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

This is a multi-center, stratified and single-blinded Phase 2 trial of neoadjuvant immunotherapy in combination with the anti-GDF15 antibody visugromab (CTL-002) for the treatment of participants with MIBC set to undergo radical Cystectomy (RC)/Re-TURBT who cannot receive or refuse to receive cisplatin-based chemotherapy.

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).