ASCO 2023: ADVANCED-2: 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 NMIBC

( The 2023 ASCO annual meeting included a bladder cancer session, featuring a trials in progress presentation by Dr. Wei Sun discussing 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 NMIBC. Bladder cancer is the most common malignancy involving the urinary system, is the 6th most common cancer in the United States, and leads to 18,000 deaths each year. Additionally, approximately 80% of new urothelial bladder cancer cases are classified as non-muscle invasive bladder cancer (NMIBC).

With the current BCG shortage and limited effective alternate therapies, there continues to be a significant unmet need for treatment options for patients with NMIBC. TARA-002 is a lyophilized biological preparation for instillation containing cells of Streptococcus pyogenes (Group A, type 3) Su strain treated with benzylpenicillin. The chemical characteristics of TARA-002 are intended to be comparable to OK-432, which is approved in Japan and Taiwan for the treatment of several different cancers (head and neck, gastric, and lung cancer). The antitumor activity of TARA-002 and OK-432 is thought to occur by direct cytotoxicity and by stimulation of immunocompetent cells through the induction of helper T-cell type-1 cytokines, which then recruit cytotoxic T lymphocytes to tumor cells. As such, nonclinical and clinical evidence with OK-432 and TARA-002 support the ADVANCED-1 study (dose escalation Phase 1a [NCT05085977] and dose expansion Phase 1b/2 [NCT05085990]). The dose for the planned Phase 1b/2 study (ADVANCED-1-Ph1b/2) will be based on the recommended Phase 2 dose established in the Phase 1a study.

ADVANCED-2 is a Phase 1b/2, dose expansion, open-label study of intravesical instillation of TARA-002 in adults with high grade carcinoma in situ NMIBC. The purpose of this study is to evaluate the safety and anti-tumor activity of TARA-002 administered intravesically for the treatment of subjects with carcinoma in situ NMIBC (± Ta/T1) with active disease. The study includes 102 eligible male and female subjects ≥ 18 years of age enrolled in two cohorts based on their prior BCG experience. Inclusion and exclusion criteria are as follows: 

ADVANCED 2 criteria

Cohort A (n=27) includes subjects unable to obtain BCG or subjects who have not received BCG in the last 24 months prior to carcinoma in situ diagnosis, and Cohort B (n=75) includes subjects with carcinoma in situ who are BCG unresponsive after completion of adequate BCG therapy (at least 5 of 6 doses of an initial induction course plus either at least 2 of 3 doses of maintenance therapy or at least 2 of 6 doses of a second induction course). The trial design for ADVANCED-2 is as follows:

ADVANCED 2 cohort flow chart

Those with current or a history of penicillin allergy or current evidence of any condition, therapy, or laboratory abnormality that might confound the results are excluded. The overall study duration is 6 months/24 weeks per subject for Ph1b/2-Cohort A (includes induction, reinduction if applicable), and 24 months/96 weeks per subject for Ph1b/2-Cohort B (includes induction, reinduction if applicable, maintenance until 18 months).

Dr. Sun concluded his presentation by highlighting several points:

  • The ADVANCED-1 study is ongoing and will provide further evidence of safety and initial anti-tumor activity of TARA-002 in patients with high-grade CIS NMIBC at the 3-month time point at the established recommended Phase 2 dose of 40 KE
  • The ADVANCED-2 study will provide further evidence of safety and anti-tumor activity of TARA-002 in patients with high-grade carcinoma in situ +/- Ta/T1 NMIBC
  • The ADVANCED-1 study started in March 2022, with the phase 1b (ADVANCED-1EXP) open for enrollment
  • Phase 1b/2 (ADVANCED-2) is expected to begin enrollment in August 2023

Presented by: Wei Sun, MD, Protara Therapeutics, New York, NY

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 2 – Tues, June 6, 2023.