ADVANCED-2: Dose Expansion, Safety and Efficacy Study of Intravesical Instillation of TARA-002 in Adults With High-grade Non-muscle Invasive Bladder Cancer

Sponsor

Protara Therapeutics (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05951179

Collaborator

(none)

102

Enrollment

Arm

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

TARA-002-101-Ph1b/2 is an open-label Phase 1b/2 dose expansion study to investigate the safety and anti-tumor activity of intravesical treatment of high-grade CIS NMIBC (± Ta/T1) with intravesical instillation of TARA-002 in adults 18 years of age or older.

The Phase 1b/2 study (TARA-002-101-Ph1b/2) will be initiated after the RP2D has been established in the Phase 1a dose finding study (TARA-002-101-Ph1a).

This Phase 1b/2 (TARA-002-101-Ph1b/2) dose expansion study includes participants with CIS NMIBC (± Ta/T1) with active disease (defined as disease present at last tumor evaluation prior to signing ICF).

Participants will be enrolled into one of 2 cohorts:

Cohort A:

Participants with CIS (± Ta/T1) who are unable to obtain intravesical BCG, or
Participants with CIS (± Ta/T1) who have not received intravesical BCG for 24 months prior to CIS diagnosis

Cohort B:

Participants with CIS (± Ta/T1) who are BCG unresponsive after completion of adequate BCG therapy (minimum 5/6 doses induction and 2/3 doses maintenance or 2/6 doses reinduction)

Condition or Disease	Intervention/Treatment	Phase
Non-muscle Invasive Bladder Cancer	Biological: TARA-002	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

102 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Cohort A: All participants will receive 6 weekly instillations of TARA-002 at the established recommended Phase 2 dose (RP2D). Participants who are eligible for reinduction will receive 6 additional weekly doses of TARA-002 instillation as part of the Second Treatment Period. Cohort B: All participants will receive 6 weekly instillations of TARA-002 at the established RP2D. Participants who are eligible for reinduction will receive 6 additional weekly doses of TARA-002 instillation as part of the Second Treatment Period. Participants confirmed to have a complete response will receive 3 additional weekly doses of TARA-002 instillation as part of the Second Treatment Period. All eligible participants will receive 3 weekly doses of TARA-002 instillation as part of the Third Treatment Period (maintenance) at Months 6, 9, 12, 15, and 18.Cohort A: All participants will receive 6 weekly instillations of TARA-002 at the established recommended Phase 2 dose (RP2D). Participants who are eligible for reinduction will receive 6 additional weekly doses of TARA-002 instillation as part of the Second Treatment Period. Cohort B: All participants will receive 6 weekly instillations of TARA-002 at the established RP2D. Participants who are eligible for reinduction will receive 6 additional weekly doses of TARA-002 instillation as part of the Second Treatment Period. Participants confirmed to have a complete response will receive 3 additional weekly doses of TARA-002 instillation as part of the Second Treatment Period. All eligible participants will receive 3 weekly doses of TARA-002 instillation as part of the Third Treatment Period (maintenance) at Months 6, 9, 12, 15, and 18.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1b/2, Dose Expansion, Open-label Study to Evaluate Safety and Anti-tumor Activity, of Intravesical Instillation of TARA-002 in Adults With High-grade Non-muscle Invasive Bladder Cancer

Anticipated Study Start Date :

Jul 1, 2023

Anticipated Primary Completion Date :

May 31, 2026

Anticipated Study Completion Date :

May 31, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TARA-002 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 Cohort A: All subjects will receive 6 weekly instillations of TARA-002 at the established recommended Phase 2 dose (RP2D). Subjects who are eligible for reinduction will receive 6 additional weekly doses of TARA-002 instillation as part of the Second Treatment Period. Cohort B: All subjects will receive 6 weekly instillations of TARA-002 at the established RP2D. Subjects who are eligible for reinduction will receive 6 additional weekly doses of TARA-002 instillation as part of the Second Treatment Period. Subjects confirmed to have a complete response will receive 3 additional weekly doses of TARA-002 instillation as part of the Second Treatment Period. All eligible subjects will receive 3 weekly doses of TARA-002 instillation as part of the Third Treatment Period (maintenance) at Months 6, 9, 12, 15, and 18.

