PK Sub-Study of QUILT-3.032 (CA ALT-803-01-16) and of QUILT-2.005 (CA ALT-803-01-14)
Study Details
Study Description
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)
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Cohort A: CIS (either study) Patients with histologically confirmed presence of BCG-unresponsive CIS, [with or without Ta/T1 papillary disease]. |
Biological: BCG in Combination with N-803
BCG in Combination with N-803
Other Names:
|
| Cohort B: High-Grade Ta/T1 Papillary Disease (either study) Patients with histologically confirmed presence of BCG-unresponsive high-grade Ta/T1 papillary disease |
Biological: BCG in Combination with N-803
BCG in Combination with N-803
Other Names:
|
| Cohort C: CIS (QUILT-3.032) Patients with histologically confirmed presence of BCG-unresponsive CIS, [with or without Ta/T1 papillary disease]. |
Drug: N-803 alone
N-803 alone
|
Outcome Measures
Primary Outcome Measures
- PK Parameter [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)
- PK Parameter [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)
- PK Parameter [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)
- PK Parameter [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)
- PK Parameter [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)
- PK Parameter [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)
- PK Parameter [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)
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | UCLA Department of Urology | Los Angeles | California | United States | 90024 |
| 2 | University of Miami Miller School of Medicine-Sylvester Comprehensive Cancer Center | Miami | Florida | United States | 33136 |
| 3 | Adult & Pediatric Urology | Omaha | Nebraska | United States | 68114 |
| 4 | NYU Winthrop University Hospital Department of Urology | Garden City | New York | United States | 11530 |
| 5 | Manhattan Medical Research | New York | New York | United States | 10016 |
| 6 | Virginia Urology | Richmond | Virginia | United States | 23235 |
Sponsors and Collaborators
- Altor BioScience
Investigators
- Study Director: Chad Garner, PhD, ImmunityBio, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- QUILT-3.032-2.005-PK