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

Phase 1Not Yet RecruitingNCT07260162

Institut Cancerologie de l'Ouest24 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Bladder Cancer

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

To determine the Maximum Tolerated Dose (MTD) of ATO-101™.

The primary endpoint is the occurrence of dose-limiting toxicities (DLTs) during the DLT observation period.

Time frame: 15 days

To determine the Recommended Dose for Expansion (RDE) of ATO-101™.