A phase 1/2 study is launching to explore the combination of PD-1 inhibitor nivolumab (Opdivo) and the novel oncolytic immunotherapy CG0070 in patients with metastatic urothelial carcinoma.1
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.”
The phase 1/2 trial is a collaboration between CG Oncology and nivolumab developer Bristol Myers Squibb.
“We are excited to initiate this important clinical trial with our lead oncolytic immunotherapy, CG0070, in combination with Opdivo in metastatic urothelial cancer,” Arthur Kuan, CEO of CG Oncology, stated in a press release. “The clinical results to date for CG0070 make it a potential promising agent in bladder cancer and other tumor types, as monotherapy or in combination with immune checkpoint inhibitors.”
Nivolumab currently has multiple FDA-approved indications for the treatment of patients with urothelial carcinoma, while CG0070 remains in clinical development.
Following promising data from phase 1 and 2 studies of the agent, CG0070 is now being evaluated as a single agent in the phase 3 BOND-003 trial (NCT04452591) in patients with BCG-unresponsive non–muscle-invasive bladder cancer.
In an abstract presented at the 2020 Society of Urologic Oncology annual meeting,2 investigators outlined the BOND-003 trial. The study is a single-arm trial in which 110 patients with BCG-unresponsive NMIBC will be treated with CG0070 weekly x 6 followed by weekly x 3 maintenance indications at 3, 6, 9, 12, and 18 months. Patients will be enrolled across the US and Asia-Pacific regions.
The study’s primary end point is complete response (CR) at any time. Secondary end points include CR at 12 months, duration of response, progression-free survival, cystectomy-free survival, and safety.
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
In December 2020, CG Oncology reported that the first patient had been dosed in a phase 2 clinical trial evaluating CG0070 in combination with pembrolizumab (Keytruda) for the treatment of BCG-unresponsive NMIBC.5
1. 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.
2. Uchio E, Lamm DL, Shore N, et al. Phase 3 study of CG0070 in patients with non-muscular invasive bladder cancer (NMIBC) unresponsive to bacillus-Calmette-Guerin (BCG). Paper presented at: 2020 Society of Urologic Oncology annual Meeting. December 3-5, 2020; virtual. Accessed January 22, 2021. https://bit.ly/39cQPHz.
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
5. CG Oncology announces first patient dosed in phase 2 clinical trial of CG0070, an oncolytic immunotherapy, in combination with Keytruda (pembrolizumab) for non-muscle-invasive bladder cancer unresponsive to bacillus Calmette-Guerin. News release. CG Oncology. December 9, 2020. Accessed January 22, 2021. http://bit.ly/2Y5Kh76.