Arm

Intervention/Treatment

Experimental: TARA-002

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

Cohort A: All subjects will receive 6 weekly instillations of TARA-002 at the established recommended Phase 2 dose (RP2D). Subjects who are eligible for reinduction will receive 6 additional weekly doses of TARA-002 instillation as part of the Second Treatment Period. Cohort B: All subjects will receive 6 weekly instillations of TARA-002 at the established RP2D. Subjects who are eligible for reinduction will receive 6 additional weekly doses of TARA-002 instillation as part of the Second Treatment Period. Subjects confirmed to have a complete response will receive 3 additional weekly doses of TARA-002 instillation as part of the Second Treatment Period. All eligible subjects will receive 3 weekly doses of TARA-002 instillation as part of the Third Treatment Period (maintenance) at Months 6, 9, 12, 15, and 18.

Outcome Measures

Primary Outcome Measures

Cohort A: Incidence of high-grade Complete Response at any time after treatment with TARA-002 [Month 3 to Month 6]
Cohort A: Incidence of high-grade Complete Response at any time by subgroup (BCG naive and BCG exposed > 24 months) after treatment with TARA-002 [Month 3 to Month 6]
Cohort B: Incidence of high-grade Complete Response at any time after treatment with TARA-002 [Month 3 to Month 24]

Secondary Outcome Measures

Cohort A: Incidence and severity of AEs, TEAEs, SAEs and TESAEs after treatment with TARA-002 [Day 1 to Month 6]
AE = adverse event; TEAE = treatment emergent adverse event; SAE = serious adverse event; TESAE = treatment emergent serious adverse event
Cohort A: Change from baseline in inflammatory urine cytokines levels (including IL-6, IL-8, IFN-γ, and TNF-α) after treatment with TARA-002 [Day 1 to Month 6]
Cohort A: Quality of Life based on the EORTC questionnaire QLQ-NMIBC24 [Day 1 to Month 6]
EORTC = European Organization for Research and Treatment of Cancer; QLQ-NMIBC24 = Questionnaire for Patients with NMIBC
Cohort A: Quality of Life based on the EORTC questionnaire QLQ-C30 [Day 1 to Month 6]
EORTC = European Organization for Research and Treatment of Cancer; QLQ-C30 = Questionnaire for Patients with Cancer
Cohort B: Duration of high-grade Complete Response after treatment with TARA-002 [Month 3 to Month 24]
Cohort B: High-grade Complete Response rate at Months 3, 6, 9, 12, 15, 18, 21, and 24 after treatment with TARA-002 [Month 3 to Month 24]
Cohort B: Duration of Complete Response (all recurrent bladder cancer, including low grade Ta) after treatment with TARA-002 [Month 3 to Month 24]
Cohort B: Complete Response rate (all recurrent bladder cancer, including low grade Ta) at Months 3, 6, 9, 12, 15, 18, 21, and 24 after treatment with TARA-002 [Month 3 to Month 24]
Cohort B: Progression free survival after treatment with TARA-002 [24 months]
Cohort B: Disease-specific progression free survival after treatment with TARA-002 [24 months]
Cohort B: Overall survival after treatment with TARA-002 [24 months]
Cohort B: Disease specific survival after treatment with TARA-002 [24 months]
Cohort B: Time to cystectomy after treatment with TARA-002 [24 months]
Cohort B: Time to recurrence delayed cystectomy after treatment with TARA-002 [24 months]
Cohort B: Time to progression after treatment with TARA-002 [24 months]
Cohort B: Time to disease worsening after treatment with TARA-002 [24 months]
Cohort B: Incidence and severity of AEs, TEAEs, SAEs and TESAEs after treatment with TARA-002 [Day 1 to Month 24]
Cohort B: Change from baseline in inflammatory urine cytokines levels (including IL-6, IL-8, IFN-γ, and TNF-α) after treatment with TARA-002 [Day 1 to Month 24]
Cohort B: Quality of Life based on the EORTC questionnaire QLQ-NMIBC24 [Day 1 to Month 24]
EORTC = European Organization for Research and Treatment of Cancer; QLQ-NMIBC24 = Questionnaire for Patients with NMIBC
Cohort B: Quality of Life based on the EORTC questionnaire QLQ-C30 [Day 1 to Month 24]
EORTC = European Organization for Research and Treatment of Cancer; QLQ-C30 = Questionnaire for Patients with Cancer

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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
Central histologic confirmation of high-grade non-muscle invasive CIS (± Ta/T1) with active disease
Subjects who are unable to obtain intravesical BCG, have not received intravesical BCG for 24 months prior to CIS diagnosis, or have persistent or recurrent CIS (± Ta/T1) within 12 months of completion of adequate BCG

Exclusion Criteria:

Penicillin allergy (subjects with a questionable history of allergy to penicillin will undergo penicillin blood allergy testing via central laboratory
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 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 subject's history

For more information on eligibility criteria, please contact the Sponsor