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

Phase 2

Active, not recruiting

• Conditions: Muscle invasive bladder cancer set to undergo radical cystectomy who cannot receive or refuse to receive cisplatin-based chemotherapy

• Registration Number: 2024-513957-55-00
• Lead Sponsor: CatalYm GmbH

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-08-23
• Study Start: 2023-09-06
• Study First Submitted QC: 2023-09-21
• Study First Posted: 2023-09-28
• Status Verified: 2025-08
• Last Update Submitted: 2025-08-25
• Primary Completion: 2025-08-30
• Last Update Posted: 2025-09-02
• Study Completion: 2026-09-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 31

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
Pathological complete response rate	min. 4 months	Rate of participants with complete pathological responses after IMP treatment as determined by central independent pathological 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 central independent review
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
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.
Visugromab-induced anti-drug antibodies (ADA) development.	min. 5 months	The number and percentage of participants with any detectable ADA after first IMP administration

Trial Locations

Locations (4)

IRCCS Ospedale San Raffaele Hospital Vita-Salute San Raffaele University; 🇮🇹 Milan, Italy

Fondazione IRCCS Istituto Nazionale dei Tumori; 🇮🇹 Milan, 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