Cretostimogene Grenadenorepvec Shows Efficacy in Papillary-Only, BCG-Unresponsive NMIBC

Intravesical cretostimogene grenadenorepvec (CG0070) led to strong high-grade event-free survival (HG-EFS) rates in patients with BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC) with maintained responses across those with high-grade papillary Ta (HG-Ta) and higher-risk high-grade T1 (HG-T1) disease, according to topline data from cohort P of the phase 3 BOND-003 trial (NCT04452591).1

The findings, which were shared during the 26th Annual Meeting of the Society of Urologic Oncology, showed that at a median follow-up of 6.0 months, the product led to consistent and high HG-EFS rates in those with HG-Ta disease and those with HG-T1 disease. In the former group, the HG-EFS rates at 3, 6, and 9 months were 92.8%, 75.9%, and 75.9%, respectively; in the latter group, these respective rates were 100%, 100%, and 87.5%. No patients underwent radical cystectomy or experienced disease progression to muscle-invasive bladder cancer (MIBC).

“We [also] see consistent and favorable tolerability [with cretostimogene grenadenorepvec], and obviously, long-term follow-up is ongoing and continuing to evolve,” Mark Tyson, MD, MPH, a urologic oncologist at Mayo Clinic, said in a presentation of the data.

What inspired the exploration of cretostimogene grenadenorepvec in patients with BCG-unresponsive, papillary NMIBC?

Cretostimogene grenadenorepvec is an oncolytic immunotherapy with a dual mechanism of action in which viral replication leads to tumor lysis and stimulation of immune response. Tyson underscored that there remains a substantive unmet need for effective, tolerable, and bladder-sparing options in BCG-unresponsive, papillary-only NMIBC.

The approaches that are currently approved by the FDA for those with high-risk, BCG-unresponsive NMIBC are for those with carcinoma in situ (CIS) ± papillary disease. These options include pembrolizumab (Keytruda), nadofaragene firadenovec-vncg (Adstiladrin), N-803 (Anktiva) plus BCG, and TAR-200 (gemcitabine intravesical system; Inlexzo).

Tyson shared that benchmark data indicated that with pembrolizumab, disease-free survival (DFS)/high-grade recurrence-free survival (HG-RFS) rates at 3, 6, 9, 12, and 24 months were 87.7% (95% CI, 80.7%-92.3%), 53.1% (95% CI, 44.1%-61.2%), not reported, 43.5% (95% CI, 34.9%-51.9%), and 34.9% (95% CI, 26.4%-43.4%). With nadofaragene firadenovec, these respective rates were 72.9% (95% CI, 58.2%-84.7%), 62.5% (95% CI, 47.4%-76.0%), 58.3% (95% CI, 43.2%-72.4%), 43.8% (95% CI, 29.5%-58.8%), and 33.3% (95% CI, 20.4%-48.4%). With TAR-200, these respective rates were not reported, 85.3% (95% CI, 71.6%-92.7%), 81.1% (95% CI, 66.7%-89.7%), 70.2% (95% CI, 51.6%-82.8%), and not reported. Lastly, with N-803 paired with BCG, the DFS/HG-RFS rates at 12 and 24 months were 55.4% (95% CI, 42.0%-66.8%) and 48.3% (95% CI, 34.5%-60.7%), respectively.

What BOND-003 data were previously reported?

Cohort C (n = 110) included patients with pathologically confirmed BCG-unresponsive high-risk NMIBC with CIS ± papillary disease who were at least 18 years of age and had an ECOG performance status ranging from 0 to 2. The primary end point in this group was complete response (CR) at any time, and secondary end points included duration of response, cystectomy-free survival (CFS), recurrence-free survival (RFS), and progression-free survival (PFS).

