Oncolytic viral therapy for bladder cancer

Oncolytic Virus (OH2) Adjuvant Therapy After Transurethral Resection of Bladder Tumor in Non-Muscle-Invasive Bladder Cancer Who Have Failed First-line Prophylactic Intravesical Instillation Therapy: a Phase Ⅰb/Ⅱ Clinical Trial

This study is testing a new virus treatment for bladder cancer to see if it helps patients who haven't had success with standard therapy.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Binhui Biopharmaceutical Co., Ltd. (Industry-sponsored)
• Drugs / interventions: chemotherapy, radiation
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT05232136 on ClinicalTrials.gov

What this trial studies

This phase Ⅰb/Ⅱ study evaluates the safety and efficacy of OH2, an oncolytic virus derived from herpes simplex virus type 2, as an adjuvant therapy for patients with non-muscle-invasive bladder cancer who have failed first-line prophylactic intravesical instillation therapy. The trial involves a single-arm, multicenter approach where participants receive OH2 through intravesical instillation, with treatment occurring every two weeks during the induction period and monthly during maintenance. The study aims to assess the antitumor immune response induced by OH2, alongside monitoring adverse events and disease recurrence through various examinations.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 to 80 with high-grade non-muscle-invasive bladder cancer who have failed first-line preventive therapy and are not suitable for radical cystectomy.

Not a fit: Patients with muscle-invasive bladder cancer or those who have undergone systemic chemotherapy or radiation therapy for bladder cancer may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a new treatment option for patients with non-muscle-invasive bladder cancer who have not responded to standard therapies.

How similar studies have performed: Other studies utilizing oncolytic viruses have shown promise, suggesting that this approach may be effective, although this specific application is novel.

Eligibility criteria

Inclusion Criteria:

1. Age 18 \~ 80 years old (including boundary value), male or female.
2. Failed in first-line preventive bladder perfusion therapy, and retained the bladder (or other reasons are not suitable for radical total cystectomy).
3. Ta, T1 or Tis with high grade (HG) of non-muscle-invasive bladder cancer.
4. Negative histology and pathology of bladder mucosa biopsy and negative postoperative urine cytology during TURBT.
5. No tumor was found in upper urinary tract examination; No systemic chemotherapy or radiation therapy for bladder cancer has been done at any time before.
6. ECOG 0-1.
7. The estimated survival time is more than 1 year.
8. Laboratory inspection:

   1. WBC≥3.5 × 10\^9／L，ANC≥1.5 × 10\^9／L，PLT≥80 × 10\^9／L，Hb≥90g/L；
   2. Blood bun and serum creatinine were within 1.5 times of the upper limit of normal value;
   3. TBIL ≤ 1.5 times the upper limit of normal value;
   4. ALT and AST ≤ 2.5 times the upper limit of normal value;
   5. The coagulation function is normal (PT and APTT are within 1.5 times of the upper limit of normal value).
9. Received effective contraception during and within 3 months after treatment.
10. At least 3 months after the end of herpes infection.
11. Voluntary signing of informed consent, expected patient compliance

Exclusion Criteria:

1. muscle invasive bladder cancer or bladder cancer with clinical metastasis.
2. Complications occurred after TURBT, or perfusion therapy could not be performed.
3. Allergic to GM-CSF products or have a history of allergic reaction to the main and auxiliary materials of any dosage form in the study drug.
4. Suffering from serious medical diseases, including severe heart disease, cerebrovascular disease, uncontrolled diabetes, uncontrolled hypertension, severe infection, active gastrointestinal ulcer.
5. Chemotherapy or radiotherapy is expected to be used during the study.
6. Active infection or fever of unknown cause \> 38.5 ℃ during screening and before the first administration. Ongoing urinary system infection, especially bladder infection (if the infection can be controlled by antibiotics, except that it can return to normal after 7 days of antibiotic withdrawal).
7. Congenital or acquired immune deficiency (such as HIV infection) , Hepatitis B infection of HBV-DNA or more than 10 /mL, HCV antibody and HCV RNA positive in hepatitis C infection.
8. Pregnant or lactating.
9. Other experimental drugs or antiviral therapy were used or are being used within 4 weeks before treatment.
10. Participated in immunosuppressive therapy in recent 3 months, including cyclosporine, antithymocyte globulin or tacrolimus.
11. Participated in cancer vaccine treatment trials in recent 12 months (such as dendritic cell therapy and heat shock vaccine).
12. History of psychotropic substance abuse, alcoholism or drug abuse.
13. Other malignant tumors within 5 years before enrollment, except effectively resected cervical carcinoma in situ, low-risk gastrointestinal stromal tumor, skin basal cell carcinoma, skin squamous cell carcinoma, thyroid papillary carcinoma and breast ductal carcinoma in situ.
14. Active autoimmune diseases or history of autoimmune diseases and may relapse, except:

    1. Type I diabetes mellitus;
    2. Hypothyroidism (if only controlled by hormone replacement therapy);
    3. Controlled celiac disease;
    4. Skin diseases that do not require systemic treatment (such as vitiligo, psoriasis, hair loss);
    5. Any other disease that will not recur without external triggers.
15. Using corticosteroids within 14 days before the administration of the study drug due to treatment, or suffering from any disease requiring systemic treatment with other immunosuppressants, except:

    1. Local, ophthalmic, intra-articular, intranasal or inhaled corticosteroids with minimal systemic absorption;
    2. Prophylactic short-term use of corticosteroids (e.g., allergy to contrast agents) or for the treatment of non autoimmune diseases (e.g., delayed hypersensitivity caused by contact allergens).
16. Not suitable to participate study judged by investigators for any reason.

Where this trial is running

Beijing, Beijing Municipality

• National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College — Beijing, Beijing Municipality, China (Recruiting)

Study contacts

• Study coordinator: JianZhong Shou, MD

Conditions Non-muscle-invasive Bladder Cancer; Oncolytic Virus