Neoadjuvant Immunotherapy Combined With the Anti-GDF-15 Antibody Visugromab to Treat Muscle Invasive Bladder Cancer

Main Inclusion Criteria:

* Signed and dated informed consent, and able to comply with the study procedures and any locally required authorization.
* Male or female aged ≥ 18 years.
* Histopathologically confirmed urothelial carcinoma.
* Clinical Stage T2-T4aN0M0 MIBC.
* Ineligible for cisplatin therapy per modified Galsky criteria or refuses cisplatin-based chemotherapy.
* Eligible for radical cystectomy.
* Pretreatment tumor material from transurethral resection of the bladder tumor (TURBT) must be available.
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
* Adequate organ function (bone marrow, hepatic, renal function and coagulation).

Main Exclusion Criteria:

* Pregnant or breastfeeding.
* Received prior radiotherapy on the bladder tumor.
* Received a partial cystectomy.
* Any prior systemic anti-cancer therapy including investigational agents and immunotherapy.
* Following cardio-vascular risk factors:

  1. Myocardial infarction in the past 6 months before planned treatment start.
  2. Uncontrolled heart failure.
  3. Uncontrolled ventricular arrhythmia.
  4. A peri/myocarditis in the past 3 months before planned treatment start. Note: Stable atrial fibrillation is permissive with or without anticoagulation if there was no decompensation in the past 3 months before planned treatment start.
* Left ventricular ejection fraction (LVEF) \< 50% measured by echocardiogram or MUGA.
* QTcF ≥ 470 ms regardless of sex.
* Any active autoimmune disease requiring systemic immunosuppressive treatments.
* Any history of non-infectious pneumonitis \< 6 months prior to Screening.
* Any active inflammatory bowel disease such as Crohn's disease or ulcerative colitis which are generally excluded or active autoimmune thyroiditis present \< 6 months prior to Screening.
* History of CNS disease such as stroke, seizure, encephalitis, or multiple sclerosis (\< 6 months prior to Screening).