BOND-003 Phase 3 Results Published in Lancet Oncology: Durable Response With Cretostimogene in BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer

KEY FINDINGS

• Complete response (CR): 75.5% at any time (83/110 patients; 95% CI 66.3-83.2) - significantly above historical benchmarks.
• Durability of response: Median duration of response 27.9 months; approximately 90% of patients in response at month 12 maintained their response at month 24.
• Bladder preservation: Cystectomy-free survival was 89% at month 12 and 81% at month 24.
• Progression: Progression to muscle-invasive disease occurred in only 4 patients (3.4%); the progression-free rate was 96.6% at weeks 48 and 96.
• Safety: No grade ≥3 treatment-related adverse events, treatment-related deaths or treatment discontinuations were reported.

Clinical Context: The Scale of the Unmet Need

BCG-unresponsive, high-risk non-muscle-invasive bladder cancer (NMIBC) is one of the most challenging clinical scenarios in contemporary uro-oncology. In this patient group, which includes carcinoma in situ (CIS), the guideline-recommended standard approach is radical cystectomy. However, cystectomy is a heavy decision for the patient because of urinary diversion, loss of sexual function and permanent changes in quality of life. Particularly in this population, where the median age is above 70, the burden of comorbidity makes radical surgery either high-risk or unacceptable for many patients.

Developing bladder-sparing treatments has therefore become a priority goal for the field. Cretostimogene grenadenorepvec is an intravesically administered oncolytic immunotherapy engineered to replicate selectively in tumour cells with a disrupted retinoblastoma-E2F pathway. The agent both exerts a direct oncolytic effect and strengthens the immune response against the tumour.

Study Design

BOND-003 Cohort C (NCT04452591) is a single-arm, international phase 3 trial conducted at 41 academic and community centres in North America, Asia-Pacific and Australia. The results were published in The Lancet Oncology on 27 July 2026.

Key Results

Safety Profile

Treatment-related adverse events were reported in 63% of patients and consisted predominantly of grade 1-2 lower urinary tract symptoms: bladder spasm, urinary frequency, urgency, dysuria and haematuria. Critically, no grade 3 or 4 treatment-related adverse events, treatment-related deaths or treatment-related discontinuations were reported. The median time to resolution of adverse events was 1 day (IQR 0-7). Only two grade 2 serious treatment-related adverse events (non-infective cystitis and bladder haemorrhage) were observed.

Implications for Clinical Practice

1. The bladder preservation window is widening

The fact that 81% of patients were able to keep their bladder at month 24 is a meaningful gain in this population. More importantly, the final pathology was non-muscle-invasive disease or pT0 in 15 of the 18 patients (83%) who proceeded to cystectomy for recurrence or progression, showing that the treatment does not close the window for salvage surgery. This finding is central to the oncological safety of a bladder-sparing approach.

2. Efficacy in a heavily pre-treated, real-world population

A complete response rate of 75.5% achieved in a cohort that had received a median of 12 BCG instillations, with some patients also treated with gemcitabine-docetaxel or systemic pembrolizumab, strengthens the applicability of the results to the patient profile encountered in daily practice.

3. Feasibility: a regimen requiring no operating room or anaesthesia

Cretostimogene can be administered in the outpatient setting in line with existing AUA/SUNA intravesical administration policies, without prophylactic anticholinergics, operating room time, additional cystoscopy or anaesthesia. This operational simplicity is a decisive advantage that facilitates integration into both academic and community urology practice.

4. Position in the treatment algorithm

The BCG-unresponsive NMIBC space is becoming crowded rapidly: pembrolizumab, nadofaragene firadenovec, nogapendekin alfa inbakicept and the recently approved durvalumab-BCG combination all occupy this space. The distinguishing feature of cretostimogene is that it combines a high complete response rate with long-lasting durability and a toxicity profile confined almost entirely to grade 1-2 events. Although the agent has FDA Fast Track and Breakthrough Therapy designations, it has not yet received FDA approval.

5. Ongoing research programme

The role of cretostimogene across the bladder cancer spectrum continues to be evaluated in PIVOT-006 (NCT06111235) in intermediate-risk NMIBC and CORE-008 (NCT06567743) in high-risk NMIBC. BOND-003 also continues with additional analyses of response durability.

Conclusion

The Lancet Oncology publication of BOND-003 Cohort C provides high-quality evidence that strengthens the bladder-sparing treatment paradigm in BCG-unresponsive high-risk NMIBC. Taken together, a 75.5% complete response rate, a median duration of response reaching 27.9 months, 81% cystectomy-free survival at 24 months and the absence of grade ≥3 toxicity make cretostimogene a strong candidate option in this challenging patient group.

That said, the single-arm design of the trial, the absence of randomized comparative data and the still immature follow-up should be kept in mind as methodological limitations. Long-term oncological safety and comparative efficacy against other bladder-sparing agents are the key questions that need to be answered in the period ahead.

A note for our patients: This article is an appraisal of the current scientific literature prepared for physicians and interested readers. The treatment described here is still investigational and does not constitute a treatment recommendation. In bladder cancer treatment, every patient's disease stage, prior treatments and general health differ. Always consult your own physician regarding treatment decisions.

References

• Tyson MD, Nam JK, Joshi SS, et al. Intravesical cretostimogene grenadenorepvec oncolytic immunotherapy in high-risk, BCG-unresponsive, non-muscle-invasive bladder cancer with carcinoma in situ (BOND-003 Cohort C): a single-arm, phase 3 trial. Lancet Oncol. 2026;27(8):983-993. doi:10.1016/S1470-2045(26)00194-4 - thelancet.com
• Clarke H. Published BOND-003 data show durable responses with cretostimogene in NMIBC. Urology Times, 28 July 2026. - urologytimes.com
• CG Oncology "CG Oncology Announces Publication of Pivotal Phase 3 BOND-003 Cohort C Study Results in The Lancet Oncology". Press release, 27 July 2026. - ir.cgoncology.com
• BOND-003 trial registration (NCT04452591) - clinicaltrials.gov
• PIVOT-006 trial registration (NCT06111235) - clinicaltrials.gov
• CORE-008 trial registration (NCT06567743) - clinicaltrials.gov