Neoadjuvant Immunotherapy Combined With the Anti-GDF-15 Antibody Visugromab to Treat Muscle Invasive Bladder Cancer
- Conditions
- Bladder CancerAdult Solid Tumor
- Interventions
- Registration Number
- NCT06059547
- Lead Sponsor
- CatalYm GmbH
- Brief Summary
This is a multi-center, stratified and single-blinded Phase 2 study of neoadjuvant immunotherapy in combination with the antiGDF15 antibody visugromab (CTL-002) for the treatment of subjects with MIBC set to undergo radical Cystectomy (RC)/Re-TURBT who cannot receive or refuse to receive cisplatin-based chemotherapy.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 30
- 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
- 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.
- Pre-existing arrhythmia, uncontrolled angina pectoris, uncontrolled heart failure (NYHA) Grade IV, any myocardial infarction/coronary event, CNS-ischemic event and any thromboembolic event at any time < 6 months prior to Screening or presence of uncontrolled heart failure NYHA Grade III or higher.
- Left ventricular ejection fraction (LVEF) < 50% measured by echocardiogram or MUGA.
- QTcF ≥ 470 ms regardless of sex.
- Any active autoimmune 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 autoimmunthyroiditis present < 6 months prior to Screening.
- History of CNS disease such as stroke, seizure, encephalitis, or multiple sclerosis (< 6 months prior to Screening).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Combination with Visugromab/Verum Visugromab (CTL-002) visugromab (CTL-002) + Checkpoint Inhibitor nivolumab Combination with Placebo Placebo Placebo + Checkpoint Inhibitor nivolumab Combination with Placebo Nivolumab Placebo + Checkpoint Inhibitor nivolumab Combination with Visugromab/Verum Nivolumab visugromab (CTL-002) + Checkpoint Inhibitor nivolumab
- Primary Outcome Measures
Name Time Method Pathologic complete response rate min. 4 months Rate of subjects with no viable tumor cells in Radical Cystectomy Resection/Re-TURBT
Radiologic response rate according RECIST min. 4 months RECIST 1.1 prior Radical Cystectomy/Re-TURBT
- Secondary Outcome Measures
Name Time Method Cmax following the first dose of Visugromab (CTL-002) 1 day PK parameter from serum Visugromab (CTL-002) levels
Evaluation of EFS (Event-free Survival) 12 months after Radical Cystectomy/Re-TURBT Event-free survival will be defined as the time from first study drug administration to one of the following:
Radiographic disease progression precluding a curative intent surgery per RECIST v1.1 prior to RC/Re-TURBT
Initiation of neoadjuvant chemotherapy preceding RC/Re.TURBT as per Investigator decision
Inability to undergo RC/Re-TURBT due to the onset of treatment-related side effects
Inability to complete a curative intent surgery determined by the urologist at the time of RC/Re-TURBT (e.g., unresectable tumor, metastases discovered at RC)
Local or distant recurrence assessed by cross-sectional imaging and/or biopsy after RC/Re-TURBT
Death from any cause. In this study, subject refusal to undergo RC due to the evidence of complete or near-complete clinical response (assessed on cross-sectional imaging as previously described) will not be considered an event.isugromab-induced anti-drug antibodies (ADA) development. min. 5 months The number and percentage of subjects with any detectable ADA after first IMP administration
Adverse Events min. 6 months Incidence of treatment emergent adverse events
Treatment related delay of surgery min. 4 months Treatment related delay of Radical Cystectomy/Re-TURBT \> 8 weeks after last dose of study
AUC following the first dose of Visugromab (CTL-002) 28 days PK parameter from serum Visugromab (CTL-002) levels
GDF-15 serum levels 1 day Measurement of concentration in peripheral blood
Evaluation of tumor stage downgrading from baseline to Radical Cystectomy/Re-TURBT min. 3 months Pathological response evaluation according to American Joint Committee on Cancer Staging System, 8th edition, 2017
OS (Overall Survival) 15 months Overall survival is defined as the time from the first study drug administration to the date of death, regardless of the cause of death.
Subjects who were alive at the time of the analysis will be censored at the date the subject was last known to be alive.Evaluation of TTR (Time to Relapse) 12 months after Radical Cystectomy/Re-TURBT Time to relapse will be measured from the time of RC/Re-TURBT until the day of documented relapse.
Half-life of Visugromab (CTL-002) min. 3 months PK parameter from serum Visugromab (CTL-002) levels
Trial Locations
- Locations (8)
IRCCS Ospedale San Raffaele Hospital Vita-Salute San Raffaele University
🇮🇹Milano, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹Milano, Italy
Istituto Nazionale Tumori IRCCS - Fondazione Pascale
🇮🇹Napoli, Italy
Istituto Oncologico Veneto, IOV - IRCCS
🇮🇹Padova, Italy
ASL Salerno, Ospedale Andrea Tortora
🇮🇹Pagani, Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS, UOC Oncologia Medica
🇮🇹Roma, Italy
A.O.U. Città della Salute e della Scienza di Torino
🇮🇹Torino, Italy
Azienda Ospedaliera Ordine Mauriziano di Torino Ospedale Umberto I , SCDU Oncologia
🇮🇹Torino, Italy