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

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 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.

Study Overview

• Status: Active, not recruiting
• Conditions: Adult Solid Tumor; Bladder Cancer
• Intervention / Treatment: Drug: Nivolumab; Drug: Visugromab (CTL-002); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Milan, Italy, 20133
    • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Milan, Italy, 20132
    • IRCCS Ospedale San Raffaele Hospital Vita-Salute San Raffaele University
  • Roma, Italy, 00168
    • Fondazione Policlinico Universitario Agostino Gemelli IRCCS, UOC Oncologia Medica
  • Torino, Italy, 10126
    • A.O.U. Città della Salute e Della Scienza di Torino

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Combination with Placebo; Placebo + Checkpoint Inhibitor nivolumab	Drug: Nivolumab; Biological, monoclonal antibody; Drug: Placebo; Placebo (NaCl) for Visugromab (CTL-002)
Experimental: Combination with Visugromab/Verum; visugromab (CTL-002) + Checkpoint Inhibitor nivolumab	Drug: Nivolumab; Biological, monoclonal antibody; Drug: Visugromab (CTL-002); Biological, monoclonal antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological complete response rate	Rate of participants with complete pathological responses after IMP treatment as determined by local pathologist review	min. 4 months
Radiological response rate according RECIST	Rate of participants with radiological responses according to RECIST 1.1 prior Radical Cystectomy/Re-TURBT as assessed by the Investigator/Radiologist	min. 4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax following the first dose of Visugromab (CTL-002)	PK parameter from serum Visugromab (CTL-002) levels	1 day
Half-life of Visugromab (CTL-002)	PK parameter from serum Visugromab (CTL-002) levels	min. 3 months
GDF-15 serum levels	Measurement of concentration in peripheral blood	1 day
AUC following the first dose of Visugromab (CTL-002)	PK parameter from serum Visugromab (CTL-002) levels	28 days
Evaluation of TTR (Time to Relapse)	Time to relapse will be measured from the time of RC/Re-TURBT until the day of documented relapse.	12 months after Radical Cystectomy/Re-TURBT
Adverse Events	Incidence of adverse events (related or unrelated to IMPs)	min. 6 months
Treatment related delay of surgery	Treatment related delay of Radical Cystectomy/Re-TURBT > 8 weeks after last dose of IMP	min. 6 months
Pathological complete response rate	Rate of participants with complete pathological responses after IMP treatment as determined by central independent pathological review	min. 4 months
Radiological response rate according RECIST	Rate of participants with radiological responses according to RECIST 1.1 prior Radical Cystectomy/Re-TURBT as assessed by the central independent review	Min. 4 months
Major pathological response rate	Rate of participants with major pathological responses after IMP treatment as determined by local pathologist review or central independent pathological review	Min. 4 months
Evaluation of EFS (Event-free Survival)	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.	12 months after Radical Cystectomy/Re-TURBT
OS (Overall Survival)	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.	15 months
Visugromab-induced anti-drug antibodies (ADA) development.	The number and percentage of participants with any detectable ADA after first IMP administration	min. 5 months

Other Outcome Measures

Outcome Measure	Time Frame
Tumor biopsy analysis	min. 3 months
Evaluation of selected cytokine and chemokine concentration in peripheral blood	min. 3 months

Collaborators and Investigators

• Sponsor: CatalYm GmbH
• Investigators: Study Director: Felix Lichtenegger, MD, CatalYm GmbH

Study record dates

Study Major Dates

• Study Start (Actual): September 6, 2023
• Primary Completion (Actual): October 16, 2025
• Study Completion (Estimated): October 16, 2026

Study Registration Dates

• First Submitted: August 23, 2023
• First Submitted That Met QC Criteria: September 21, 2023
• First Posted (Actual): September 28, 2023

Study Record Updates

• Last Update Posted (Actual): December 11, 2025
• Last Update Submitted That Met QC Criteria: December 5, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: CTL-002; GDF-15; visugromab
• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urologic Neoplasms; Urinary Bladder Diseases; Urinary Bladder Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Nivolumab
• Other Study ID Numbers: CTL-002-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No