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

A Pharmacokinetic Sub-Study of QUILT-3.032 (CA ALT-803-01-16): A Multicenter Clinical Trial of Intravesical Bacillus Calmette-Guerin (BCG) in Combination With ALT-803 in Patients With BCG Unresponsive High Grade Non-Muscle Invasive Bladder Cancer and QUILT-2.005: A Study of Intravesical BCG in Combination With ALT-803 in Patients With Non-Muscle Invasive Bladder Cancer

Non-interventional PK sub-study of QUILT-3.032 (CA-ALT-803-01-16) and QUILT-2.005 (CA-ALT-803-01-14)

Study Overview

• Status: Terminated
• Conditions: Pharmacokinetics
• Intervention / Treatment: Biological: BCG in Combination with N-803; Drug: N-803 alone

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 Type: Observational
• Enrollment (Actual): 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90024
      • UCLA Department of Urology
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine-Sylvester Comprehensive Cancer Center
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Adult & Pediatric Urology
  • New York
    • Garden City, New York, United States, 11530
      • NYU Winthrop University Hospital Department of Urology
    • New York, New York, United States, 10016
      • Manhattan Medical Research
  • Virginia
    • Richmond, Virginia, United States, 23235
      • Virginia Urology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

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 in this PK sub-study. Up to an additional 4 subjects from each cohort may also be sampled.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	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: N-803
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: N-803
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Half-life (t½)	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.
Apparent (Extravascular) Volume of Distribution (Vz/F)	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) Clearance (CL/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.
Maximum Observed Concentration (Cmax)	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.
Time of the Observed Maximum Concentration (Tmax)	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.
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)	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)	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.

Collaborators and Investigators

• Sponsor: Altor BioScience
• Investigators: Study Director: Chad Garner, PhD, ImmunityBio, Inc.

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2019
• Primary Completion (Actual): April 6, 2020
• Study Completion (Actual): April 6, 2020

Study Registration Dates

• First Submitted: October 23, 2019
• First Submitted That Met QC Criteria: October 25, 2019
• First Posted (Actual): October 29, 2019

Study Record Updates

• Last Update Posted (Estimated): December 10, 2024
• Last Update Submitted That Met QC Criteria: December 5, 2024
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: QUILT-3.032-2.005-PK

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No