Phase 3
N=1,213
Study of Atezolizumab as Monotherapy and in Combination With Platinum-Based Chemotherapy in Participants With Untreated Locally Advanced or Metastatic Urothelial Carcinoma
Urothelial Carcinoma
Bottom Line
View on ClinicalTrials.gov: NCT02807636 ↗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
| Outcome | Result | p-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
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.