Assessment of Safety, Tolerability, Radiation Dosimetry, Imaging Properties of 89Zr-girentuximab in Patients With NMIBC

A Pilot Open-label, Feasibility Study to Assess safEty, Tolerability, Radiation Dosimetry, and Imaging Properties of 89Zr-labeled giRenTuximab (89Zr-Girentuximab) in patIents With Non-musclE-iNvasive Bladder CancEr (NMIBC)

The purpose of this study is to evaluate the use of 89Zr-labeled girentuximab (89Zr-TLX250) as a novel, carbonic anhydrase IX (CAIX) targeted PET/CT radiopharmaceutical for the imaging of Non-muscle-invasive bladder cancer (NMIBC) patients.

There is a real need for treatment of NMIBC. Currently, treatment options include Bacillus Calmette-Guerin (BCG) intravesical immunotherapy and mitomycin C chemotherapy. These therapies are efficient for some time but relapses repeat them at more and more close intervals and finally patients are refractory to them and require a radical cystectomy.

CAIX is expressed in 70% to 90% of bladder cancers but not in normal urothelial tissue. CAIX is expressed on the membrane of Non-Muscle-Invasive Bladder Cancer cells.

Girentuximab, an anti-CAIX antibody could be a promising target in NMIBC. PET/CT with Girentuximab labelled with 89Zirconium will be used for diagnosis purpose. 89Zr-Girentuximab will be administered by intravesical instillation.

In this study, patients with Non-Muscle-Invasive Bladder Cancer (NMIBC) will be enrolled in this study after confirmation of their eligibility.

A single intravesical administration of 89Zr-Girentuximab will be performed at day 0.

Multiple PET/CT imaging sessions will be performed on day 0, day 1 and day 2 in order to evaluate the bladder and the whole body 89Zr girentuximab uptake.

Inclusion Criteria:

• Written informed consent obtained from the patient prior to performing any protocol-related procedures, including screening evaluations.
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
• Female or male, Age ≥ 18 years at time of study entry.
• Performance Status: 0 or 1.
• Clinical evidence of NMIBC based on cystoscopy and proven histologically of papillary tumors.
• Histologically-confirmed pTa Grade 3 or pT1 Grade 3 bladder cancer patients relapsing without muscle invasion.
• Negative sterile Urine cytobacteriological testing at baseline (T0).
• Consent to use a contraception method for at least 30 days after administration of 89Zr-girentuximab.
• Patient has valid health insurance.

Exclusion Criteria:

• Patient with urinary incontinence.
• Known hypersensitivity to girentuximab.
• Exposure to any experimental diagnostic or therapeutic drug within 30 days prior the date of planned administration of 89Zr-girentuximab
• Exposure to any radiopharmaceutical within 30 days (corresponding to 10 half-lives of Zr-89) prior to the administration of 89Zr-girentuximab
• Patients suffering from a bladder cancer at stage pT2, pT3 or pT4
• Serious non-malignant disease that may interfere with the objectives of the study or with the safety or compliance of the patient; as judged by the investigator
• Concomitant cancer in the past 5 years except cutaneous cancers (except melanoma) and in situ carcinoma
• Prior chemotherapy, radiotherapy (other than short cycle of palliative radiotherapy), immunotherapy within 21 days of 89Zr-girentuximab administration
• Patients with known human immunodeficiency viruses (HIV), Hepatitis B virus (HBV) and Hepatitis C Virus (HCV) infections,
• Pregnant or likely to be pregnant or nursing patient.
• Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study
• Persons deprived of their liberty, under a measure of safeguard of justice, under guardianship or placed under the authority of a guardian.