Efficacy and Safety of Intravesical TARA-002 Compared With Investigator's Choice of Intravesical Chemotherapy in Participants With BCG-naïve High-grade Non-muscle Invasive Bladder Cancer (ADVANCED-3)

A Phase 3, Randomized Study to Evaluate the Efficacy and Safety of Intravesical TARA-002 Compared With Investigator's Choice of Intravesical Chemotherapy in Participants With BCG-naïve High-Grade Non-Muscle Invasive Bladder Cancer

The goal of this clinical trial is to learn if TARA-002 can treat high-grade non-muscle invasive bladder cancer (NMIBC) in BCG-naïve adults 18 years of age or older.

The main questions it aims to answer are:

• Can the study drug help participants with this type of cancer?
• Is the study drug safe?
• What are the side effects of the study drug?

Researchers will compare TARA-002 to chemotherapy to see if TARA-002 works to treat NMIBC.

Study Overview

• Status: Not yet recruiting
• Conditions: Bladder (Urothelial, Transitional Cell) Cancer; Non-muscle Invasive Bladder Cancer With Carcinoma in Situ; Non-Muscle Invasive Bladder Carcinoma
• Intervention / Treatment: Drug: TARA-002; Drug: Investigator's Choice of Intravesical Chemotherapy

• Study Type: Interventional
• Enrollment (Estimated): 284
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Chief R&D Officer; Phone Number: 16468440337; Email: clinicaltrials@protaratx.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female participants 18 years of age or older at the time of signing informed consent
• Participants who have voluntarily given written informed consent after the nature of the study has been explained according to applicable requirements prior to study entry
• Central histologic confirmation of high-grade non-muscle invasive CIS (± Ta/T1) with active disease
• Participants who are BCG naive, or participants who are BCG exposed and have not received intravesical BCG for at least 24 months prior to the most recent CIS diagnosis, or participants who received ≤2 doses of BCG within the 24 months prior to the most recent CIS diagnosis

Exclusion Criteria:

• Penicillin allergy (participants with a questionable history of allergy to penicillin will undergo penicillin blood allergy testing via central laboratory Central confirmed variant histology
• Concomitant prostatic or upper tract urothelial involvement per Investigator's assessment
• Nodal and metastatic disease are excluded if they existed at any time (whether present or in the past)
• Any history of ≥ T2 bladder cancer that existed at any point in time in the participant's history

For more information on eligibility criteria, please contact the Sponsor.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TARA-002 (Arm A)	Drug: TARA-002; Participants will receive 6 weekly instillations of TARA-002. Participants confirmed to have a CR at Week 12 will enter the maintenance treatment period and will receive 3 additional weekly instillations of TARA-002 every 3 months up to Month 19, and then 3 weekly doses at Month 25. Participants who are eligible for reinduction at Week 12 will receive 6 additional weekly instillations of TARA-002. Participants who undergo reinduction and are confirmed to have a CR at Week 24 will enter the maintenance regimen treatment period and will receive 3 weekly instillations of TARA-002 every 3 months up to Month 19, and then 3 weekly doses at Month 25.
Active Comparator: Investigator's choice of intravesical chemotherapy	Drug: Investigator's Choice of Intravesical Chemotherapy; Participants will receive 6 weekly instillations of Investigator's choice of intravesical chemotherapy. Participants confirmed to have a CR at Week 12 will enter the maintenance regimen treatment period and will receive one intravesical instillation of Investigator's choice of intravesical chemotherapy every 1 month up to Month 25.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of high-grade complete response	Incidence of high-grade complete response of intravesical TARA-002 compared to Investigator's choice of intravesical chemotherapy determined by cystoscopy, urine cytology, and bladder biopsy (if applicable)	Month 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of high-grade complete response	Duration of high-grade complete response of intravesical TARA-002 compared to Investigator's choice of intravesical chemotherapy	Up to Month 60
Treatment emergent adverse events	Incidence and severity of treatment emergent adverse events (TEAEs) of intravesical TARA-002 compared to Investigator's choice of intravesical chemotherapy	Up to Month 60
Treatment emergent serious adverse events	Incidence and severity of treatment emergent serious adverse events (TESAEs) of intravesical TARA-002 compared to Investigator's choice of intravesical chemotherapy	Up to Month 60
High-grade complete response rate	High-grade complete response rate of intravesical TARA-002 compared to Investigator's choice of intravesical chemotherapy determined by cystoscopy, urine cytology, and bladder biopsy (if applicable)	At Months 3, 9, 12, 15, 18, 21, 24, 27, 30, 36, 42, 48, 54, and 60
High-grade complete response rate (CIS only)	High-grade complete response rate of intravesical TARA-002 compared to Investigator's choice of intravesical chemotherapy determined by cystoscopy, urine cytology, and bladder biopsy (if applicable) in sub-group of participants with CIS only	Month 6
Event-free survival	Event-free survival (EFS) of intravesical TARA-002 compared to Investigator's choice of intravesical chemotherapy	Up to Month 60
Recurrence-free survival	Recurrence-free survival (RFS) of intravesical TARA-002 compared to Investigator's choice of intravesical chemotherapy	Up to Month 60
Progression-free survival	Progression-free survival (PFS) of intravesical TARA-002 compared to Investigator's choice of intravesical chemotherapy	Up to Month 60
Disease-specific progression-free survival	Disease-specific progression-free survival (DSPFS) of intravesical TARA-002 compared to Investigator's choice of intravesical chemotherapy	Up ro Month 60
Overall survival	Overall survival (OS) of intravesical TARA-002 compared to Investigator's choice of intravesical chemotherapy	Up to Month 60
Disease-specific survival	Disease-specific survival (DSS) of intravesical TARA-002 compared to Investigator's choice of intravesical chemotherapy	Up to Month 60
Time to cystectomy	Time to cystectomy of intravesical TARA-002 compared to Investigator's choice of intravesical chemotherapy	Up to Month 60
Time to recurrence delayed cystectomy	Time to recurrence delayed cystectomy of intravesical TARA-002 compared to Investigator's choice of intravesical chemotherapy	Up to Month 60
Time to progression	Time to progression of intravesical TARA-002 compared to Investigator's choice of intravesical chemotherapy	Up to Month 60
Time to disease worsening	Time to disease worsening of intravesical TARA-002 compared to Investigator's choice of intravesical chemotherapy	Up to Month 60

Collaborators and Investigators

• Sponsor: Protara Therapeutics

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): November 1, 2032

Study Registration Dates

• First Submitted: March 13, 2026
• First Submitted That Met QC Criteria: March 13, 2026
• First Posted (Actual): March 18, 2026

Study Record Updates

• Last Update Posted (Actual): March 18, 2026
• Last Update Submitted That Met QC Criteria: March 13, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: bladder cancer; carcinoma in situ; Non-muscle invasive bladder Cancer; BCG-naive
• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Urologic Neoplasms; Carcinoma; Urinary Bladder Diseases; Non-Muscle Invasive Bladder Neoplasms; Neoplasms; Carcinoma in Situ; Urinary Bladder Neoplasms
• Other Study ID Numbers: TARA-002-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No