Prior data from this cohort indicated that cretostimogene grenadenorepvec elicited an overall CR rate of 75.5% (95% CI, 66.3%-83.2%);2 CR landmark rates at 12 and 24 months were 46.4% (95% CI, 36.9%-56.1%) and 41.8% (95% CI, 32.5%-51.6%), respectively; 12- and 24-month CR rates by Kaplan-Meier estimates were 50.7% (95% CI, 40.9%-59.8%) and 42.4% (95% CI, 32.7%-51.7%).1

Moreover, most patients had not progressed to MIBC (96.4%), and 83.6% did not undergo radical cystectomy after recurrence or progression. Of the 18 patients who did have radical cystectomy after recurrence or progression, 83.3% had T0 or NMIBC.

Who were the patients enrolled in cohort P of the trial, and what was examined?

Cohort P enrolled patients aged 18 years or older who had pathologically confirmed high-risk, BCG-unresponsive papillary only (HG-Ta/T1) NMIBC whose disease was completely resected prior to treatment. The primary end point in this cohort was HG-EFS, and secondary end points include RFS, PFS, CFS, and cancer-specific survival.

The patient demographics and baseline characteristics for the patients who were included in the safety dataset (n = 56) showed that the median age was 74.0 years (range, 45-87); 78.6% were male, and 96.4% were in the United States. In terms of age, 23.2% of patients were under 65 years, 32.1% were at least 65 years but younger than 75 years, and 44.6% were 75 years or older. With regard to ECOG performance status, 85.7% had a status of 0, and 14.3% had a status of 1. Moreover, at the time of study entry, 58.9% of patients had HG-Ta disease, and 41.1% had HG-T1 disease. The median number of prior instillations of BCG was 9.0 (range, 5-21).

What was learned about the toxicity profile of cretostimogene grenadenorepvec?

Any-grade treatment-related adverse effects (TRAEs) occurred in 71.4% of patients, although no cases were grade 3 or higher, serious, or proved fatal. Notably, TRAEs did not lead to any dose delays, missed doses, or discontinuation of cretostimogene grenadenorepvec. Most patients (98.2%) received all treatments per protocol.

The most common any-grade TRAEs experienced by more than 10% of patients who received cretostimogene grenadenorepvec were bladder spasm (46.4%), dysuria (39.3%), pollakiuria (25.0%), and urgency (19.6%).

What’s next for cretostimogene grenadenorepvec?

In November 2025, CG Oncology, the developer, announced that they initiated their rolling biologics license application submission for cretostimogene grenadenorepvec; they expect this to be completed next year.3 Previously, in December 2023, the FDA had awarded fast track and breakthrough therapy designations to cretostimogene grenadenorepvec for use in high-risk, BCG-unresponsive NMIBC with CIS with or without Ta or T1 tumors.4

Disclosures: No conflicts of interest were listed.

References

1. Tyson M. Topline results from BOND-003 cohort P-a multi-national, single-arm study of intravesical cretostimogene grenadenorepvec for treatment of high-risk, papillary only (HG Ta/T1), BCG-unresponsive NMIBC. Presented at: Society of Urologic Oncology Annual Meeting; December 2-5, 2025; Phoenix, Arizona.
2. Tyson M. BOND-003 cohort C- a phase-3, single-arm study of intravesical cretostimogene grenadenorepvec for high-risk BCG-unresponsive NMIBC with CIS. Presented at: American Urological Association Annual Congress; April 26-29, 2025; Las Vegas, NV. P2s.
3. CG Oncology reports third quarter 2025 financial results and provides business updates. News release. CG Oncology, Inc. November 14, 2025. Accessed December 5, 2025. https://ir.cgoncology.com/news-releases/news-release-details/cg-oncology-reports-third-quarter-2025-financial-results-and
4. CG Oncology receives both FDA fast track and breakthrough therapy designation for cretostimogene grenadenorepvec in high-risk BCG-unresponsive non-muscle invasive bladder cancer. News release. CG Oncology, Inc. December 5, 2023. Accessed December 5, 2025. https://cgoncology.com/cg-oncology-receives-both-fda-fast-track-and-breakthrough-therapy-designation-for-cretostimogene-grenadenorepvec-in-high-risk-bcg-unresponsive-non-muscle-invasive-bladder-cancer/