Phase 2
N=310
A Study of Atezolizumab in Participants With Locally Advanced or Metastatic Urothelial Bladder Cancer (Cohort 2)
Bladder Cancer
Bottom Line
View on ClinicalTrials.gov: NCT02108652 ↗Enrolled (actual)
310
Serious AEs
50.0%
Results posted
Jan 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 Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) — 15.8 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 Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) |
15.8 | — |
| PRIMARY Percentage of Participants With a Confirmed Objective Response of CR or PR as Assessed by the Investigator According Modified RECIST |
19.7 | — |
| 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 |
20.50 | — |
| SECONDARY DOR as Assessed by the Investigator According to Modified RECIST |
20.50 | — |
| SECONDARY Percentage of Participants With Death or Disease Progression as Assessed by the IRF According to RECIST v1.1 |
88.4 | — |
| SECONDARY Progression-Free Survival (PFS) as Assessed by the IRF According to RECIST v1.1 |
2.10 | — |
| SECONDARY Percentage of Participants With Death or Disease Progression as Assessed by the Investigator According to RECIST v1.1 |
89.7 | — |
| SECONDARY PFS as Assessed by the Investigator According to RECIST v1.1 |
2.10 | — |
| SECONDARY Percentage of Participants With Death or Disease Progression as Assessed by the Investigator According to Modified RECIST |
87.1 | — |
| SECONDARY PFS as Assessed by the Investigator According to Modified RECIST |
2.56 | — |
| SECONDARY Percentage of Participants With a Confirmed Objective Response of CR or PR as Assessed by the Investigator According RECIST v1.1 |
16.5 | — |
| SECONDARY Percentage of Participants Who Died |
72.9 | — |
| SECONDARY Overall Survival (OS) |
7.9 | — |
| SECONDARY Percentage of Participants Alive at 1-year |
36.9 | — |
| SECONDARY Maximum Serum Concentration (Cmax) of Atezolizumab |
364 | — |
| SECONDARY Minimum Serum Concentration (Cmin) of Atezolizumab |
0.0252; 74.2; 120.0; 147.0; 188.0 | — |
| SECONDARY Percentage of Participants Positive for Anti-therapeutic Antibodies (ATA) to Atezolizumab |
42.4 | — |
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 will consist of participants who are treatment-naïve and ineligible for cisplatin-containing chemotherapy. The results of Cohort 1 are reported separately (NCT02951767). Cohort 2 (reported here) will contain participants who have progressed during or following a prior platinum-based chemotherapy regimen. 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 2-Specific Inclusion Criteria
- Disease progression during or following treatment with at least one platinum-containing regimen (e.g., gemcitabine and cisplatin [GC], methotrexate, vinblastine, doxorubicin, and cisplatin [MVAC], CarboGem, etc.) for inoperable locally advanced or metastatic urothelial carcinoma or disease recurrence.
- A regimen was defined as participants receiving at least two cycles of a platinum-containing regimen. Participants who had received one cycle of a platinum-containing regimen but discontinued due to Grade 4 hematologic toxicity or Grade 3 or 4 non-hematologic toxicity could also be eligible.
- Participants who received prior adjuvant/neoadjuvant chemotherapy and progressed within 12 months of treatment with a platinum-containing adjuvant/neoadjuvant regimen were considered as second-line participants.
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 (NCT02108652). 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.