Pembrolizumab plus novel oncolytic immunotherapy shows early promise in NMIBC

The combination of pembrolizumab (Keytruda) and the novel oncolytic immunotherapy CG0070 showed promising early efficacy in patients with BCG-unresponsive non–muscle invasive bladder cancer (NMIBC), according to preliminary data from the phase 2 CORE1 study.¹

Results presented at the 2021 Society for Immunotherapy of Cancer Annual Meeting showed that all 9 efficacy-evaluable patients achieved a complete response (CR) at the initial 3-month analysis. Further, all patients reaching the 6-month timepoint (n = 6)—as well as all patients who reached the 9-month timepoint (n = 3)—maintained their response.

All treatment-related adverse events (TRAEs) were grade 1/2 and short-lived. The most common included urinary frequency, bladder spasm, fatigue, chills, autoimmune thyroiditis, blood discharge, dysuria, and flu-like symptoms. Thus far, investigators have not observed any grade ≥3 TRAEs or severe AEs.

Roger Li, MD

“These preliminary results are exciting,” Roger Li, MD, lead study investigator and Urologic Oncologist at Moffitt Cancer Center, stated in a news release. “If similar trends hold moving forward, we may have a game changer to combat BCG-unresponsive bladder cancer for patients with significant unmet medical need.”

According to developer CG Oncology, CG0070 is a “selective oncolytic immunotherapy based on a modified adenovirus type 5 backbone that contains a cancer-selective promoter and a GM-CSF transgene, destroys bladder tumor cells through their defective retinoblastoma (Rb) pathway.”²

Overall, the CORE1 trial (NCT04387461) aims to enroll 37 patients with NMIBC with carcinoma in situ (CIS) with or without Ta/T1 papillary disease. Patients must be unresponsive to BCG therapy, have an ECOG performance status of 0 to 1, and be ineligible for or refuse radical cystectomy.

The primary outcome measure is CR, with secondary outcome measures including safety, duration of response, overall survival, and progression-free survival. The estimated primary completion date is December 2021.

Prior CG0070 research

CG0070 was previously evaluated in the V-0046 phase 1 study (NCT00109655) and BOND2 phase 2 study (NCT02365818). V-0046 evaluated 35 patients treated with CG0070. The agent demonstrated anti–bladder cancer activity, with the most common adverse events consisting of grade 1-2 bladder toxicities.³ The BOND2 trial evaluated 65 patients, with a 62% complete response rate at any time, with complete response maintained in 46% at 12 months.⁴

Additional CG0070 studies

Other ongoing trials are also exploring CG0070, including the phase 3 BOND-003 trial (NCT04452591) examining the oncolytic immunotherapy as a single agent in patients with BCG-unresponsive non–muscle-invasive bladder cancer. Additionally, a phase 1/2 study is exploring the combination of nivolumab (Opdivo) and CG0070 in patients with metastatic urothelial carcinoma.

References

1. CG Oncology Presents Preliminary Phase 2 Data with CG0070 in Combination with KEYTRUDA® (pembrolizumab) in Non-Muscle-Invasive Bladder Cancer Unresponsive to Bacillus Calmette-Guerin. Published online November 13, 2021. Accessed November 15, 2021. https://bit.ly/3Cjjk1e.

2. CG Oncology Announces Clinical Trial Collaboration with Bristol Myers Squibb to Evaluate Oncolytic Immunotherapy CG0070 in Combination with OPDIVO® (nivolumab) in Metastatic Urothelial Cancer. Published online September 9, 2021. Accessed September 9, 2021. https://bwnews.pr/2YwLI1J.

3. Burke JM, Lamm DL, Meng MV, et al. A first in human phase 1 study of CG0070, a GM-CSF expressing oncolytic adenovirus, for the treatment of nonmuscle invasive bladder cancer. J Urol. 2012;188(6):2391-2397. doi:10.1016/j.juro.2012.07.097.

4. Packiam VT, Lamm DL, Barocas DA, et al. An open label, single-arm, phase II multicenter study of the safety and efficacy of CG0070 oncolytic vector regimen in patients with BCG-unresponsive non-muscle-invasive bladder cancer: Interim results. Urol Oncol. 2018;36(10):440-447. doi:10.1016/j.urolonc.2017.07.005.