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Phase 3 N=1,213 Randomized Double-blind Treatment

Study of Atezolizumab as Monotherapy and in Combination With Platinum-Based Chemotherapy in Participants With Untreated Locally Advanced or Metastatic Urothelial Carcinoma

Urothelial Carcinoma

Enrolled (actual)
1,213
Serious AEs
50.5%
Results posted
Dec 2023
Primary outcome: Primary: Investigator Assessed Progression-Free Survival (PFS) in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm Versus Atezolizumab +Gemcitabine+Carboplatin/Cisplatin Arm — 6.34; 8.18 Months — p=0.0073

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
Atezolizumab (Drug); Carboplatin (Drug); Gemcitabine (Drug); Placebo (Other); Cisplatin (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
Hoffmann-La Roche
Primary completion
Aug 2022

Outcome Measures

OutcomeResultp-value
PRIMARY
Investigator Assessed Progression-Free Survival (PFS) in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm Versus Atezolizumab +Gemcitabine+Carboplatin/Cisplatin Arm
6.34; 8.18 0.0073 sig
PRIMARY
Overall Survival (OS) in Atezolizumab+Gemcitabine+Carboplatin/Cisplatin Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm
13.44; 16.13 0.0230 sig
PRIMARY
Overall Survival (OS) in Atezolizumab Monotherapy Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm
13.34; 15.21 0.3968
SECONDARY
Objective Response Rate (ORR) in Atezolizumab+Gemcitabine+Carboplatin/Cisplatin Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm
44.8; 48.1
SECONDARY
Objective Response Rate (ORR) in Atezolizumab Monotherapy Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm
44.4; 24.2
SECONDARY
Duration of Response (DOR) in Atezolizumab+Gemcitabine+Carboplatin/Cisplatin Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm
8.15; 9.13
SECONDARY
Duration of Response (DOR) in Atezolizumab Monotherapy Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm
8.11; 29.63
SECONDARY
IRF-PFS
6.34; 7.10 0.0373 sig
SECONDARY
OS Event Free Rate Atezolizumab+Gemcitabine+Carboplatin/Cisplatin Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm
55.00; 60.00 0.1509
SECONDARY
OS Event Free Rate in Atezolizumab Monotherapy Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm
54.56; 57.91 0.3761
SECONDARY
PFS Event Free Rate
22.17; 30.47 0.0083 sig
SECONDARY
Time to Deterioration in Global Health Status as Measured by the EORTC QLQ-C30 Score in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm Versus Atezolizumab +Gemcitabine+Carboplatin/Cisplatin Arm
12.06; 32.07 0.0542
SECONDARY
Time to Deterioration in Global Health Status as Measured by the EORTC QLQ-C30 Score in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm Versus Atezolizumab Monotherapy Arm
12.02; 23.20 0.6139
SECONDARY
Time to Deterioration in Physical Function as Measured by the EORTC QLQ-C30 Score in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm Versus Atezolizumab +Gemcitabine+Carboplatin/Cisplatin Arm
15.74; 16.39 0.5540
SECONDARY
Time to Deterioration in Physical Function as Measured by the EORTC QLQ-C30 Score in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm Versus Atezolizumab Monotherapy Arm
16.10; 9.23 0.0241 sig
SECONDARY
Maximum Atezolizumab Serum Concentration
379; 390
SECONDARY
Minimum Atezolizumab Serum Concentration
79.8; 80.2; 122; 129; 153; 157
SECONDARY
Percentage of Participants With Anti-Therapeutic (Anti-Atezolizumab) Antibodies (ATAs)
1.2; 0.9; 19.7; 26.3
SECONDARY
Investigator-Assessed Progression-Free Survival (INV-PFS) in Participants Treated With Atezolizumab Monotherapy Arm Compared With Placebo+Gemcitabine+Carboplatin/Cisplatin Arm
6.31; 2.69 1.0000
SECONDARY
Percentage of Participants With Grade 3-4 Adverse Events (AEs)
84.1; 84.6; 46.3
SECONDARY
Percentage of Participants With Grade 5 Adverse Events (AEs)
7.5; 5.7; 7.9
SECONDARY
Percentage of Participants With Serious Adverse Events (SAEs)
53.7; 50.6; 46.0
SECONDARY
Percentage of Participants With Adverse Events (AEs) Leading to Withdrawal of Any Study Treatment
36.3; 33.9; 9.0
SECONDARY
Percentage of Participants With Atezolizumab-Specific Adverse Events of Special Interest (AESIs)
53.3; 35.5; 39.5

Summary

A Phase III, randomised study of atezolizumab alone and in combination with chemotherapy versus chemotherapy alone in participants with untreated advanced urothelial cancer.

Eligibility Criteria

Inclusion Criteria

  • Considered to be eligible to receive platinum-based chemotherapy, in the investigator's judgment
  • Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to ( ) 12 months between the last treatment administration and the date of recurrence is required in order to be considered treatment naive in the metastatic setting
  • Prior local intravesical chemotherapy or immunotherapy is allowed if completed at least 4 weeks prior to the initiation of study treatment
  • Measurable disease, as defined by RECIST v1.1
  • Adequate hematologic and end-organ function
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of /=4 weeks since completion of radiotherapy or surgical resection and >/=2 weeks since discontinuation of corticosteroids
  • Prior treatment with CD137 agonists, anti-CTLA-4, anti-programmed death-1 (PD-1), or anti-PD-L1 therapeutic antibody or pathway-targeting agents
  • Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [TNF] agents) within 2 weeks prior to Cycle 1, Day 1 or anticipated requirement for systemic immunosuppressive medications during the study
  • Leptomeningeal disease
  • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
  • Uncontrolled tumour-related pain or hypercalcemia
  • Significant cardiovascular disease including known left ventricular ejection fraction (LVEF) <40%
  • Severe infections within 4 weeks before randomization or therapeutic oral or IV antibiotics within 2 weeks before randomization
  • Major surgical procedure within 4 weeks prior to randomization or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis
  • Malignancies other than urothelial carcinoma within 5 years prior to Cycle 1, Day 1
  • Life expectancy of <12 weeks
  • Pregnant or lactating, or intending to become pregnant during the study
  • Serum albumin <25 gram per liter (g/L)
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  • Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
  • History of autoimmune disease
  • Participants with prior allogeneic stem cell or solid organ transplantation
  • History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan
  • Positive test for human immunodeficiency virus (HIV)
  • Active hepatitis B or hepatitis C
  • Active tuberculosis
  • Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02807636). 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.

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