Atezolizumab for Urothelial carcinoma | Muscle-invasive bladder cancer | Metastatic bladder cancer

Inclusion criteria

• {"criterion_text":"- ≥18 years of age at the time of signing the Informed Consent Form\n- For male Study Subjects: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm\n- Signed Informed Consent Form\n- ECOG PS 0 or 1\n- Is, according to the Investigator’s judgement, able to comply with the trial protocol\n- Ability to understand the Participant Information Sheet orally and in writing\n- Preoperative PET/CT of thorax, abdomen, and pelvis with no suspicion of organ metastases or lymph node metastasis* above the aortic bifurcation\n- Study Subjects planned to undergo radical cystectomy due to histopathological or clinical documented muscle invasive urothelial carcinoma (including subtypes) stage cT2-4a in the urinary bladder following NAC** in cisplatin-fit Study Subjects"}

Exclusion criteria

• {"criterion_text":"- Other histology of BC than urothelial carcinoma – mixed tumours with urothelial features are allowed\n- Concomitant invasive cancer within 5 years other than non-melanoma skin cancer and prostate cancer without metastasis\n- Known contraindication to immunotherapy\n- A history of autoimmune disease. Study Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease\n- Study Subjects who meet any of the following criteria will be excluded from study entry: o History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan o Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or 5 drug elimination half-lives (whichever is longer) prior to initiation of study treatment\n- HIV positive\n- History of pneumonitis (History of radiation pneumonitis in the radiation field (fibrosis) is permitted.\n- Hepatitis B or hepatitis C infection\n- Subjects who have received a live, attenuated vaccine within 28 days prior to enrolment"}

Primary endpoints

• {"endpoint_text":"- Complete response (CR) after treatment with investigational agent initiated by ctDNA positive status after radical cystectomy (with or without concomitant visible metastases on CT)","definition_or_measurement_approach":"CR in the current study is defined as ctDNA negative status in the last plasma samples taken during IO treatment combined with negative imaging (CT) at the same time point after treatment. Thus, any metastasis visible on CT at the time of treatment initiation should undergo complete response. In Study Subjects without visible metastasis on CT at the time of treatment, initiation should result in unchanged status on CT."}

Secondary endpoints

• {"endpoint_text":"- Duration of freedom from clinical relapse in Study Subjects showing decrease or stabilization of ctDNA level after treatment with investigational agent\n- Overall survival after cystectomy in Study Subjects having biochemical relapse\n- Cancer specific survival after cystectomy in Study Subjects having biochemical relapse\n- Recurrence free survival after cystectomy in Study Subjects having biochemical relapse\n- Cancer specific survival after cystectomy in Study Subjects having biochemical relapse stratified for potential predictive biomarkers for response to treatment\n- Response rate to investigated agent stratified for PD-L1 expression and other predictive biomarkers like TMB, immune cell infiltration, tumor subtypes etc.\n- Response rate to neoadjuvant chemotherapy measured as down staging to T0 or T<2 at cystectomy and correlation with level of ctDNA in plasma and urine samples\n- Time to recurrence seen on imaging (symptomatic or asymptomatic)\n- Quality of life assessment using the EORTC QLQ 30 (Quality of life in cancer patients) and QLQ-BLM30 (Quality of life in patients with Muscle Invasive Bladder Cancer)\n- Cost-effectiveness modelling analysis\n- Prolonged CR defined as ctDNA negative status in the plasma samples taken 12 months following completion of IO combined with negative imaging (CT) at the same time point, without administration of other oncologic treatment","definition_or_measurement_approach":"As stated in endpoint texts; QoL measured using EORTC QLQ-C30 and QLQ-BLM30. Other endpoints rely on ctDNA measurements, imaging (CT), survival analyses and biomarker stratification (PD-L1, TMB, immune cell infiltration, tumor subtypes)."}

Denmark

Latest Decision Or Authorization Date

16-01-2026

Number Of Sites

9

Number Of Participants

282

Primary sponsor

Full Name

Aarhus Universitetshospital

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Denmark

Third parties

• {"country":"Denmark","full_name":"Aarhus Universitet","duties_or_roles":"Codes: 1,8,9","organisation_type":"Educational Institution"}