PK Sub-Study of QUILT-3.032 (CA ALT-803-01-16) and of QUILT-2.005 (CA ALT-803-01-14)

Terminated

Conditions: Pharmacokinetics

Interventions: Biological: BCG in Combination with N-803
Drug: N-803 alone

Registration Number: NCT04142359

Lead Sponsor: Altor BioScience

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 1

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.

Study & Design

Study Type: OBSERVATIONAL

Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Cohort A: CIS (either study)	BCG in Combination with N-803	Patients with histologically confirmed presence of BCG-unresponsive CIS, \[with or without Ta/T1 papillary disease\].
Cohort B: High-Grade Ta/T1 Papillary Disease (either study)	BCG in Combination with N-803	Patients with histologically confirmed presence of BCG-unresponsive high-grade Ta/T1 papillary disease
Cohort C: CIS (QUILT-3.032)	N-803 alone	Patients with histologically confirmed presence of BCG-unresponsive CIS, \[with or without Ta/T1 papillary disease\].

Primary Outcome Measures

Name	Time	Method
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)

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (6): Adult & Pediatric Urology
🇺🇸
Omaha, Nebraska, United States
University of Miami Miller School of Medicine-Sylvester Comprehensive Cancer Center
🇺🇸
Miami, Florida, United States
UCLA Department of Urology
🇺🇸
Los Angeles, California, United States
NYU Winthrop University Hospital Department of Urology
🇺🇸
Garden City, New York, United States
Virginia Urology
🇺🇸
Richmond, Virginia, United States
Manhattan Medical Research
🇺🇸
New York, New York, United States