Introduction:

CG0070 is a serotype 5 adenovirus engineered to express GM-CSF and replicate in cells with mutated or deficient RB.  The monotherapy response rates (RR) of approximately 45% have been observed in NMIBC after BCG failure (Burke JM 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;188:2391–7; Packiam VT 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):440–7).  This single arm phase 3 study was launched to confirm the clinical activity of monotherapy CG0070 in patients with NMIBC unresponsive to BCG.

Methods:

110 patients with BCG-unresponsive CIS with or without concurrent Ta or T1 disease will be treated with intravesical (IVE) CG0070 at a dose of 1x10¹² vp.  CG0070 will be administered weekly x 6 as induction followed by weekly x 3 maintenance instillations at months 3, 6, 9, 12, and 18. Patients with persistent CIS or HG Ta at 3 months (m) may receive re-induction with weekly x 6 CG0070.  Assessment of response will include q 3 m cystoscopy with biopsy of areas suspicious for disease, urine cytology, CTU/MRU, and mandatory bladder mapping at 12 m.  Detection of high grade disease within the bladder will be enumerated as recurrence or non-response. 

Results:

The primary endpoint of the study is CR at anytime on study.  Secondary endpoints will include CR at 12 m, duration of response, progression free survival, cystecomy free survival and safety.  Correlative assessments will include  changes in the tumor immune microenvironment, systemic immune induction as reflected in the peripheral blood and urine, as well as viral replication and transgene expression.  Baseline expression of coxsackie adenovirus receptor, E2F transcription factor as well as anti-adenovirus antibody titer will be correlated with tumor response. 

Conclusion:

Study enrollment across the US and Asia Pacific regions is planned to be completed over the next 24 m.  An update on trial enrollment and preliminary data will be presented at the time of presentation. 

Funding: N/A