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

NCT06059547 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: CTL-002-002
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 4

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.

Conditions

Adult Solid Tumor; Bladder Cancer

Keywords

CTL-002; visugromab; GDF-15

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (13)

• Adverse Events

  min. 6 months

• Treatment related delay of surgery

  min. 6 months

• Cmax following the first dose of Visugromab (CTL-002)

  1 day

• AUC following the first dose of Visugromab (CTL-002)

  28 days

• Half-life of Visugromab (CTL-002)

  min. 3 months

Other Outcomes (2)

• Tumor biopsy analysis

  min. 3 months

• Evaluation of selected cytokine and chemokine concentration in peripheral blood

  min. 3 months

Study Arms (2)

Combination with Placebo

ACTIVE COMPARATOR

Placebo + Checkpoint Inhibitor nivolumab

Drug: Nivolumab; Drug: Placebo

Combination with Visugromab/Verum

EXPERIMENTAL

visugromab (CTL-002) + Checkpoint Inhibitor nivolumab

Drug: Nivolumab; Drug: Visugromab (CTL-002)

Interventions

Nivolumab DRUG

Biological, monoclonal antibody

Combination with Placebo; Combination with Visugromab/Verum

Placebo DRUG

Placebo (NaCl) for Visugromab (CTL-002)

Combination with Placebo

Visugromab (CTL-002) DRUG

Biological, monoclonal antibody

Combination with Visugromab/Verum

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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:
• Myocardial infarction in the past 6 months before planned treatment start.
• Uncontrolled heart failure.
• Uncontrolled ventricular arrhythmia.
• 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).

Sponsors & Collaborators

• CatalYm GmbH: lead

Study Sites (4)

IRCCS Ospedale San Raffaele Hospital Vita-Salute San Raffaele University

Milan, 20132, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli IRCCS, UOC Oncologia Medica

Roma, 00168, Italy

Location

A.O.U. Città della Salute e della Scienza di Torino

Torino, 10126, Italy

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Felix Lichtenegger, MD

  CatalYm GmbH

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 23, 2023
• First Posted: September 28, 2023
• Study Start: September 6, 2023
• Primary Completion: October 16, 2025
• Study Completion (Estimated): October 16, 2026
• Last Updated: December 11, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

IT (4)