Oncolytic Virus Shows High CR Rates in NMIBC

Mark D. Tyson, II, MD, MPH

The targeted oncolytic immunotherapy cretostimogene grenadenorepvec induced complete responses in over three-fourths of patients with high-risk BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC), according to findings from the phase 3 BOND-003 trial (NCT04452591) presented at the 24th Annual Meeting of the Society of Urologic Oncology (SUO).¹

“Based on central review, 75.7% [95% CI, 63%85%] of patients reached a complete response at any time point. The responses were durable, with 74.4% of the complete responses lasting for at least 6 months,” Mark D. Tyson, II, MD, MPH, a urologic oncologist at Mayo Clinic in Phoenix, Arizona, said when presenting the data.

To enroll, patients had to have pathologically confirmed high-risk NMIBC with carcinoma in situ (CIS) with or without Ta/T1 papillary disease that is unresponsive to BCG treatment, have an ECOG performance status of 0 to 2, and not be eligible for or refuse to receive a radical cystectomy.

Overall, 116 patients with BCG-unresponsive high-risk NMIBC have been enrolled, and the efficacy data presented at the SUO meeting were from the interim analysis of the first 66 patients at a cutoff date of October 5, 2023.

Of 66 patients in the trial, 50 were male. The median patient age was 73 years (range, 49-90). Fifty-three patients (80%) had an ECOG performance status of 0, and 13 patients (20%) had an ECOG performance status of 1. Regarding staging, 2 patients had CIS with T1, 10 patients had CIS with high-grade Ta, and 54 patients had CIS.

In the study design, the oncolytic immunotherapy is administered beginning with a weekly induction regimen lasting 6 weeks. This is followed by 3 weekly maintenance instillations at months 3, 6, 9, 12, and 18. Patients who continue to have high-grade disease at 3 months are eligible to receive a reinduction regimen of 6 weeks of weekly cretostimogene grenadenorepvec. Notably, data from the interim analysis showed that 31% of patients who did not respond to their first course of treatment were able to be salvaged with reinduction.

The primary end point of the trial is the rate of complete responses achieved throughout the study. Secondary end points include the complete response rate at 12 months, duration of response, progression-free survival, cystectomy-free survival, and safety. The complete response rate at 3 months was 68.2% (n = 45), and the complete response rate at 6 months was 63.6% (n = 42).

In the safety population (n=112) most adverse events (AEs) were grade 1/2. The most common treatment-related AEs (TRAEs) were bladder spasm (20.5%), pollakiuria (16.1%), and dysuria (14.3%). Two patients (1.8%) experienced grade 2 serious TRAEs, no patients had grade 3 or higher TRAEs, and there were no treatment- related discontinuations or patient deaths.

Next steps for BOND-003 involve treatment extension and the addition of a papillary-only cohort. The phase 3 PIVOT-006 study (NCT06111235) is also launching. This trial is comparing transurethral resection of bladder tumor (TURBT) followed by adjuvant cretostimogene grenadenorepvec vs TURBT followed by observation.

Tyson noted that cretostimogene grenadenorepvec has received FDA fast track designation for the treatment of patients with BCG- unresponsive CIS with or without Ta/T1 papillary disease. Commenting on the findings in a news release, Trinity J. Bivalacqua, MD, PhD, professor of urology and director of urologic oncology at the Perelman Center for Advanced Medicine, University of Pennsylvania, said, “The positive BOND-003 initial results demonstrate the impact of cretostimogene in BCG- unresponsive disease patients as a promising new monotherapy, which may lead to profoundly meaningful nonsurgical outcomes for those with recurrent bladder cancer. NMIBC has been a difficult disease to treat, and patients have often had no options except surgical removal of the bladder.”²

REFERENCES

1. Tyson M, Uchio E, Jong-Kil N, et al. First results from BOND-003, a phase 3 study of intravesical cretostimogene grenadenorepvec monotherapy for patients with high-risk BCG-unresponsive non-muscle invasive bladder cancer. Presented at: 24th Annual Meeting of the Society of Urologic Oncology. November 28-December 1, 2023; Washington, DC. LBA3396.

2. Cretostimogene grenadenorepvec monotherapy first results show 75.7% complete response rate at any time in patients with high-risk BCG-unresponsive non-muscle-invasive bladder cancer. News release. CG Oncology. November 30, 2023. Accessed November 30, 2023. http://tinyurl.com/3av3thh9