Safety and Toxicity Study of Intravesical Instillation of TARA-002 in Adults With High-grade Non-muscle Invasive Bladder Cancer

Study Overview
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Brief Summary
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This study is open-label dose expansion study to investigate the safety and toxicity of intravesical treatment of high-grade NMIBC (HGTa or CIS, including CIS with consomitant Ta) after transurethral resection of bladder tumor (TURBT) and/or biopsy using TARA-002 in adults unable to obtain intravesical Bacillus Calmette-Guérin (BCG), adults who have received at least one dose of intravesical BCG or adults who have received at least one dose of intravesical chemotherapy. After completion of the dose escalation phase (Phase 1a) and after the RP2D has been established, the dose expansion phase (Phase 1b) will start enrollment of subjects with CIS NMIBC with active disease to further evaluate the safety and preliminary efficacy of TARA-002, at the established RP2D. CIS NMIBC with active disease is defined as disease present at the last cystoscopic evaluation prior to signing the ICF. Subjects enrolled in the dose expansion phase will not include subjects previously enrolled and treated in the dose escalation phase. All subjects will receive 6 weeks of treatment at the established RP2D.

Official Title
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A Phase 1a/b Dose Finding, Open-label Study to Evaluate Safety and Toxicity of Intravesical Instillation of TARA-002 in Adults With High-grade Non-muscle Invasive Bladder Cancer

Conditions
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Non-muscle Invasive Bladder Cancer

Intervention / Treatment
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* Biological: TARA-002


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects 18 years of age or older at the time of signing the informed consent Subjects who have voluntarily given written informed consent after the nature of the study has been explained according to applicable requirements prior to study entry Subjects with a histologically confirmed, high-grade Ta or CIS (including CIS with concomitant Ta) urothelial cell carcinoma of the bladder according to central review Subjects who are treatment naïve, unable to obtain intravesical BCG for the treatment of NMIBC, have received at least one dose of intravesical BCG, or at least one dose of intravesical chemotherapy Exclusion Criteria: Penicillin allergy (subjects with a questionable history of allergy to penicillin or no history of penicillin use will undergo penicillin allergy testing prior to inclusion in the study) Predominant (defined as > 50%) adenocarcinoma, squamous cell carcinoma, or histological variants including plasmacytoid, sarcomatoid, or squamous components according to central review Concomitant prostatic or upper tract urothelial involvement per Investigator's assessment Nodal involvement or metastatic disease that existed at any time (past or present disease) Bladder cancer stage ≥ T1 within the last 36 months according to central histology review Bladder cancer stage CIS with concomitant T1 For more information on eligibility criteria, please contact the sponsor.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: All subjects will receive 6 weekly doses of TARA-002 at the recommended Phase 2 dose (R2PD)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TARA-002<br>TARA-002 is a lyophilized biological preparation for instillation containing cells of Streptococcus pyogenes (Group A, type 3) Su strain treated with benzylpenicillin. | Biological: TARA-002<br>* Phase 1b, Dose Expansion Phase: All subjects will receive 6 weekly doses of TARA-002 at the recommended Phase 2 dose (R2PD)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1b, Dose Expansion Phase: Incidence of AEs in subjects with CIS NMIBC with active disease | AE = adverse event | Day 1 to Day 78 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-muscle invasive bladder cancer, bladder cancer, high grade Ta, carcinoma in situ, high-grade NMIBC