Evaluating RAG-01 for patients with bladder cancer who didn't respond to BCG therapy

A Phase Ⅰ, Open Label, Multi-center Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of RAG-01 in Patients With Non-muscle-invasive Bladder Cancer (NMIBC) Who Have Failed Bacillus Calmette Guérin (BCG) Therapy

This study is testing a new treatment called RAG-01 for people with bladder cancer who didn't get better after standard BCG therapy to see if it works and is safe.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 72 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Ractigen Therapeutics. (Academic / other)
• Locations: 3 sites (St Leonards, New South Wales and 2 other locations)
• Trial ID: NCT06351904 on ClinicalTrials.gov

What this trial studies

This open-label, multi-center clinical trial aims to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of RAG-01 in patients diagnosed with non-muscle-invasive bladder cancer (NMIBC) who have previously failed Bacillus Calmette Guérin (BCG) therapy. The study will utilize a '3+3' dose escalation design, which includes a screening phase, a treatment phase with dose-limiting toxicity assessments, and a follow-up period. Participants will be closely monitored to evaluate the drug's effects and any potential side effects.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 to 75 with high-grade NMIBC who have failed prior BCG treatment.

Not a fit: Patients with allergies to RAG-01 or similar products may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with NMIBC who have not responded to standard BCG therapy.

How similar studies have performed: While this approach is novel in the context of RAG-01, similar studies targeting NMIBC have shown promise in exploring alternative therapies after BCG failure.

Eligibility criteria

Inclusion Criteria:

1. Ability to understand the study and have signed the informed consent form;
2. Any adult ≥ 18 years old;
3. Pathologically confirmed high grade NMIBC defined as grade 2 or grade 3 disease;
4. Expected survival ≥ 6 months;
5. ECOG PS ≤2;
6. Sufficient organ functions, as defined below:

   Investigations Hematology Absolute Neutrophil Count (ANC): ≥ 1.5 x 109/L Hemoglobin: ≥ 90 g/L Platelet: ≥ 100 x 109/L Liver Function Serum bilirubin: ≤ 1.25×ULN or 2.5×ULN（with Gilbert syndrome） AST \& ALT: ≤ 2.5×ULN Renal Function Creatinine Clearance (Cockcroft-Gault equation): ≥ 30 mL/min
7. Subject must be able to tolerate catheterization;
8. Female subject of childbearing potential and her spouse must use adopt effective contraception (non-pharmacological contraception required) from signing informed consent to within 6 months after the last instillation;

Exclusion Criteria:

1. Subject who is allergy to RAG-01 or similar products;
2. Except for TURBT, the subject received other anti-tumor treatments, and the last administration date is within ≤ 21 days or 5 half-lifes whichever is shorter from the date of signing ICF;
3. Subject with imaging examination diagnosed extravesical metastasis, including ureter and urethra;
4. Subject has other malignancies within the past 3 years, except for adequately treated carcinoma of the cervix, basal or squamous cell carcinomas of the skin, or adenocarcinoma of the prostate that has been surgically treated with a post-treatment PSA that is non-detectable;
5. The following illnesses have not been relieved to CTCAE 0-1:

   1. Uncontrolled acute and chronic infections, such as pneumonia, biliary tract infection, hepatitis B virus infection and hepatitis C virus infection;
   2. Dyspnea;
   3. Acute and chronic kidney injury, and inflammation;
   4. Urinary incontinence;
   5. Urinary frequency;
   6. Urinary tract obstruction (except benign prostatic hypertrophy);
6. Subject could not hold the urine for at least 90 mins due to any reason;
7. New York Heart Association (NYHA) 3 or 4 grade;
8. Coronary heart disease related symptoms have not been relieved to CTCAE 0-1, including: myocardial infarction, unstable angina pectoris, congestive heart failure and arrhythmia;
9. Subject with QTc \>470 msec.
10. Cerebrovascular accidents have not been relieved to CTCAE 0-1;
11. HIV positive; Active hepatitis B or C. For active HBV, it's defined as HBsAg positive with HBV DNA ≥ ULN, for active HCV, it's defined as HCV antibody positive with HCV RNA ≥ ULN, respectively.
12. Subject is pregnant or lactating during the treatment period;
13. History of central nervous system or psychiatric disorders, e.g., epilepsy or dementia;
14. Other severe systemic diseases which might compromise the subject's compliance to the study, e.g., uncontrolled diabetes, gastrointestinal disorders, and renal diseases;
15. Any other situations which are judged by the investigator, would exposure the subject to unnecessary risk, therefore he/she is not eligible.

Where this trial is running

St Leonards, New South Wales and 2 other locations

• GenesisCare North Shore — St Leonards, New South Wales, Australia (Recruiting)
• The Royal Melbourne Hospital — Melbourne, Victoria, Australia (Recruiting)
• Peninsula & South Eastern Haematology and Oncology Group — Melbourne, Victoria, Australia (Recruiting)

Study contacts

• Principal investigator: Laurence Krieger, MBCHB — GenesisCare, 7 Westbourne Street, St Leonards, NSW 2065, Australia
• Study coordinator: Long-Cheng Li

Conditions Non-Muscle-Invasive Bladder Cancer