Clinical trial NCT06059547: Neoadjuvant Immunotherapy Combined With the Anti-GDF-15 Antibody Visugromab to Treat Muscle Invasive Bladder Cancer
Official title: A Multi-center Phase 2 Study of Neoadjuvant Immunotherapy in Combination With the Anti-GDF-15 Antibody Visugromab (CTL-002) for the Treatment of Muscle Invasive Bladder
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Bladder Cancer
Adult Solid Tumor
Keywords: CTL-002
visugromab
GDF-15
Lead sponsor: CatalYm GmbH
Sponsor class: INDUSTRY
First posted: 2023-09-28
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Subjects will be assigned to a treatment group based on tumor tissue and tumor size.
Primary purpose: TREATMENT

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.


Eligibility 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.
* 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).

Primary outcomes:
measure: Pathologic complete response rate
timeFrame: min. 4 months
measure: Radiologic response rate according RECIST
timeFrame: min. 4 months
Secondary outcomes:
measure: Adverse Events
timeFrame: min. 6 months
measure: Treatment related delay of surgery
timeFrame: min. 4 months
measure: Cmax following the first dose of Visugromab (CTL-002)
timeFrame: 1 day
measure: AUC following the first dose of Visugromab (CTL-002)
timeFrame: 28 days
measure: Half-life of Visugromab (CTL-002)
timeFrame: min. 3 months
measure: GDF-15 serum levels
timeFrame: 1 day
measure: Evaluation of tumor stage downgrading from baseline to Radical Cystectomy/Re-TURBT
timeFrame: min. 3 months
measure: Evaluation of EFS (Event-free Survival)
timeFrame: 12 months after Radical Cystectomy/Re-TURBT
measure: OS (Overall Survival)
timeFrame: 15 months
measure: Evaluation of TTR (Time to Relapse)
timeFrame: 12 months after Radical Cystectomy/Re-TURBT
measure: isugromab-induced anti-drug antibodies (ADA) development.
timeFrame: min. 5 months
Other outcomes:
measure: Tumor biopsy analysis
timeFrame: min. 3 months
measure: Evaluation of selected cytokine and chemokine concentration in peripheral blood
timeFrame: min. 3 months
Locations:
city: Milano
country: Italy
facility: IRCCS Ospedale San Raffaele Hospital Vita-Salute San Raffaele University
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori IRCCS - Fondazione Pascale
city: Padova
country: Italy
facility: Istituto Oncologico Veneto, IOV - IRCCS
city: Pagani
country: Italy
facility: ASL Salerno, Ospedale Andrea Tortora
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS, UOC Oncologia Medica
city: Torino
country: Italy
facility: A.O.U. Città della Salute e della Scienza di Torino
city: Torino
country: Italy
facility: Azienda Ospedaliera Ordine Mauriziano di Torino Ospedale Umberto I , SCDU Oncologia
Study officials:
affiliation: CatalYm GmbH
name: Felix Lichtenegger, MD
role: STUDY_DIRECTOR
References: