This Phase Ib/II study is designed to assess the safety, tolerability, pharmacokinetics, immunogenicity, patient reported outcomes (PROs), and preliminary anti-tumor activity of atezolizumab administered by intravenous (IV) infusion alone and in combination with intravesical BCG in high-risk NMIBC participants. The study will be conducted in following cohorts: Cohort 1A, Cohort 1B, Cohort 2, and Cohort 3. Atezolizumab will be administered at a fixed dose of 1200 milligrams (mg) every 3 weeks (q3w) for a maximum of 96 weeks. BCG will be administered to evaluate dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), or maximum administered dose (MAD). De-escalation will be allowed for up to three dose levels of BCG (full dose \[50 mg\], 66 percent \[%\] of a full dose, and 33% of a full dose \[Cohort 1B only\]). After the MTD or MAD is determined for Cohort 1B, this dose will be used for all subsequent participants enrolled into Cohorts 1B, 2, and 3, unless the MTD is determined to be 33% of a full BCG dose. If MTD is determined to be 33% of a full BCG dose, then, no participants will be enrolled into Cohorts 2 and 3 until an assessment of the safety and activity of the combination of atezolizumab plus 33% of a full BCG dose is completed.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Atezolizumab will be administered as per the schedule specified in respective arm.
For Cohort 1B, BCG will be administered (intravesically) at de-escalated doses. De-escalation will be allowed for up to three dose levels of BCG: full dose (50 mg), 66% of full dose, and 33% of full dose. After the MTD or MAD is determined for Cohort 1B, MTD/MAD will be used for all subsequent participants enrolled into Cohorts 1B, 2, and 3 (provided MAD or MTD is determined to be either full dose or 66% of a full BCG dose).
Stanford Univ.
Stanford, California, United States
University of Chicago Medical Center
Chicago, Illinois, United States
Johns Hopkins Kimmel Cancer Center, Office of Research Administration
Baltimore, Maryland, United States
The Montefiore Medical Center & The Albert Einstein College of Medicine; Department of Urology
The Bronx, New York, United States
Duke University
Durham, North Carolina, United States
Ohio State University
Columbus, Ohio, United States
Oklahoma University Health Sciences Center
Oklahoma City, Oklahoma, United States
VA Portland Healthcare System
Portland, Oregon, United States
Percentage of Participants With Adverse Events
Percentage of participants with at least one adverse event during the study.
Time frame: From Baseline up to end of study (up to approximately 4.3 years)
Cohort 1B: Percentage of Participants With DLTs of BCG
Percentage of participants with dose-limiting toxicities (DLT) of BCG in Cohort 1B.
Time frame: Days 1-21
Cohort 1B: MAD of BCG
Maximum administered dose (MAD) of BCG.
Time frame: Days 1-21
Percentage of Participants With Complete Response (CR) as Assessed by the Investigator on the Basis of Cystoscopy and Urine Cytology at Month 6
CR at 6 months after the start of study treatment as assessed by the investigator on the basis of cystoscopic assessment and urine cytology.
Time frame: 6 months
Percentage of Participants With CR as Assessed by the Investigator on the Basis of Cystoscopy and Urine Cytology at Month 3
CR at the 3-month disease assessment, evaluated by both cystoscopy and cytology.
Time frame: 3 months
Duration of CR, as Assessed on the Basis of Cystoscopy and Urine Cytology
Duration of CR will be defined for participants with a CR as the time from the first occurrence of a documented complete response to recurrence of high-grade NMIBC or death from any cause.
Time frame: From first occurence of a documented CR until the time of recurrence of NMIBC or death from any cause (up to approximately 4.3 years)
Percentage of Participants With Recurrence-Free Survival (RFS), as Assessed on the Basis of Cystoscopy and Urine Cytology
RFS rate at 6, 12, and 18 months, defined as the proportion of patients who are alive and free of persistent/recurrent high-grade NMIBC.
Time frame: 6, 12 and 18 months
Bladder-Intact Disease-Free Survival (DFS), as Assessed on the Basis of Cystoscopy and Urine Cytology
Bladder-intact DFS was defined as the time from the first study treatment to earliest evidence of progression to muscle-invasive disease in the bladder, regional pelvic progression, distant metastasis, bladder cancer-related death, or cystectomy.
Time frame: From first study treatment to earliest evidence of progression to muscle-invasive disease in the bladder, regional pelvic progression, distant metastasis, bladder cancer-related death, or cystectomy or death from any cause (up to approximately 4.3 years)
Progression-Free Survival (PFS), as Assessed on the Basis of Cystoscopy and Urine Cytology
PFS, defined as the time from the first study treatment to the first occurrence of progression to muscle-invasive disease based on cystoscopy and urine cytology or death from any cause.
Time frame: Time from first study treatment to the first occurrence of progression to muscle-invasive disease or death from any cause (up to approximately 4.3 years)
Cystectomy-Free Survival (CFS), as Assessed on the Basis of Cystoscopy and Urine Cytology
Cystectomy-free survival, defined as from start of study treatment to bladder removal for any cause or death from any cause.
Time frame: Time from first study treatment to cystectomy or death from any cause (up to approximately 4.3 years)
Overall Survival
Time frame: Time from first study treatment to death from any cause (up to approximately 4.3 years)
Maximum Observed Serum Concentration of Atezolizumab (Cmax)
Maximum observed serum concentration of Atezolizumab (Cmax)
Time frame: Cycle 1 Day 1 post-dose (Cycle length=21 days)
Minimum Observed Serum Concentration of Atezolizumab (Cmin)
Minimum observed serum concentration of atezolizumab (Cmin)
Time frame: Pre-dose (0 hr) on Day 1 of Cycles 2, 3, 4 and 8 (Cycle length=21 days)
Percentage of Participants With Anti-Therapeutic Antibody (ADA) Response to Atezolizumab
Percentage of participants with anti-therapeutic antibody (ADA) response to atezolizumab.
Time frame: Pre-dose (0 hr) on Day 1 of Cycles 1, 2, 3, 4, 8, 16, 24 (Cycle length=21 days), end of atezolizumab treatment (up to 96 weeks), 120 days after end of atezolizumab treatment (up to 113 weeks)
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