Evaluation of Safety, Tolerability and Response of ATO-101™ in Patients With Non-Muscle-Invasive Bladder Cancer (PERSEVERANCE EU)

Institut Cancerologie de l'Ouest

Status and phase

Not yet enrolling

Phase 1

Conditions

Bladder Cancer

Treatments

Drug: ATO-101™

Study type

Interventional

Funder types

Other

Identifiers

NCT07260162

ICO-2023-18

Details and patient eligibility

About

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.

Enrollment

24 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.