CG0070 Plus Pembrolizumab Shows Early Tolerability and Activity in BCG-Unresponsive Non–Muscle Invasive Bladder Cancer

The combination of CG0070 and pembrolizumab (Keytruda) was well tolerated and demonstrated early signals of activity in patients with Bacille Calmette-Guérin (BCG)-unresponsive non–muscle invasive bladder cancer (NMIBC), according to preliminary findings from the phase 2 CORE1 trial (NCT04387461) that were presented during the 2021 SITC Annual Meeting.¹

The results showed that all 7 (100%) patients evaluable for efficacy achieved a complete response (CR) at 3 months. Additionally, 6 of the 7 patients maintained their CR through 6 months and 2 patients did at 9 months.

“We are excited to announce these preliminary results toward CG0070’s safety, tolerability, and clinical efficacy in patients with bladder cancer unresponsive to BCG who have limited treatment options,” said Arthur Kuan, chief executive officer of CG Oncology, in a press release.² “We hope to see continued responses as the study progresses, as CG0070’s dual mechanism of action has shown to be highly effective in this difficult-to-treat patient population.”

CG0070, an oncolytic intravesical vaccine, is a serotype 5 adenovirus engineered to express GM-CSF and replicate in RB-mutated or -deficient tumor cells. CG0070 operates through direct cell lysis with immune-mediated cell death, which is enhanced by GM-CSF.

Findings from a phase 1 and phase 2 study demonstrated a CR rate of approximately 62% and a 12-month CR rate of 29% in patients with high-risk BCG-pretreated NMIBC.

On January 8, 2020, the FDA approved pembrolizumab for patients with BCG-unresponsive, high-risk NMIBC with carcinoma in situ with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.³

The approval was based on data from the phase 2 KEYNOTE-057 trial (NCT02625961), in which the PD-1 inhibitor elicited a CR rate of 41% and a 12-month CR rate of approximately 20%.

CORE1 was designed to evaluate the potential synergy of CG0070 and pembrolizumab in BCG-unresponsive NMIBC.

The study included 35 patients with BCG-unresponsive carcinoma in situ with or without concurrent Ta or T1 disease.

Patients were treated with CG0070 at a dose of 1 x 1012 vp plus 400 mg of intravenous pembrolizumab every 6 weeks. CG0070 was given every week for 6 cycles followed by an additional 3 cycles of maintenance therapy at months 3, 6, 9, 12, and 18.

Patients with persistent carcinoma in situ or high-grade Ta disease at 3 months were allowed to receive re-induction with weekly CG0070 for 6 cycles. Pembrolizumab was administered for up to 24 months.

Response was evaluated with cystoscopy with a biopsy of areas that were suspicious for disease every 6 months, urine cytology, CT urography/magnetic resonance urography, and required bladder mapping biopsies at 12 months.

The primary end point of the study is the 12-month CR rate. Secondary end points include the CR at any time, progression-free survival, duration of response, cystectomy-free survival, and safety of the combination.

Exploratory endpoints include the assessment of immune induction in the tumor, blood and urine, viral infection, replication, and transgene expression, baseline PD-L1, CAR, E2F transcription factor and anti-Ad5 antibody titers vs response.

Additional safety findings demonstrated that treatment-related adverse effects (TRAEs) included grade 1/2 local genitourinary symptoms and immune-related AEs, including urinary frequency (n = 4), bladder spasm (n = 2), fatigue (n = 2), chills, autoimmune thyroiditis, blood discharge, dysuria, and flu-like symptoms (n = 1 each).

No grade 3 or higher TRAE or serious AEs were reported.

“These preliminary results are exciting,” said Roger Li, MD, lead study investigator and urologic oncologist at Moffitt Cancer Center. “If similar trends hold moving forward, we may have a game changer to combat BCG-unresponsive bladder cancer for patients with significant unmet medical need.”

References

1. Li R, Lamm D, Uchio E, et al. CORE1: phase 2, single arm study of CG0070 combined with pembrolizumab in patients with non-muscle invasive bladder cancer (NMIBC) unresponsive to Bacillus Calmette-Guerin (BCG). Presented at: 2021 SITC Annual Meeting; November 10-14, 2021; Washington DC. Abstract 955.
2. CG Oncology presents preliminary phase 2 data with CG0070 in combination with KEYTRUDA® (pembrolizumab) in non-muscle-invasive bladder cancer unresponsive to bacillus calmette-guerin. News release. CG Oncology, Inc. November 13, 2021. Accessed November 24, 2021. https://bwnews.pr/30U0Tn4
3. FDA approves pembrolizumab for BCG-unresponsive, high-risk non-muscle invasive bladder cancer. News release. FDA. January 8, 2020. Accessed November 24, 2021.https://bit.ly/2tFigXZ