AUA 2023: CORE1: Phase 2 Single Arm Study of CG0070 Combined with Pembrolizumab in Patients with Non-Muscle Invasive Bladder Cancer Unresponsive to Bacillus Calmette-Guerin (BCG)

( The 2023 American Urological Association (AUA) annual meeting held in Chicago, IL between April 28 and May 1st, 2023, was host to a non-invasive bladder cancer podium session. Dr. Roger Li presented the results of CORE1, a phase 2 single arm study of CG0070 combined with pembrolizumab in patients with non-muscle invasive bladder cancer unresponsive to Bacillus Calmette-Guerin (BCG).

Cretostimogene Grenadenorepvec (CG0070) is a cancer-selective oncolytic adenovirus engineered to preferentially replicate in tumor cells. The E2F Promoter along with GM-CSF transgene are inserted into wild-type adenovirus backbone, with the function of each gene/protein summarized in the table below:
CG0070 monotherapy has previously been evaluated in a phase 1 trial (V0046) of 35 patients with high-risk, BCG-failure NMIBC (CIS-containing or papillary). CG0070 demonstrated a complete response rate of 46% at 3 months and met the safety/efficacy outcomes, with the target dose and schedule identified for a subsequent phase 2 study.


Next, CG0070 monotherapy was evaluated in an open label, phase 2 trial (BOND-002) of 46 patients with BCG-failure NMIBC (CIS containing). A CR at any time was achieved in 30/46 patients (65%), with durable CRs of 44% and 28% at 6 and 12 months, respectively.3_phase_2_cretostimogene.png
Based on these promising results, the phase 3 BOND-003 trial will evaluate CG0070 monotherapy for patients with high-risk, BCG-unresponsive NMIBC (CIS-containing).
Given the mechanism of action of CG0070, as illustrated in the figure below, it has been hypothesized that CG0070 and pembrolizumab (PD-1 inhibitor) may have synergistic mechanisms of action.5_cretostimogene_mechanism_of_action.png
As such, CORE1 was designed as an open label, single arm Phase 2 trial evaluating the combination of CG0070 plus pembrolizumab in 35 patients with high-risk, BCG-unresponsive NMIBC (CIS-containing). All patients received CG0070 induction weekly (1x1012 vp/mL) for 6 weeks, followed by a second induction course weekly for 3 weeks in responders and 6 weeks in non-responders. All responders subsequently received a maintenance course weekly for 3 weeks. Patients concurrently received pembrolizumab every 6 weeks (as opposed to the usual 3 weeks) at a dose of 400 mg through year 2. The study endpoints were CR at any time and 12 months (duration of response).6_cretostimogene_and_pembro.png
Baseline patient characteristics are summarized below. The median number of prior BCG instillations was 12 (range: 9 – 30). 60% had persistent high-risk NMIBC, with the remaining 40% having recurrent high-risk NMIBC. Of note, 80% of patients had pure CIS.7_CORE_001_characteristics.png
The swimmer’s plot for the study subjects is demonstrated below. Impressively, an overall CR rate of 85% was observed. This was longitudinally maintained with 6-, 9-, and 12-month CR rates of 82%, 81%, and 68%, respectively.8_CORE_1_results.png
With regards to adverse events:

  • Predominantly transient, grade 1-2 local GU AEs
  • Grade 3 AEs were observed in 4 patients (11%)
  • No grade 4-5 AEs were observed
  • AE profile was generally consistent with prior studies of each agent alone
  • No clear evidence of additive/synergistic toxicity

Dr. Li concluded as follows:

  • Monotherapy activity of CG0070 in NMIBC after BCG failure has been established in the past 2 studies of CG0070: V0046 and BOND-002
  • The combination of CG0070 and pembrolizumab appears to be highly active in BCG-unresponsive NMIBC based on preliminary results of the CORE-001 study
  • Studies of CG alone (Phase 3 BOND-003, ongoing study) and in combination with checkpoint inhibitor therapy (Phase 3 PIVOT-001, planned study) will further elucidate the potential role of CG0070-based therapy for BCG-unresponsive NMIBC
Presented by: Roger Li, MD, Assistant Professor, Urologic Oncology, Moffitt Cancer Center, Tampa, FL

Written by: Rashid K. Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2023 American Urological Association (AUA) Annual Meeting, Chicago, IL, April 27 – May 1, 2023

  1. Burke J, 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.
  2. Packiam, 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. 
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Gene Therapy and Pembrolizumab in BCG-Unresponsive CIS-Containing Population: Updated Results, Efficacy, and Correlative Studies - Roger Li