The phase 3 BOND-003 study (NCT04452591) evaluating cretostimogene grenadenorepvec (formerly, CG0070) had completed enrollment of patients with high-risk non-muscle invasive bladder cancer (NMIBC) unresponsive to Bacillus Calmette-Guerin (BCG). Subsequently, the result of the phase 3 BOND-003 study was announced during Society of Urologic Oncology Annual Meeting (SUOA) in December 2023. The result of the phase 3 showed very good efficacy with little side effects which led to receiving FDA Fast Track Designation for the treatment of patients with BCG-unresponsive CIS with or without Ta/T1 papillary disease.
Cretostimogene grenadenorepvec (CG007) belongs to oncolytic virus technology as bellasmith posted. Oncolytic virus uses virus such as common cold virus but edit virus DNA or RNA and remove the gene which causes sickness, then edit DNA or RNA to so the virus achieves intended behavior. In case of CG007, the DNA of the virus was modified so the virus enters into every cell but it only replicate itself in the cell that has an Rb deficiency or defect which is often found in bladder cancer cell. This will ensure only bladder cancer cells will be be affected by CG0070 but not normal cells. In addition, CG0070 encodes the cDNA for human granulocyte macrophage-colony stimulating factor (GM-CSF), a cytokine known to be a potent inducer of specific, long-lasting antitumor immunity in animal model.
In short, CG0070 kills bladder cancer cells in two ways. One is by CG0070 (the virus) replicating in bladder cancer cell and bursting the cancer cell. The other is by the DNA of CG0070 enabling producing human granulocyte macrophage-colony stimulating factor (GM-CSF), which invokes dendritic cell, which then delivers antigen ( information) of bladder cancer to near by lymph nodes, which then produces the tumor specific T-cells which will kill bladder cancer cell. Because CG0070 invokes immune response and those immune cells kill bladder cancer cell, CG0070 is also called oncolytic immunotherapy. CG0070 is considered to give durability response because it invokes T-cells. The efficacy of CG0070 exceeded the efficacy of pembrolizumab (Keytruda) immunotherapy alone for BCG Unresponsive.
Also CG0070 and Pembrolizumab (Keytruda) combination has shown better efficacy than CG0070 alone CORE-1 phase 2 clinical trial.
The summary of efficacy of CG0070 and CG0070 + Pembrolizumab(Keytruda) immunotherapy
BOND-003 CG0070 alone Phase 3
CR at 6 months 44% and at 12 months 28% CG0070 alone
CORE-001 CG0070 + Pembrolizumab (Keytruda) combination Phase 2
Complete Repose Rate 82% at 6 months, 81% at 9 months and 68% 12 months.
Mechanism of Action of CG0070
https://lh7-us.googleusercontent.com/BaoICW3cXlRS1iWsO-xcq-WGKX10mRY-uPt1JqauBdYEFJfIcm78HPB5VXQxKkrUOIz1-2LtWdWi-Xw6WZT_iDTmzM-N0bgHPODQiT3Zl3hdwjizGrX83nFHPtKej3PbyYmb6Io81IZUTJ3Zn5u_gks
www.cancernetwork.com/view/cretostimogene-grenadenorepvec-yields-durable-responses-in-nmibc