A Study of Intravesical BCG in Combination With ALT-803 in Patients With Non-Muscle Invasive Bladder Cancer
- Conditions
- Non-muscle Invasive Bladder Cancer
- Interventions
- Biological: BCG( 50mg/Instillation)Biological: BCG+N-803( 50mg BCG/ Instillation+ N-803( 400 μg/instillation). )
- Registration Number
- NCT02138734
- Lead Sponsor
- ImmunityBio, Inc.
- Brief Summary
This is a Phase Ib/IIb, randomized, two-cohort, open-label, multicenter study of intravesical N-803 plus BCG versus BCG alone, in BCG naïve patients with high-grade NMIBC.
- Detailed Description
The study includes a dose escalation phase (phase Ib) and an expansion phase (phase IIb).
In the phase Ib, patients will be treated with intravesical N-803 in combination with BCG. The purpose of the phase Ib portion of the study is to evaluate the safety, identify the Maximum Tolerated Dose (MTD) of N-803 and determine the Recommended Dose (RD) level of N-803 in combination with BCG for the phase IIb expansion.
In the phase IIb expansion, patients will be randomized to receive either intravesical N-803 in combination with BCG or BCG alone. Patients will be enrolled into one of two study cohorts (Cohort A and Cohort B). These will be two independent study cohorts, evaluated separately for treatment efficacy.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 596
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description BCG alone BCG( 50mg/Instillation) (Phase IIb) for BCG-naive patients N-803+BCG BCG+N-803( 50mg BCG/ Instillation+ N-803( 400 μg/instillation). ) (Phase Ib and IIb) for BCG-naive patients
- Primary Outcome Measures
Name Time Method Complete Response (CR) Rate 6 Months Patients in Cohort A: compare complete response rate between treatment arms using cystoscopy, confirmatory bladder biopsy and urine cytology.
Disease Free Survival (DFS) 13 Years and 3 Months Patients in Cohort B: compare disease-free survival between treatment arms using
cystoscopy, confirmatory bladder biopsy and urine cytology.
- Secondary Outcome Measures
Name Time Method Cohort B: Disease Free Survival Rate 36 Months To assess DFS rate at 12, 18, 24, 30, and 36 months. The time from randomization until recurrence of high-grade Ta (excluding low grade Ta) or any grade T1, CIS, disease progression, cystectomy, change in therapy indicative of more advance disease or death (any cause), whichever occurs first.
Time to disease worsening 13 Years and 3 Months For phase IIb, Cohorts A \& B: Cystectomy or change in therapy indicative of more advanced disease, including systemic chemotherapy or radiation therapy.
Complete Response Rate( All Recurrent Bladder Cancer Including Low Grade Ta Disease) 13 Years and 3 months To assess the CR rate (all recurrent bladder cancer including low grade Ta disease) of patients treated with N-803 plus BCG compared to patients treated with BCG alone.
Duration of Complete Response ( All Recurrent Bladder Cancer Including Low Grade Ta Disease) 13 Years and 3 months Time from the date of first CR (All Recurrent bladder cancer including low grade Ta Disease) to the date of evidence that the subject no longer meets the definition for CR.
Vital signs and clinical laboratory assessment 36 Months Vital signs include heart rate, systolic and diastolic blood pressures, respiration rate, and body temperature. Labs include the following: complete blood count with differential, complete metabolic panel, and urinalysis.
Cystectomy Free Rate 13 years and 3 months Cystectomy-free rate will be calculated for each treatment group as the ratio of the number of subjects who don't have documented cystectomy in the database divided by the number of subjects in the ITT (Intent to treat) population.
Safety Profile: Number and severity of treatment emergent AEs [Time Frame: 39 Months] 39 Months For phase Ib and phase IIb: Number of participants with TEAEs as assessed by CTCAE v4.03.
Cohort B: Disease Free Survival 13 Years and 3 Months DFS was assessed in the following groups:
1) All recurrent bladder cancer, including low grade Ta disease the time from randomization until recurrence of any grade Ta (including low grade Ta) or any grade T1, CIS, disease progression, cystectomy, change in therapy indicative of more advanced disease, or death (any cause), whichever occurs first 2) Patients who have high-grade Ta, low-grade T1, or CIS at 3-months and received re-induction, and have no evidence of \> low-grade Ta disease at 6-months will be considered disease-free from randomization until a second recurrence \> low-grade Ta 3) Patients who have high-grade Ta, low-grade T1, or CIS at 3-months and received re-induction, and have no evidence of any disease (including low grade Ta) at 6-months will be considered disease-free from randomization until a second recurrence ≥ low grade Ta.Overall survival 13 Years and 3 months Time from randomization to death resulting from any cause to determine survival.
Duration of Complete Response 13 Years and 3 months To assess the duration of CR of patients treated with N-803 plus BCG compared to patients treated with BCG alone.
Long Term Complete Response Rate 13 years and 3 Months To assess the long-term CR rate (as determined by the Investigator) following completion of QUILT-2.005 phase 2b.
Long Term Follow Up(LTFU) data from subjects who were treated 10 Years after treatment period visits Yearly collection of LTFU data, which includes the following: survival status, bladder cancer status (high or low grade), cystoscopy results including number of cystoscopies done for each subject, biopsy results, upper tract evaluations, posttherapies and responses and outcomes of posttherapies, urine cytology results, and other medical history or treatments, if available, related to bladder cancer.
Progression-free survival (PFS) 13 Years and 3 Months For phase IIb, Cohorts A \& B: Time from randomization to disease progression or death.
Disease specific survival 13 Years and 3 months For phase IIb, Cohorts A \& B: Time from randomization to death resulting from bladder cancer.
Trial Locations
- Locations (25)
Skyline Sherman Oaks
🇺🇸Sherman Oaks, California, United States
Eastern Connecticut Hematology & Oncology Associates
🇺🇸Norwich, Connecticut, United States
Hoag Cancer Center
🇺🇸Irvine, California, United States
Clinical Research Center of Florida
🇺🇸Pompano Beach, Florida, United States
Skyline Urology
🇺🇸Torrance, California, United States
Manhattan Medical Research
🇺🇸New York, New York, United States
Arkansas Urology
🇺🇸Little Rock, Arkansas, United States
Kansas University Medical Center
🇺🇸Westwood, Kansas, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
University of California, Davis
🇺🇸Sacramento, California, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Adult & Pediatric Urology
🇺🇸Omaha, Nebraska, United States
Alaska Clinical Research Center
🇺🇸Anchorage, Alaska, United States
UCLA Department of Urology
🇺🇸Los Angeles, California, United States
Dartmouth-Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Winthrop University Hospital
🇺🇸Mineola, New York, United States
Urology Group of New Mexico (AccumetRx Clinical Research)
🇺🇸Albuquerque, New Mexico, United States
NYU Langone
🇺🇸New York, New York, United States
Premier Medical Group of the Hudson Valley
🇺🇸Poughkeepsie, New York, United States
Associated Urologists of North Carolina
🇺🇸Raleigh, North Carolina, United States
University of Washington School of Medicine
🇺🇸Seattle, Washington, United States
University of North Carolina Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Virginia Urology
🇺🇸Richmond, Virginia, United States
University of Hawaii Cancer Center
🇺🇸Honolulu, Hawaii, United States