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Phase 2 Completed N=119 Treatment

A Study of Atezolizumab in Participants With Locally Advanced or Metastatic Urothelial Bladder Cancer (Cohort 1)

Source: ClinicalTrials.gov NCT02951767 ↗
Enrolled (actual)
119
Serious AEs
41.2%
Results posted
Apr 2017
Primary outcomePrimary: 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

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.

Outcome Measures

OutcomeResultp-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 —

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
View full record on ClinicalTrials.gov →

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. Informational only — not medical advice.

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