Adult Solid Tumor, Bladder Cancer
Conditions
Keywords
CTL-002, visugromab, GDF-15
Brief summary
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.
Interventions
DRUGNivolumab
Biological, monoclonal antibody
Biological, monoclonal antibody
DRUGPlacebo
Placebo (NaCl) for Visugromab (CTL-002)
Sponsors
CatalYm GmbH
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Intervention model description
Participants will be stratified into four cohorts based on disease stage and PD-L1 expression. Within each cohort, participants are centrally and sequentially assigned to one of two treatment arms in a non-randomized, parallel assignment model.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathological complete response rate | min. 4 months | Rate of participants with complete pathological responses after IMP treatment as determined by local pathologist review |
| Radiological response rate according RECIST | min. 4 months | Rate of participants with radiological responses according to RECIST 1.1 prior Radical Cystectomy/Re-TURBT as assessed by the Investigator/Radiologist |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Major pathological response rate | Min. 4 months | Rate of participants with major pathological responses after IMP treatment as determined by local pathologist review or central independent pathological review |
| Adverse Events | min. 6 months | Incidence of adverse events (related or unrelated to IMPs) |
| Treatment related delay of surgery | min. 6 months | Treatment related delay of Radical Cystectomy/Re-TURBT \> 8 weeks after last dose of IMP |
| Cmax following the first dose of Visugromab (CTL-002) | 1 day | PK parameter from serum Visugromab (CTL-002) levels |
| AUC following the first dose of Visugromab (CTL-002) | 28 days | PK parameter from serum Visugromab (CTL-002) levels |
| Half-life of Visugromab (CTL-002) | min. 3 months | PK parameter from serum Visugromab (CTL-002) levels |
| GDF-15 serum levels | 1 day | Measurement of concentration in peripheral blood |
| Evaluation of EFS (Event-free Survival) | 12 months after Radical Cystectomy/Re-TURBT | Event-free survival will be defined as the time from first IMP 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 trial, participant 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. |
| OS (Overall Survival) | 15 months | Overall survival is defined as the time from the first IMP administration to the date of death, regardless of the cause of death. Participants who were alive at the time of the analysis will be censored at the date the participant 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. |
| Pathological complete response rate | min. 4 months | Rate of participants with complete pathological responses after IMP treatment as determined by central independent pathological review |
| Visugromab-induced anti-drug antibodies (ADA) development. | min. 5 months | The number and percentage of participants with any detectable ADA after first IMP administration |
| Radiological response rate according RECIST | Min. 4 months | Rate of participants with radiological responses according to RECIST 1.1 prior Radical Cystectomy/Re-TURBT as assessed by the central independent review |
Countries
Italy
Contacts
STUDY_DIRECTORFelix Lichtenegger, MD
CatalYm GmbH
Outcome results
None listed