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

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.

Study Overview

• Status: Recruiting
• Conditions: Adult Solid Tumor; Bladder Cancer
• Intervention / Treatment: Drug: Nivolumab; Drug: Placebo; Drug: Visugromab (CTL-002)

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Petra Fettes, PhD; Phone Number: +49 89 200066440; Email: petra.fettes@catalym.com
• Study Contact Backup: Name: Frank Hermann, MD; Phone Number: +49 89 200066440; Email: frank.hermann@catalym.com

Study Locations

• Italy
  • Milano, Italy, 20132
    • Recruiting
    • IRCCS Ospedale San Raffaele Hospital Vita-Salute San Raffaele University
    • Contact: Andrea Necchi, Prof. Dr.
  • Roma, Italy, 00168
    • Recruiting
    • Fondazione Policlinico Universitario Agostino Gemelli IRCCS, UOC Oncologia Medica
    • Contact: Roberto Iacovelli, Dr.
  • Torino, Italy, 10126
    • Not yet recruiting
    • A.O.U. Città della Salute e della Scienza di Torino
    • Contact: Paolo Gontenero, Prof. Dr.
  • Torino, Italy, 10128
    • Not yet recruiting
    • Azienda Ospedaliera Ordine Mauriziano di Torino Ospedale Umberto I , SCDU Oncologia
    • Contact: Massimo Di Maio, Prof. Dr.

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 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).

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Incidence of treatment emergent adverse events	min. 4 months
Treatment related delay of surgery	Treatment related delay of Radical Cystectomy > 8 weeks after last dose of study	min. 4 months
Cmax following the first dose of Visugromab (CTL-002)	PK parameter from serum Visugromab (CTL-002) levels	1 day
AUC following the first dose of Visugromab (CTL-002)	PK parameter from serum Visugromab (CTL-002) levels	14 days
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
Evaluation of tumor stage downgrading from baseline to Radical Cystectomy		min. 3 months
Evaluation of EFS (Event-free Survival)	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.	12 months after Radical Cystectomy
OS (Overall Survival)	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.	15 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of immune cell abundance by density (positive cells/mm2 of tumor) in tumor tissue		min. 3 months
Evaluation of selected cytokine concentration in peripheral blood		min. 3 months
Evaluation of selected chemokine concentration in peripheral blood		min. 3 months
Assessment of molecular profile	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	min. 3 months

Collaborators and Investigators

• Sponsor: CatalYm GmbH
• Investigators: Study Director: Frank Hermann, MD, CatalYm GmbH

Study record dates

Study Major Dates

• Study Start (Actual): September 6, 2023
• Primary Completion (Estimated): August 31, 2024
• Study Completion (Estimated): August 31, 2025

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): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 21, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: CTL-002; GDF-15; visugromab
• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urinary Bladder Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; 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: No
• Studies a U.S. FDA-regulated device product: No