CG Oncology Reports Positive Phase 3 Trial for Bladder Cancer Treatment

CG Oncology shares rose after reporting durability data for bladder cancer drug cretostimogene in a Phase 3 trial. The biopharmaceutical company's lead candidate, BOND-003, is a targeted oncolytic immunotherapy agent for non-muscle invasive bladder cancer. Its other product candidate, CORE-001, is in Phase II for BCG-unresponsive NMIBC, and PIVOT-006 is a Phase III trial assessing adjuvant cretostimogene for intermediate-risk NMIBC.

CG Oncology, a biopharmaceutical company specializing in targeted oncolytic immunotherapy agents, reported encouraging durability data for its lead candidate, cretostimogene, in a Phase 3 trial for non-muscle invasive bladder cancer (NMIBC) [1]. This trial, known as PIVOT-006, is designed to assess the efficacy and safety of intravesical cretostimogene after transurethral resection of bladder tumor (TURBT) versus TURBT alone.

NMIBC accounts for approximately 70-80% of all bladder cancer cases, and current guidelines recommend adjuvant intravesical therapy or surveillance for intermediate-risk patients [1]. However, these recommendations lack level-1 evidence, and 30-60% of patients still experience recurrences [1]. Cretostimogene, an oncolytic adenovirus, is designed to selectively replicate in and kill cancer cells, making it a promising candidate for improved therapies in the adjuvant setting.

The vector used in cretostimogene is transcriptionally regulated by the E2F promoter, which is up-regulated in retinoblastoma (Rb) pathway-defective tumor cells, a common characteristic in most intermediate-risk NMIBC bladder tumors [1]. Additionally, the virus is engineered to selectively express granulocyte-macrophage colony-stimulating factor (GM-CSF), inducing a robust systemic anti-tumor immune response.

PIVOT-006 is a randomized, open-label, multi-center study that enrolled 450 participants with IR-NMIBC, defined as either a low-grade (LG) stage Ta tumor that recurs within 12 months of prior LG or high-grade (HG) bladder cancer, a solitary LGTa tumor 3cm in size, multifocal LGTa tumors, primary HGTa lesion 3cm in size, or a LG1 tumor [1]. Participants were stratified by receipt of perioperative chemotherapy and tumor grade and randomly assigned to receive intravesical cretostimogene (Cohort 1) adjuvant to TURBT or TURBT alone (Cohort 2).

In Cohort 1, intravesical cretostimogene was instilled in combination with n-dodecyl-B-D-maltoside (DDM) for 6 weekly doses during the induction phase, followed by 3 weekly maintenance cycles at months 3 and 6, and culminating in single intravesical doses at months 9 and 12 [1]. Primary disease assessments include serial cystoscopy, urine cytology, axial imaging, and centralized review of pathologic samples, with the primary outcome measure being recurrence-free survival.

The data reported thus far show that cretostimogene has the potential to significantly improve outcomes for patients with intermediate-risk NMIBC. As the trial progresses, we will continue to monitor the results and provide updates on this promising therapy.

[1] https://ascopubs.org/doi/10.1200/JCO.2024.42.4_suppl.TPS715