Non-Muscle-Invasive Bladder cancer (NMIBC) tumours often recur despite TransUrethral Resection of Bladder (TURB) and Bacillus Calmette-Guerin (BCG) intravesical instillations, and have no effective conservative treatment options. Alpha emitters like Astatine-211 (211At), due to their short path and short half-life, show promise for superficial targets such as NMIBC.

Carbonic anhydrase IX (CAIX), overexpressed in 70-90% of NMIBC cases but absent in healthy tissues, is an ideal target.

A clinical feasibility Positron emission tomography-computed tomography (PET/CT) imaging study (Pertinence, NCT04897763) was conducted at Institut de cancérologie Ouest (ICO) in six patients using Girentuximab labelled with Zirconium-89 ([89Zr]Zr-girentuximab). It demonstrated successful tracer targeting and no radioactive leakage beyond the bladder following intravesical instillation. The study also confirmed the absence of toxicity, contamination, or significant additional staff radiation exposure.

ATO-101™ ([²¹¹At]At-girentuximab) could enable localised tumour destruction while preserving the bladder in patients with BCG-unresponsive NMIBC. The ongoing First In Human (FIH) study evaluate the safety of ATO-101™ in patients with BCG-unresponsive NMIBC.

Inclusion Criteria:

• Performance Status (PS): 0 or 1.
• Patient experiencing relapse following standard treatment (BCG therapy with or without Mitomycin), before radical surgery which is being considered as a therapeutic option.
• Clinical evidence of NMIBC based on cystoscopy and proven histologically of papillary tumours.
• Histologically confirmed bladder cancer patients relapsing without muscle invasion.
• Negative serum/urine pregnancy test prior to ATO-101™ administration for female patient of childbearing potential.
• Consent to use a contraception method for at least 3 months after administration of ATO-101™.
• Adequate organ function confirmed by laboratory tests results allowing for safe administration of ATO-101™.

Exclusion Criteria:

• Patient with urinary incontinence.
• Patient treated with anticoagulant or platelet antiaggregant therapies.
• Symptoms of urine infection.
• Patient with urethral stenosis.
• Patient with valvular heart disease.
• No history of congestive heart failure.
• Known hypersensitivity to Girentuximab.
• Exposure to any experimental diagnostic or therapeutic drug within 30 days prior the date of planned administration of ATO-101™.
• 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 in past 3 years.
• Prior chemotherapy, radiotherapy (other than short cycle of palliative radiotherapy), immunotherapy within 21 days of ATO-101™ administration.
• Pregnant or likely to be pregnant or nursing patient.