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

Phase 2Active Not RecruitingNCT06059547

CatalYm GmbH31 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

Conditions

Bladder Cancer Adult Solid Tumor

Interventions

NivolumabDRUG

Biological, monoclonal antibody

Visugromab (CTL-002)DRUG

Biological, monoclonal antibody

PlaceboDRUG

Placebo (NaCl) for Visugromab (CTL-002)

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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. * 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).

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

Outcomes

Primary Outcomes

Pathological complete response rate

Rate of participants with complete pathological responses after IMP treatment as determined by local pathologist review

Time frame: 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

Time frame: min. 4 months

Secondary Outcomes

Adverse Events

Incidence of adverse events (related or unrelated to IMPs)

Time frame: min. 6 months

Treatment related delay of surgery

Treatment related delay of Radical Cystectomy/Re-TURBT \> 8 weeks after last dose of IMP

Time frame: min. 6 months

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

PK parameter from serum Visugromab (CTL-002) levels

Time frame: 1 day

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

PK parameter from serum Visugromab (CTL-002) levels

Time frame: 28 days

Half-life of Visugromab (CTL-002)

PK parameter from serum Visugromab (CTL-002) levels

Time frame: min. 3 months

GDF-15 serum levels

Measurement of concentration in peripheral blood

Time frame: 1 day

Data from ClinicalTrials.gov

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