0-inf) | Study day 1 prior to dosing, and at post-bladder voiding (+ 15 minutes), 24 (±2), 48 (±4), 72 (±4), 96 (±4) and 168 (±4) hours after dosing administered at study Week 1 and again at the same time points for study Week 6. | Area under the plasma concentration curve from time 0 extrapolated to infinite time (AUC0-inf) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort A: CIS (Either Study) Patients with histologically confirmed presence of BCG-unresponsive CIS, \[with or without Ta/T1 papillary disease\].
BCG in Combination with N-803: BCG in Combination with N-803 | 1 |
| Cohort B: High-Grade Ta/T1 Papillary Disease (Either Study) Patients with histologically confirmed presence of BCG-unresponsive high-grade Ta/T1 papillary disease
BCG in Combination with N-803: BCG in Combination with N-803 | 0 |
| Cohort C: CIS (QUILT-3.032) Patients with histologically confirmed presence of BCG-unresponsive CIS, \[with or without Ta/T1 papillary disease\].
N-803 alone: N-803 alone | 0 |
| Total | 1 |
Baseline characteristics
| Characteristic | Cohort A: CIS (Either Study) | Total | Cohort C: CIS (QUILT-3.032) | Cohort B: High-Grade Ta/T1 Papillary Disease (Either Study) |
|---|---|---|---|---|
| Age, Continuous | 73 years | 73 years | — | — |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Non-muscle invasive bladder cancer enrolled on either QUILT-3.032 or QUILT-2.005 | 1 Participants | 1 Participants | 0 Participants | 0 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 | 0 Participants | 0 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 | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 | 0 / 0 |
Outcome results
Primary
Apparent (Extravascular) Clearance (CL/F)
Apparent (extravascular) clearance (CL/F)
Time frame: Study day 1 prior to dosing, and at post-bladder voiding (+ 15 minutes), 24 (±2), 48 (±4), 72 (±4), 96 (±4) and 168 (±4) hours after dosing administered at study Week 1 and again at the same time points for study Week 6.
Population: Systemic N-803 was below the limit of quantitation for all subjects at all time points assessed. Following intravesical administration, there was no evidence of systemic N-803 in any subject. PK parameters were not calculated.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cohort A: CIS (Either Study) | Apparent (Extravascular) Clearance (CL/F) | NA L/day/kg |
Primary
Apparent (Extravascular) Volume of Distribution (Vz/F)
Apparent (extravascular) volume of distribution (Vz/F)
Time frame: Study day 1 prior to dosing, and at post-bladder voiding (+15 minutes), 24 (±2), 48 (±4), 72 (±4), 96 (±4) and 168 (±4) hours after dosing administered at study Week 1 and again at the same time points for study Week 6.
Population: Systemic N-803 was below the limit of quantitation for all subjects at all time points assessed. Following intravesical administration, there was no evidence of systemic N-803 in any subject. PK parameters were not calculated.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cohort A: CIS (Either Study) | Apparent (Extravascular) Volume of Distribution (Vz/F) | NA mL/kg |
Primary
Area Under the Plasma Concentration Curve From Time 0 Extrapolated to Infinite Time (AUC0-inf)
Area under the plasma concentration curve from time 0 extrapolated to infinite time (AUC0-inf)
Time frame: Study day 1 prior to dosing, and at post-bladder voiding (+ 15 minutes), 24 (±2), 48 (±4), 72 (±4), 96 (±4) and 168 (±4) hours after dosing administered at study Week 1 and again at the same time points for study Week 6.
Population: Systemic N-803 was below the limit of quantitation for all subjects at all time points assessed. Following intravesical administration, there was no evidence of systemic N-803 in any subject. PK parameters were not calculated.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cohort A: CIS (Either Study) | Area Under the Plasma Concentration Curve From Time 0 Extrapolated to Infinite Time (AUC0-inf) | NA Day*pg/mL |
Primary
Area Under the Plasma Concentration Curve From Time 0 Through the Last Measurable Concentration (AUC0-t)
Area under the plasma concentration curve from time 0 through the last measurable concentration (AUC0-t)
Time frame: Study day 1 prior to dosing, and at post-bladder voiding (+ 15 minutes), 24 (±2), 48 (±4), 72 (±4), 96 (±4) and 168 (±4) hours after dosing administered at study Week 1 and again at the same time points for study Week 6.
Population: Systemic N-803 was below the limit of quantitation for all subjects at all time points assessed. Following intravesical administration, there was no evidence of systemic N-803 in any subject. PK parameters were not calculated.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cohort A: CIS (Either Study) | Area Under the Plasma Concentration Curve From Time 0 Through the Last Measurable Concentration (AUC0-t) | NA Day*pg/mL |
Primary
Half-life (t½)
Half-life (t½)
Time frame: Study day 1 prior to dosing, and at post-bladder voiding (+ 15 minutes), 24 (±2), 48 (±4), 72 (±4), 96 (±4) and 168 (±4) hours after dosing administered at study Week 1 and again at the same time points for study Week 6.
Population: Systemic N-803 was below the limit of quantitation for all subjects at all time points assessed. Following intravesical administration, there was no evidence of systemic N-803 in any subject. PK parameters were not calculated.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cohort A: CIS (Either Study) | Half-life (t½) | NA Hours |
Primary
Maximum Observed Concentration (Cmax)
Maximum observed concentration (Cmax)
Time frame: Study day 1 prior to dosing, and at post-bladder voiding (+ 15 minutes), 24 (±2), 48 (±4), 72 (±4), 96 (±4) and 168 (±4) hours after dosing administered at study Week 1 and again at the same time points for study Week 6.
Population: Systemic N-803 was below the limit of quantitation for all subjects at all time points assessed. Following intravesical administration, there was no evidence of systemic N-803 in any subject. PK parameters were not calculated.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cohort A: CIS (Either Study) | Maximum Observed Concentration (Cmax) | NA pg/mL |
Primary
Time of the Observed Maximum Concentration (Tmax)
Time of the observed maximum concentration (Tmax)
Time frame: Study day 1 prior to dosing, and at post-bladder voiding (+ 15 minutes), 24 (±2), 48 (±4), 72 (±4), 96 (±4) and 168 (±4) hours after dosing administered at study Week 1 and again at the same time points for study Week 6.
Population: Systemic N-803 was below the limit of quantitation for all subjects at all time points assessed. Following intravesical administration, there was no evidence of systemic N-803 in any subject. PK parameters were not calculated.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cohort A: CIS (Either Study) | Time of the Observed Maximum Concentration (Tmax) | NA Days |