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.
“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.
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
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.
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.