Phase 3 trial will evaluate oncolytic immunotherapy for BCG-unresponsive NMIBC

Researchers will evaluate the investigational intravesical BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC) treatment CG0070 in a phase 3 trial following promising data from phase 1 and 2 studies of the agent.

According to CG Oncology, which is developing the treatment, 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.”¹

Discussing the agent, investigator Edward Uchio, MD, clinical professor of urology at the University of California, Irvine, highlighted CG0070’s intravesical nature, as urologists are already familiar with administering intravesical treatments such as BCG.

“[Urologists are] very comfortable giving agents in the bladder, so [CG0070] really fits in line with what we give,” Uchio said.

In an abstract presented at the 2020 Society of Urologic Oncology annual meeting,² investigators outlined the BOND-003 trial (NCT04452591) of CG0070. BOND-003 is a single-arm study 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.

“We anticipate we will complete enrollment globally over the next year and a half, and then publish the early data probably within 6 to 12 months thereafter,” study investigator James Burke, MD, chief medical officer of CG Oncology, said in December.

The study’s primary end point will be complete response 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 antibladder 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 also 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.¹

References

1. 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

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