Safety and Pharmacology Study of Atezolizumab Alone and in Combination With Bacille Calmette-Guérin (BCG) in High-Risk Non-Muscle-Invasive Bladder Cancer (NMIBC) Participants

Conditions

• Bladder Cancer

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Atezolizumab — DRUG
  Atezolizumab will be administered as per the schedule specified in respective arm.
• Bacille Calmette-Guérin — BIOLOGICAL
  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).

Study Details

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.

Key Dates

Start date

Jun 13, 2016

Status verified

Sep 2021

Primary completion

Sep 29, 2020

Completion

Sep 29, 2020

Study Design

Enrollment

24 participants (actual)

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Cohort 1A: Atezolizumab (BCG-unresponsive NMIBC)
  Participants will receive atezolizumab 1200 mg IV infusion q3w, for a maximum of 32 doses or 96 weeks of therapy, whichever comes first.
• Experimental: Cohort 1B: Atezolizumab + BCG (BCG-unresponsive NMIBC)
  During BCG induction course (12 weeks), participants will receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants will receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. Optional BCG maintenance courses 2-5 (each 24 weeks), participants will receive atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.
• Experimental: Cohort 2: Atezolizumab + BCG (BCG-relapsing NMIBC)
  During BCG induction course (12 weeks), participants will receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants will receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. During BCG maintenance courses 2-5 (each 24 weeks), participants will receive atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.
• Experimental: Cohort 3: Atezolizumab + BCG (BCG-naive NMIBC)
  During BCG induction course (12 weeks), participants will receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of six doses. During BCG maintenance course 1 (12 weeks), participants will receive atezolizumab 1200 mg IV infusion q3w for a total of four doses plus BCG at the assigned dose weekly for a total of three doses. During BCG maintenance courses 2-5 (each 24 weeks), participants will receive atezolizumab 1200 mg IV infusion q3w for a total of eight doses per course plus BCG at the assigned dose weekly for a total of three doses per course.

Primary Outcome Measure

Percentage of Participants With Adverse Events [ Time Frame: From Baseline up to end of study (up to approximately 4.3 years) ]

Locations (8)

Find similar trials in Stanford, CA

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