Phase 3 trial — bladder cancer virus therapy, BOND-003 cohort C (NCT04452591), published in The Lancet Oncology, July 2026 · FDA Breakthrough Therapy designation
Bladder cancer virus therapy cretostimogene grenadenorepvec produced a complete response in 75.5% of patients with high-risk, BCG-unresponsive non-muscle invasive bladder cancer with carcinoma in situ in a phase 3 trial. The results were published in The Lancet Oncology in July 2026, and about 90% of patients who were in response at 12 months were still in response at two years. In the United States, the company plans to complete its approval filing in the fourth quarter of 2026.
What is cretostimogene, the bladder cancer virus therapy?
Cretostimogene is an oncolytic virus therapy developed by the U.S. company CG Oncology. Oncolytic viruses are designed to multiply inside cancer cells and burst them, and they belong to the wider family of gene therapies because they carry genes into cells. Our oncolytic virus therapy guide explains the principle and other approved products.
The virus takes advantage of Rb-E2F pathway alterations that are common in cancer cells, so it multiplies selectively inside them. When the cancer cells break open, tumor antigens are released and the immune system learns to recognize the cancer, while a GM-CSF gene carried by the virus strengthens that immune response. The treatment therefore works in two ways at once: it destroys cancer cells directly and it wakes up the immune system.
Which bladder cancer patients is it for?
Bladder cancer that has not grown into the muscle layer is called non-muscle invasive bladder cancer (NMIBC). When the risk of recurrence is high, patients receive BCG, a tuberculosis vaccine placed into the bladder after endoscopic removal of the tumor. If cancer persists or returns after BCG (BCG-unresponsive disease), the standard option is radical cystectomy, removal of the whole bladder. Because this is major surgery that requires a new urinary route, many patients look for treatments that preserve the bladder.
Cohort C of this phase 3 trial enrolled patients with BCG-unresponsive high-risk NMIBC that included carcinoma in situ (CIS, a flat high-grade cancer spreading along the bladder lining), with or without papillary tumors. A different approach for the same condition, a drug that activates NK cells, is covered in BCG-unresponsive bladder cancer: Anktiva.
How is the treatment given?
It is not an injection or systemic chemotherapy. The drug is placed directly into the bladder through a urinary catheter, much like BCG, so it can be given in an outpatient clinic. An excipient called DDM, which helps the virus reach the bladder lining, is instilled first, followed by the virus.
- Induction: once a week for 6 weeks
- Maintenance: further doses at set intervals after induction
- Preparation: in the trial, no preventive anticholinergic drugs, operating room, anesthesia or extra cystoscopy were needed.
Phase 3 results: 75.5% complete response, 81% bladder preservation at 2 years
The evidence comes from the single-arm phase 3 BOND-003 cohort C. The lead author is Dr. Mark D. Tyson of Mayo Clinic. A total of 115 patients enrolled across North America, Australia and the Asia-Pacific region, and 112 received at least one dose. Complete response means no cancer is seen on cystoscopy, biopsy and urine cytology.
| Measure | Result |
|---|---|
| Complete response rate (at any time) | 75.5% (95% CI 66.3–83.2%) |
| Duration of response at 12 months | 64.2% (52.2–73.8%) |
| Duration of response at 24 months | 60.1% (48.2–70.0%) |
| Median duration of response | At least 27.9 months (not yet reached) |
| Free from progression to muscle-invasive disease | 96.6% (48 and 96 weeks) |
| Kept the bladder (cystectomy-free) | About 89% at 12 months, about 81% at 24 months |
Source: BOND-003 cohort C, The Lancet Oncology 2026;27(8):983–993 (reported by Targeted Oncology; CG Oncology release 2026-07-27). Duration-of-response rates refer to patients who reached complete response.
About 90% of patients who were in response at 12 months remained in response at 24 months, and one patient has stayed cancer-free for more than 51 months. Dr. Tyson said that, if approved, cretostimogene may be an important bladder-sparing advance in bladder cancer treatment. Progression to muscle-invasive disease occurred in 3.4% of patients.
What are the side effects and how are they managed?
There were no treatment-related grade 3 or higher adverse events, no discontinuations because of side effects and no treatment-related deaths. The most common symptoms were bladder spasm, frequent urination, urgency, painful urination and blood in the urine. These are typical of treatments placed into the bladder, and the median time for them to resolve was 1 day. If symptoms persist, tell your care team so they can help manage them.
Approval timeline and where it is available
Cretostimogene has Fast Track and Breakthrough Therapy designations from the U.S. FDA. In its November 6, 2026 update, the company said it plans to complete its Biologics License Application (BLA) for BCG-unresponsive disease with CIS in the fourth quarter of 2026. In North America, an Expanded Access Program lets eligible BCG-unresponsive patients receive the drug before approval.
Research is also expanding to other stages. Topline results from the phase 3 PIVOT-006 trial in intermediate-risk bladder cancer are expected in November 2026, and 12-month data from the papillary-only cohort and from the CORE-008 study in BCG-exposed patients are expected in December 2026. More than 700 NMIBC patients are taking part in the company's program overall. As of November 2026, no country, including Japan, has granted full approval yet, so the treatment is currently available through clinical trials or expanded access. For gene therapy in general, see What is cancer gene therapy and our nucleic acid medicine & aptamers guide.
What to check and questions for your doctor
- Does my bladder cancer meet the definition of BCG-unresponsive disease? Do I have carcinoma in situ?
- Besides radical cystectomy, which bladder-sparing treatments suit me?
- Is there a cretostimogene clinical trial or expanded access program I could join?
- How often will I need cystoscopy and biopsy during treatment?
Frequently asked questions
How is bladder cancer virus therapy given?
The virus is placed directly into the bladder through a urinary catheter. In the trial, patients received weekly induction for 6 weeks followed by maintenance, without anesthesia or an operating room.
What is the complete response rate of cretostimogene?
It was 75.5% in phase 3 BOND-003 cohort C. Among responders, the 24-month duration-of-response rate was 60.1%.
Do I have to have my bladder removed if BCG stops working?
Radical cystectomy is the standard option, but new bladder-sparing treatments are approved or available through trials. In this study, about 81% of patients kept their bladder at 24 months.
When will cretostimogene be approved?
The company plans to complete its U.S. approval filing in the fourth quarter of 2026. The approval date depends on the FDA review.
Sources
- The Lancet Oncology — Intravesical cretostimogene grenadenorepvec oncolytic immunotherapy in high-risk BCG-unresponsive NMIBC with carcinoma in situ (BOND-003 cohort C): a single-arm, phase 3 trial (2026;27(8):983–993)
thelancet.com
Checked: 2026-11-07 - Targeted Oncology — Durable responses seen with cretostimogene in BCG-unresponsive NMIBC (2026-07-29)
targetedonc.com
Checked: 2026-11-07 - CG Oncology — Publication of pivotal phase 3 BOND-003 cohort C study results in The Lancet Oncology (2026-07-27)
1stoncology.com
Checked: 2026-11-07 - CG Oncology — Form 8-K, third quarter 2026 business update (U.S. SEC, 2026-11-06)
sec.gov
Checked: 2026-11-07 - Society of Urologic Oncology — cretostimogene abstract: mechanism and dosing schedule
suo-abstracts.secure-platform.com
Checked: 2026-11-07
Written by the FTH editorial team, sources checked 2026-11-07 · Medical review: none
This article is general information based on public sources and does not replace diagnosis or treatment. Please discuss treatment decisions with your care team.
