Urothelial carcinoma (UC) MedDRA version: 20.0 Level: LLT Classification code 10064467 Term: Urothelial carcinoma System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Tecentriq
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: atezolizumab
CAS Number: 1380723-44-3
Other descriptive name: ATEZOLIZUMAB
Concentration unit: mg/
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Stage 1 - Age >= 18 years - Life expectancy >= 3 months, as determined by the investigator - Histologically documented, locally advanced or metastatic UC (M1, Stage IV) o Patients with mixed histologies are required to have a dominant transitional cell pattern o Locally advanced bladder cancer must be inoperable on the basis of involvement of pelvic sidewall or adjacent viscera or bulky nodal metastasis - Availability of a representative tumor specimen that is suitable for determination of PD-L1 and/or additional biomarker status by means of central testing - Disease progression during or following treatment with no more than one platinum-containing regimen for inoperable, locally advanced or metastatic UC or disease recurrence Stage 1 and Stage 2 - Ability to comply with the study protocol, in the investigator's judgment - Eastern Cooperative Oncology Group Performance Status of 0 or 1 - Measurable disease according to Response Evaluation Criteria in Solid Tumors, Version 1.1 - Adequate hematologic and end-organ function - For patients receiving therapeutic anticoagulation: stable anticoagulant regimen during the 14 days prior to Cycle (C) 1, Day (D) 1 - Negative HIV test at screening - Negative total hepatitis B core antibody (HBcAb) test, or positive total HBcAb test followed by quantitative hepatitis B virus (HBV) DNA =65 years) yes F.1.3.1 Number of subjects for this age range 213
Exclusion criteria
Exclusion criteria: Stage 1 - Prior treatment with a T-cell co-stimulating therapy or an immune checkpoint inhibitor including anti- CTLA-4 anti-PD-1, and anti-PD-L1 therapeutic antibodies - Prior treatment with any of the protocol-specified study treatments including treatment with any poly (ADP-ribose) polymerase inhibitor, nectin-4 targeting agents, signal regulatory protein a-targeting agents, or agents that block CD38 - Treatment with investigational therapy within 28 days prior to C1D1 - Any approved anti-cancer therapy within 3 weeks prior to initiation of study treatment - Eligible only for the control arm Stage 1 and Stage 2 - Prior allogeneic stem cell or solid organ transplantation - Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the drug prior to the C1D1 - Treatment with systemic immunosuppressive medication within 2 weeks prior to C1D1, or anticipation of need for systemic immunosuppressant medication during study treatment - Treatment with a live, attenuated vaccine within 4 weeks prior to C1D1, or anticipation of need for such a vaccine during Atezo treatment or within 5 months after the last dose of Atezo - Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures - Uncontrolled tumor-related pain - Uncontrolled or symptomatic hypercalcemia - Symptomatic, untreated or actively progressing central nervous system metastases - History of leptomeningeal disease - Active or history of autoimmune disease, idiopathic pulmonary fibrosis, organizing pneumonia drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan - History of malignancy other than UC within 2 years prior to screening - Active tuberculosis (TB) - Severe infection within 4 weeks prior to C1D1 - Treatment with therapeutic oral or intravenous (IV) antibiotics within 2 weeks prior to C1D1 - Significant cardiovascular disease - Grade >=3 hemorrhage or bleeding event within 28 days prior to C1D1 - Major surgical procedure, other than for diagnosis, within 4 weeks prior to C1D1, or anticipation of need for a major surgical procedure during study - Adverse events from prior anti-cancer therapy that have not improved to Grade = 2 - Active keratitis or corneal ulcerations - Uncontrolled diabetes - AST or ALT > = 3.0 x ULN - Evidence of active keratitis or corneal ulcerations during Stage 1 ophthalmologic examination prior to C1D1will be re-assigned to the control arm - Patients entering Stage 2: evidence of active keratitis or corneal ulcerations during the Stage 2 ophthalmologic examination prior to C1D1 For Atezo- niraparib (Nira) Arm during Stage 1 - Inability to swallow medication or a malabsorption condition that would alter the absorption of orally administered medications - Patients with unco
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To evaluate the efficacy of immunotherapy-based treatment combinations during Stage 1 based on Objective response rate;Secondary Objective: • To evaluate the efficacy of immunotherapy-based treatment combinations during Stage 1 based on progression-free survival, overall survival, overall survival rate, duration of response, disease control •To evaluate the safety of immunotherapy-based treatment combinations during Stage 1 •To characterize the pharmacokinetic (PK) profile of drugs that are administered as part of an immunotherapy based treatment combination during Stage 1 •To evaluate the immune response to drugs that are administered as part of an immunotherapy-based treatment combination during Stage 1 ;Primary end point(s): 1. Objective response rate;Timepoint(s) of evaluation of this end point: 1. Up to 5 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Progression-free survival 2. Overall survival 3. Overall survival rate at specific time points 4. Duration of response 5. Disease control 6. Incidence, nature, and severity of adverse events and laboratory abnormalities, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 7. Change from baseline in vital signs 8. Change from baseline in targeted clinical laboratory test results 9. Plasma or serum concentration of each drug at specified time points 10. For drugs for which anti-drug antibody (ADA) formation is measured: presence of ADAs during the study relative to the presence of ADAs at baseline ;Timepoint(s) of evaluation of this end point: 1-2. Up to 5 years 3. Up to 5 years (yearly) 4-6. Up to 5 years 7-8. Baseline (Day [D] 1, Cycle [C] 1) to 5 years 9-10. Atezo Control Arm, Atezo-EV Arm, Atezo+ Nira (Preliminary Phase): D1 of C 1, 2, 4, 8, 12, 16 + treatment discontinuation (TD) visit Atezo-EV Arm (Expansion Phase): D1, 8 of C1, D1 of C2, 4, 8, 12, 16, TD visit Atezo + Nira (Expansion Phase) and Atezo + Lina Arm: D1, 15 of C1; D1 of C2, 4, 8, 12, 16, TD visit Atezo + Hu5F9-G4 Arm: D1, 8, 22 of C1; D1 of C2, 4, 8, 12, 16, TD visit Atezo + isatuximab (Isa) Arm (Preliminary Phase): D1 of C1, 2, 4, 6, 8, 10, 12, 16, TD visit Atezo + Isa Arm (Expansion Phase): D1, 8, 15 of C1; D1 of C2, 3, 4, 6, 8, 10, 12, 16, TD visit Atezo + TCZ Arm: D1 of C1, 2, 4, 6, 8, 10, 12, 14, 16; every fourth cycle after cycle 16, TD visit | — |
Countries
France, Greece, Korea, Republic of, Spain, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd
Outcome results
None listed