Neoadjuvant Immunotherapy in Combination With the Anti-GDF-15 Antibody Visugromab (CTL-002) for Treatment of Muscle Invasive Bladder Cancer

Bladder Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06059547
• Other study ID #: CTL-002-002
• Status: Recruiting
• Phase: Phase 2
• Start date: September 6, 2023
• Est. completion date: August 31, 2025

Study information

• Verified date: September 2023
• Source: CatalYm GmbH
• Contact: Frank Hermann, MD
• Phone: +49 89 200066440
• Email: frank.hermann[@]catalym.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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) who cannot receive or refuse to receive cisplatin-based chemotherapy.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: August 31, 2025
• Est. primary completion date: August 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 for bladder cancer.
• 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 > 450 ms for men or > 470 ms for women.
• 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).

Related Conditions & MeSH terms

• Adult Solid Tumor
• Bladder Cancer
• Urinary Bladder Neoplasms

Intervention

Drug:
• Nivolumab
Biological, monoclonal antibody
• Visugromab (CTL-002)
Biological, monoclonal antibody
• Placebo
Placebo for Visugromab (CTL-002)

Locations

Country	Name	City	State
Italy	IRCCS Ospedale San Raffaele Hospital Vita-Salute San Raffaele University	Milano
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

Sponsors (1)

Lead Sponsor	Collaborator
CatalYm GmbH

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Evaluation of immune cell abundance by density (positive cells/mm2 of tumor) in tumor tissue		min. 3 months
Other	Evaluation of selected cytokine concentration in peripheral blood		min. 3 months
Other	Evaluation of selected chemokine concentration in peripheral blood		min. 3 months
Other	Assessment of molecular profile	Examples: Analysis of tumor mutational burden (TMB) defined as the number of somatic mutations per megabase of interrogated genomic sequences.; Analysis of differential gene expression as fold change of target gene expression in a target sample relative to a reference sample, normalized to a reference gene	min. 3 months
Primary	Pathologic complete response rate	Rate of subjects with no viable tumor cells in Radical Cystectomy Resection	min. 3 months
Primary	Radiologic response rate according RECIST	RECIST 1.1 prior Radical Cystectomy	min. 3 months
Secondary	Adverse Events	Incidence of treatment emergent adverse events	min. 4 months
Secondary	Treatment related delay of surgery	Treatment related delay of Radical Cystectomy > 8 weeks after last dose of study	min. 4 months
Secondary	Cmax following the first dose of Visugromab (CTL-002)	PK parameter from serum Visugromab (CTL-002) levels	1 day
Secondary	AUC following the first dose of Visugromab (CTL-002)	PK parameter from serum Visugromab (CTL-002) levels	14 days
Secondary	Half-life of Visugromab (CTL-002)	PK parameter from serum Visugromab (CTL-002) levels	min. 3 months
Secondary	GDF-15 serum levels	Measurement of concentration in peripheral blood	1 day
Secondary	Evaluation of tumor stage downgrading from baseline to Radical Cystectomy		min. 3 months
Secondary	Evaluation of EFS (Event-free Survival)	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; Initiation of neoadjuvant chemotherapy preceding RC as per Investigator decision; Inability to undergo RC 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 (e.g., unresectable tumor, metastases discovered at RC); Local or distant recurrence assessed by cross-sectional imaging and/or biopsy after RC; 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.	12 months after Radical Cystectomy
Secondary	OS (Overall Survival)	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.	15 months