Phase 2
N=119
A Study of Atezolizumab in Participants With Locally Advanced or Metastatic Urothelial Bladder Cancer (Cohort 1)
Bladder Cancer
Bottom Line
View on ClinicalTrials.gov: NCT02951767 ↗Enrolled (actual)
119
Serious AEs
41.2%
Results posted
Apr 2017
Primary outcome: Primary: Percentage of Participants With a Confirmed Objective Response of Complete Response (CR) or Partial Response (PR) as Assessed by the Independent Review Facility (IRF) According to RECIST v1.1 — 22.7 percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Atezolizumab (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Hoffmann-La Roche
- Primary completion
- Jul 2016
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With a Confirmed Objective Response of Complete Response (CR) or Partial Response (PR) as Assessed by the Independent Review Facility (IRF) According to RECIST v1.1 |
22.7 | — |
| SECONDARY Duration of Response (DOR) as Assessed by the IRF According to RECIST v1.1 |
NA | — |
| SECONDARY DOR as Assessed by the Investigator According to RECIST v1.1 |
NA | — |
| SECONDARY Percentage of Participants With Death or Disease Progression as Assessed by the IRF According to RECIST v1.1 |
73.9 | — |
| SECONDARY Progression-Free Survival (PFS) as Assessed by the IRF According to RECIST v1.1 |
2.69 | — |
| SECONDARY Percentage of Participants With Death or Disease Progression as Assessed by the Investigator According to RECIST v1.1 |
71.4 | — |
| SECONDARY PFS as Assessed by the Investigator According to RECIST v1.1 |
4.17 | — |
| SECONDARY Percentage of Participants With a Confirmed Objective Response of CR or PR as Assessed by the Investigator According RECIST v1.1 |
25.2 | — |
| SECONDARY Percentage of Participants Who Died |
49.6 | — |
| SECONDARY Overall Survival (OS) |
15.9 | — |
| SECONDARY Percentage of Participants Alive at 1-year |
57.2 | — |
| SECONDARY Maximum Serum Concentration (Cmax) of Atezolizumab |
386 | — |
| SECONDARY Minimum Serum Concentration (Cmin) of Atezolizumab |
0; 77.7; 117; 159; 169 | — |
| SECONDARY Percentage of Participants Positive for Anti-therapeutic Antibodies (ATA) to Atezolizumab |
47.7 | — |
Summary
This Phase II, single-arm study is designed to evaluate the effect of atezolizumab treatment in participants with locally advanced or metastatic urothelial bladder cancer. Participants will be enrolled into 1 of 2 cohorts. Cohort 1 (reported here) will consist of participants who are treatment-naïve and ineligible for cisplatin-containing chemotherapy. Cohort 2 will contain participants who have progressed during or following a prior platinum-based chemotherapy regimen. The results of the second cohort are reported separately (NCT02108652). Participants in both cohorts will be given a 1200 milligrams (mg) intravenous (IV) dose of atezolizumab on Day 1 of 21-day cycles. Treatment of participants in Cohort 1 will continue until disease progression per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or unmanageable toxicity. Treatment of participants in Cohort 2 will continue until loss of clinical benefit or unmanageable toxicity.
Eligibility Criteria
Inclusion Criteria
- Histologically or cytologically documented locally advanced or metastatic transitional cell carcinoma of the urothelium (including renal pelvis, ureters, urinary bladder, urethra)
- Representative tumor specimens as specified by the protocol
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Life expectancy greater than or equal to (>=) 12 weeks
- Measurable disease, as defined by RECIST v1.1
- Adequate hematologic and end organ function
Cohort 1-Specific Inclusion Criteria
- No prior chemotherapy for inoperable locally advanced or metastatic or recurrent urothelial carcinoma
- Ineligible for cisplatin-based chemotherapy due to one of the following: Impaired renal function, a hearing loss of 25 decibels (dB) at two contiguous frequencies, Grade 2 or greater peripheral neuropathy, or ECOG performance score of 2
Exclusion Criteria
- Any approved anti-cancer therapy within 3 weeks prior to initiation of study treatment
- Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to enrollment
- Active or untreated central nervous system (CNS) metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments
- Leptomeningeal disease
- Uncontrolled tumor-related pain
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
- Uncontrolled hypercalcemia (greater than [>] 1.5 millimoles per liter [mmol/L] ionized calcium or Ca > 12 milligrams per deciliter [mg/dL] or corrected serum calcium > upper limits of normal [ULN]) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab
- Malignancies other than urothelial bladder cancer within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome or incidental prostate cancer
- Pregnant and lactating women
- History of autoimmune disease
- History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
- Serum albumin less than (<) 2.5 grams per deciliter (g/dL)
- Positive test for human immunodeficiency virus (HIV) and/or active hepatitis B or hepatitis C or tuberculosis
- Severe infections within 4 weeks prior to Cycle 1, Day 1
- Significant cardiovascular disease
- Major surgical procedure other than for diagnosis within 28 days prior to Cycle 1, Day 1
- Prior allogeneic stem cell or solid organ transplant
- Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1
- Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
- Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4), anti-programmed death-1 receptor (anti-PD-1), and anti-programmed death-ligand 1 (anti-PD-L1) therapeutic antibodies
Data sourced from ClinicalTrials.gov (NCT02951767). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.