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

NCT07260162 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: ICO-2023-18
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Bladder Cancer

Keywords

Non-Muscle-Invasive Bladder cancer (NMIBC); Girentuximab; Astatine 211; Phase I; First In Human (FIH); Carbonic anhydrase IX (CAIX); Intravesical instillation; [211At]At-Girentuximab; ATO-101™

Outcome Measures

Primary Outcomes (2)

• 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.

  15 days

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

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

  15 days

Study Arms (1)

ATO-101™

EXPERIMENTAL

\[211At\]At-Girentuximab (ATO-101™) intravesical administration

Drug: ATO-101™

Interventions

ATO-101™ DRUG

The study drug: \[211At\]At-Girentuximab (ATO-101™) is administered via intravesical instillation

Also known as: [211At]At-Girentuximab

ATO-101™

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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™.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Institut Cancerologie de l'Ouest: lead

Study Sites (1)

Institut de Cancérologie de l'Ouest

Saint-Herblain, Loire Atlantique, 44800, France

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Non-Muscle Invasive Bladder Neoplasms

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Officials

• Caroline ROUSSEAU, MD, PhD

  Institut de Cancérologie de l'OUEST _ ICO

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Caroline ROUSSEAU, MD, PhD

CONTACT

+33 2 40 67 99 00; caroline.rousseau@ico.unicancer.fr

Nadia ALLAM, PhD

CONTACT

+33 2 40 67 99 00; nadia.allam@ico.unicancer.fr

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: ATO-101™ is an anti-CA-IX antibody (Girentuximab) radiolabeled with an alpha-emitting radionuclides (astatine-211)

Study Record Dates

• First Submitted: November 19, 2025
• First Posted: December 3, 2025
• Study Start: February 1, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2028
• Last Updated: December 3, 2025

Record last verified: 2025-11

Locations

FR (1)