Safety and Toxicity Study of Intravesical Instillation of TARA-002 in Adults With High-grade Non-muscle Invasive Bladder Cancer (Phase 1a)

Study Overview
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Brief Summary
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This study is an open-label dose escalation study (Phase 1a) to investigate the safety and toxicity of intravesical treatment of high-grade NMIBC (HGTa or CIS, including CIS with concomitant 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. Dosing will start in subjects with HGTa or CIS (including CIS with concomitant Ta), and all subjects will receive 6 weeks of treatment at a fixed volume with varying dose levels.

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 on central review Subjects who are treatment naïve, are 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 blood 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: Sequential Assignment
Interventional Model Description: First, up to 3 dose levels of TARA-002 (10 KE → 20 KE → 40 KE) will be tested sequentially with 6 weekly intravesical doses starting with the lowest dose using a 3+3 design in a dose escalation manner until the RP2D has been established. If the MTD is not reached, additional cohorts of dose levels higher than 40 KE may be explored.
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 1a, Dose Escalation: First, up to 3 dose levels of TARA-002 (10 KE → 20 KE → 40 KE) will be tested sequentially with 6 weekly intravesical doses starting with the lowest dose using a 3+3 design in a dose escalation manner until the RP2D has been established. If the MTD is not reached, additional cohorts of dose levels higher than 40 KE may be explored.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1a, Dose Escalation Phase: Incidence of DLT AEs in subjects with HGTa or CIS NMIBC | DLT = dose limiting toxicities; HGTa = high grade Ta; CIS = carcinoma in situ, includes CIS with concomitant Ta | Day 1 to Day 43 | 
| Phase 1a, Dose Escalation Phase: MTD and RP2D of TARA-002 in subjects with HGTa or CIS NMIBC | MTD = maximum tolerated dose; RP2D = recommended Phase 2 dose | Day 1 to Day 43 | 

 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