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

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

Tracking Information

• First Submitted Date: August 23, 2023
• First Posted Date: September 28, 2023
• Last Update Posted Date: September 28, 2023
• Actual Study Start Date: September 6, 2023
• Estimated Primary Completion Date: August 31, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 21, 2023)

• Pathologic complete response rate [ Time Frame: min. 3 months ]
  Rate of subjects with no viable tumor cells in Radical Cystectomy Resection
• Radiologic response rate according RECIST [ Time Frame: min. 3 months ]
  RECIST 1.1 prior Radical Cystectomy

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: September 21, 2023)

• Adverse Events [ Time Frame: min. 4 months ]
  Incidence of treatment emergent adverse events
• Treatment related delay of surgery [ Time Frame: min. 4 months ]
  Treatment related delay of Radical Cystectomy > 8 weeks after last dose of study
• Cmax following the first dose of Visugromab (CTL-002) [ Time Frame: 1 day ]
  PK parameter from serum Visugromab (CTL-002) levels
• AUC following the first dose of Visugromab (CTL-002) [ Time Frame: 14 days ]
  PK parameter from serum Visugromab (CTL-002) levels
• Half-life of Visugromab (CTL-002) [ Time Frame: min. 3 months ]
  PK parameter from serum Visugromab (CTL-002) levels
• GDF-15 serum levels [ Time Frame: 1 day ]
  Measurement of concentration in peripheral blood
• Evaluation of tumor stage downgrading from baseline to Radical Cystectomy [ Time Frame: min. 3 months ]
• 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.
• 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.

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: September 21, 2023)

• Evaluation of immune cell abundance by density (positive cells/mm2 of tumor) in tumor tissue [ Time Frame: min. 3 months ]
• Evaluation of selected cytokine concentration in peripheral blood [ Time Frame: min. 3 months ]
• Evaluation of selected chemokine concentration in peripheral blood [ Time Frame: min. 3 months ]
• 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

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Neoadjuvant Immunotherapy in Combination With the Anti-GDF-15 Antibody Visugromab (CTL-002) for Treatment of Muscle Invasive Bladder Cancer
• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

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

Condition

• Bladder Cancer
• Adult Solid Tumor

Intervention

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

Study Arms

• Active Comparator: Combination with Placebo
  Placebo + Checkpoint Inhibitor nivolumab
  Interventions:

  • Drug: Nivolumab
  • Drug: Placebo
• Experimental: Combination with Visugromab/Verum
  visugromab (CTL-002) + Checkpoint Inhibitor nivolumab
  Interventions:

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 21, 2023): 30
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 31, 2025
• Estimated Primary Completion Date: August 31, 2024 (Final data collection date for primary outcome measure)

Eligibility 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).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Frank Hermann, MD; +49 89 200066440; frank.hermann@catalym.com

Contact: Petra Fettes, PhD; +49 89 200066440; petra.fettes@catalym.com

• Listed Location Countries: Italy

Administrative Information

• NCT Number: NCT06059547
• Other Study ID Numbers: CTL-002-002
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: CatalYm GmbH
• Original Responsible Party: Same as current
• Current Study Sponsor: CatalYm GmbH
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Frank Hermann, MD; CatalYm GmbH

• PRS Account: CatalYm GmbH
• Verification Date: September 2023