AUA 2022: CORE1: Phase 2, Single Arm Study of CG0070 Combined with Pembrolizumab in Patients with Non Muscle Invasive Bladder Cancer Unresponsive to BCG

( The 2022 Annual Meeting of the American Urological Association was host to a moderated poster session for non-invasive bladder cancer. Dr. Roger Li presented the interim analysis of the CORE1: Phase 2, single arm study evaluating the combination of CG0070 with IV pembrolizumab in BCG unresponsive CIS patients.

CG0070 is an adenovirus serotype 5-based oncolytic vaccine engineered to express GM-CSF and replicate selectively in tumor cells with a mutated/deficient retinoblastoma (RB) gene. The mechanism of action of CG0070 is cell lysis and immunogenic cell death, augmented in the presence of GM-CSF. High risk NMIBC patients previously treated with BCG have an overall CR rate of 62% and a 12-month CR rate of 29%. Intravenous pembrolizumab has recently been approved by the FDA on the basis of the Keynote-057 trial that demonstrated an overall CR of 41% at 3 months with a 12-month CR rate of ~20% in BCG unresponsive CIS +/- papillary tumors.1

This phase II trial has a target study population of 35 patients with BCG-unresponsive CIS +/- papillary tumors that will be treated with intravesical CCG0070 (1x1012 vp) in combination with pembrolizumab 400 mg IV q6 weeks. The dosing regimen for CG0070 will be weekly for 6 weeks as induction followed by 3 weekly maintenance instillations at 3, 6, 9, 12, and 18 months. Patients with persistent CIS or HG Ta at 3 months may be eligible to receive reinduction with 6 weekly doses of CG0070. Patients will receive pembrolizumab for up to 24 months. Disease recurrence will be assessed using q 3-month cystoscopy with biopsy of areas suspicious for disease, urine cytology, cross sectional imaging with CT or MR urogram, and mandatory bladder mapping biopsies at 12 months. Disease recurrence will be defined as any high-grade recurrence.

The primary study endpoint is 12-month CR. Secondary endpoints will be CR at any time, PFS, response duration, cystectomy-free survival, and the adverse event profile. Tumor immune microenvironment, systemic immune induction, viral replication, and transgene expression will be assessed. Baseline expression of PD-L1, coxsackie adenovirus receptor, E2F transcription factor as well as anti-adenovirus serotype 5 Ab titer will be correlated with tumor response.

At the time of abstract submission, nine patients had been enrolled and followed for 3 months. All nine patients had a CR. 6 months follow up was attained by six patients and 9 months follow up by 3 patients. No patient has recurred yet. Treatment-related adverse events have been limited to transient grade 1-2 urinary frequency. No treatment-related grade 3 or higher AE or SAE have been observed.
The authors concluded that the combination of CG0070 and pembrolizumab is well-tolerated with encouraging early efficacy data.


Presented By: Roger Li, MD, Assistant Professor, Urologic Oncology, Moffitt Cancer Center, Tampa, FL

Written By: Rashid Sayyid, MD, MSc – Urology Chief Resident, Augusta University/Medical College of Georgia, @rksayyid on Twitter during the 2022 American Urological Association (AUA) Annual Meeting, New Orleans, LA, Fri, May 13 – Mon, May 16, 2022.

  1. Balar AV, Kamat AM, Kulkarni GS, et al. Pembrolizumab monotherapy for the treatment of high-risk non-muscle-invasive bladder cancer unresponsive to BCG (KEYNOTE-057): an open-label, single-arm, multicentre, phase 2 study. Lancet Oncol. 201;22(7):919-930.