Updated results from the phase 2 CORE1 trial shared during the 2022 Society for Immunotherapy of Cancer (SITC) Annual Meeting continued to show promising anti-tumor activity for the combination of the novel oncolytic immunotherapy CG0070 and pembrolizumab (Keytruda) in patients with BGG-unresponsive non–muscle-invasive bladder cancer (NMIBC).”1
At the initial 3-month timepoint, 28 (88%) of 32 evaluable patients achieved a complete response (CR). Among patients evaluable for CR at longer timepoints, 88% (23/26), 86% (18/21), and 73% (11/15) maintained a CR through 6, 9, and 12 months respectively.
Safety data for the trial, which were reported previously at the 2022 AACR Annual meeting, showed that there were no grade 3 to 5 adverse events (AEs) and no new safety signals for the 2 treatments compared with prior monotherapy studies of each agent.2
Any grade AEs in CORE1 included pollakiuria (n = 6), bladder spasm (n = 4), dysuria (n = 4), fatigue (n = 4), nocturia (n = 3), chills (n = 2), hematuria (n = 2), micturition urgency (n = 2), polyuria (n = 2), as well as arthralgia, autoimmune thyroiditis, blood thyroid stimulating hormone increased, device leakage, diarrhea, headache, hot flush, hyperglycemia, hypothyroidism, influenza-like illness, joint stiffness, malaise, musculoskeletal stiffness, myalgia, penile hemorrhage, pruritis, pyrexia, urinary tract infection, and urinary tract pain (n = 1 each).
CG0070 is a selective oncolytic adenovirus that has been engineered to preferentially replicate in tumor cells. As an oncolytic immunotherapy, CG0070 has a 2-pronged attack or mechanism of action: It infects the tumor cell, replicates, and kills the tumor cells and, in return, infects other tumor cells along the line; and it has a mechanism of action stimulating the anti-tumor immune response with the GM-CSF cassette, priming and activating the T cell for tumor self-destruction.
“There is a critical unmet need for efficacious bladder-sparing therapies for patients with BCG-unresponsive bladder cancer,” Roger Li, MD, lead study investigator and urologic oncologist at Moffitt Cancer Center, stated in a news release. “CG0070 has continued to show very promising results, more than doubling CR rates previously seen with immune checkpoint inhibitors. With a unique dual-mechanism of action that first engages an immune response and then amplifies that response with immune checkpoint blockade, this novel combination of CG0070 with pembrolizumab could potentially change the outlook for patients with BCG-unresponsive bladder cancer.”
The open-label, single-arm phase 2 CORE1 trial has completed its targeted enrollment of 35 patients. Key entry criteria included those with NMIBC unresponsive to BCG disease; 5+2 BCG minimum prior exposure; relapse with cisplatin within the last 12 months of BCG treatment; CIS with or without Ta/T1 tissue diagnosis within 10 weeks of first study treatment; were ineligible or refused cystectomy; and could undergo mandatory bladder mapping at 12 months and central pathology review at screening and for response assessment.
Reinduction for non-progressing patients at month 3 was allowed. Patients were excluded if they previously received pembrolizumab or other anti–PD-(L)1 therapy; had ongoing, active gross hematuria; and prior adenovirus serotype 5 therapeutic exposure.
The primary end point of the trial was CR at 12 months, and secondary end points included safety, CR at any time, progression-free survival, cystectomy-free survival, duration of response, and immune correlates on all patients.
CG0070 is currently being evaluated as a monotherapy in the open-label, phase 3 BOND3 trial, with a target enrollment of 110 patients with NMIBC. The primary end point is CR at any time.
1. CG Oncology Presents New Phase 2 Data with CG0070 in Combination with KEYTRUDA® (pembrolizumab) in Non-Muscle Invasive Bladder Cancer Unresponsive to Bacillus Calmette-Guérin. Published online November 10, 2022. Accessed November 15, 2022. https://www.cgoncology.com/news/press-releases/111022/
2. Li R, Steinberg G, Shah P, 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: AACR Annual Meeting 2022; April 8-13, 2022; New Orleans, Louisiana. Abstract CT036.