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

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ClinicalTrials.gov Identifier: NCT06059547
Recruitment Status : Recruiting
First Posted : September 28, 2023
Last Update Posted : September 28, 2023
Sponsor:
Information provided by (Responsible Party):
CatalYm GmbH

Study Description
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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) who cannot receive or refuse to receive cisplatin-based chemotherapy.

Condition or disease Intervention/treatment Phase
Bladder Cancer Adult Solid Tumor Drug: Nivolumab Drug: Visugromab (CTL-002) Drug: Placebo Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Subjects will be assigned to a treatment group based on tumor tissue and tumor size.
Masking: Single (Participant)
Primary Purpose: Treatment
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
Actual Study Start Date : September 6, 2023
Estimated Primary Completion Date : August 31, 2024
Estimated Study Completion Date : August 31, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bladder Cancer
Drug Information available for: Nivolumab

Arms and Interventions
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Arm Intervention/treatment
Active Comparator: Combination with Placebo
Placebo + Checkpoint Inhibitor nivolumab
 Drug: Nivolumab
Biological, monoclonal antibody

Drug: Placebo
Placebo 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


Outcome Measures
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Primary Outcome Measures :
  1. Pathologic complete response rate [ Time Frame: min. 3 months ]
    Rate of subjects with no viable tumor cells in Radical Cystectomy Resection

  2. Radiologic response rate according RECIST [ Time Frame: min. 3 months ]
    RECIST 1.1 prior Radical Cystectomy


Secondary Outcome Measures :
  1. Adverse Events [ Time Frame: min. 4 months ]
    Incidence of treatment emergent adverse events

  2. Treatment related delay of surgery [ Time Frame: min. 4 months ]
    Treatment related delay of Radical Cystectomy > 8 weeks after last dose of study

  3. Cmax following the first dose of Visugromab (CTL-002) [ Time Frame: 1 day ]
    PK parameter from serum Visugromab (CTL-002) levels

  4. AUC following the first dose of Visugromab (CTL-002) [ Time Frame: 14 days ]
    PK parameter from serum Visugromab (CTL-002) levels

  5. Half-life of Visugromab (CTL-002) [ Time Frame: min. 3 months ]
    PK parameter from serum Visugromab (CTL-002) levels

  6. GDF-15 serum levels [ Time Frame: 1 day ]
    Measurement of concentration in peripheral blood

  7. Evaluation of tumor stage downgrading from baseline to Radical Cystectomy [ Time Frame: min. 3 months ]
  8. Evaluation of EFS (Event-free Survival) [ Time Frame: 12 months after Radical Cystectomy ]

    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.


  9. OS (Overall Survival) [ Time Frame: 15 months ]

    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.



Other Outcome Measures:
  1. Evaluation of immune cell abundance by density (positive cells/mm2 of tumor) in tumor tissue [ Time Frame: min. 3 months ]
  2. Evaluation of selected cytokine concentration in peripheral blood [ Time Frame: min. 3 months ]
  3. Evaluation of selected chemokine concentration in peripheral blood [ Time Frame: min. 3 months ]
  4. Assessment of molecular profile [ Time Frame: min. 3 months ]

    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


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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).
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06059547


Contacts
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Contact: Frank Hermann, MD +49 89 200066440 frank.hermann@catalym.com
Contact: Petra Fettes, PhD +49 89 200066440 petra.fettes@catalym.com

Locations
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Italy
IRCCS Ospedale San Raffaele Hospital Vita-Salute San Raffaele University Recruiting
Milano, Italy, 20132
Contact: Andrea Necchi, Prof. Dr.         
Fondazione Policlinico Universitario Agostino Gemelli IRCCS, UOC Oncologia Medica Recruiting
Roma, Italy, 00168
Contact: Roberto Iacovelli, Dr.         
A.O.U. Città della Salute e della Scienza di Torino Not yet recruiting
Torino, Italy, 10126
Contact: Paolo Gontenero, Prof. Dr.         
Azienda Ospedaliera Ordine Mauriziano di Torino Ospedale Umberto I , SCDU Oncologia Not yet recruiting
Torino, Italy, 10128
Contact: Massimo Di Maio, Prof. Dr.         
Sponsors and Collaborators
CatalYm GmbH
Investigators
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Study Director: Frank Hermann, MD CatalYm GmbH
More Information
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Responsible Party: CatalYm GmbH
ClinicalTrials.gov Identifier: NCT06059547    
Other Study ID Numbers: CTL-002-002
First Posted: September 28, 2023    Key Record Dates
Last Update Posted: September 28, 2023
Last Verified: September 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by CatalYm GmbH:
CTL-002
visugromab
GDF-15
Additional relevant MeSH terms:
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Urinary Bladder Neoplasms
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
Nivolumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action