FDA Grants Fast Track, Breakthrough Designations to CG Oncology Inc’s Cretostimogene Grenadenorepvec

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Cretostimogene grenadenorepvec (CG0070) is currently being evaluated for the treatment of patients with high-risk Bacillus Calmette-Guérin–unresponsive non–muscle invasive bladder cancer with carcinoma in situ with or without Ta or T1 tumors.

The FDA granted Fast Track and Breakthrough Therapy designations to CG Oncology Inc’s cretostimogene grenadenorepvec (CG0070) for the treatment of patients with high-risk Bacillus Calmette-Guérin (BCG)–unresponsive non–muscle invasive bladder cancer (NMIBC) with carcinoma in situ with or without Ta or T1 tumors.1 The novel, intravesically delivered oncolytic immunotherapy is currently being evaluated in the Phase III BOND-003 and the Phase II CORE-001 clinical trial in combination with pembrolizumab (Keytruda) in the same indication. An investigator-sponsored clinical trial is evaluating cretostimogene grenadenorepvec in combination with nivolumab (Opdivo) for the treatment of muscle invasive bladder cancer.

The regulatory action was based on data from an ongoing clinical trial program, including the Phase III BOND-003 trial (NCT04452591), which demonstrated that treatment with the intravesically delivered oncolytic immunotherapy provided clinical benefit in complete responses (CRs) with acceptable tolerability.

“Receiving both FDA Fast Track and Breakthrough Therapy Designation is an important milestone in the development of cretostimogene grenadenorepvec and for patients with bladder cancer who urgently need more therapeutic options,” Ambaw Bellete, president and chief operating officer, CG Oncology, said in a press release.1 “We are encouraged by this momentum following our recent announcement of first results from our Phase III BOND-003 study for patients with high-risk BCG-unresponsive NMIBC. CG Oncology looks forward to working with the FDA to advance cretostimogene grenadenorepvec as a potential backbone therapy in bladder cancer. We would like to thank the patients, caregivers, investigators and their staff who have participated in the clinical trials.”

BOND-003 is an open-label, single-arm study that enrolled 116 patients with high-risk NMIBC with carcinoma in situ with or without Ta/T1 disease who were BCG unresponsive, and patients persistent or recurrent disease within one year of BCG therapy completion.2 Enrollment criteria included an ECOG performance status of 0 to 2, acceptable organ function, and patients could not be candidates for, or must have refused, radical cystectomy. Exclusion criteria included upper tract or prostatic urethra malignancy, previous administration of adenovirus-based cancer therapy, and muscle-invasive or locally advanced metastatic bladder cancer.

Patients received cretostimogene grenadenorepvec intravesically followed by a sequence of bladder washes with 5% DDM and normal saline. Cretostimogene grenadenorepvec was administered weekly from weeks one to six, while patients with persistent high-grade disease at week 13 were administered an additional cycle of six weekly treatments. Patients with no disease at week 13 were administered three weekly treatments. At week 25, patients were administered three weekly treatments every 12 weeks through week 49 and every 24 weeks thereafter.3

The trial’s primary endpoint was CR at any time, with key secondary endpoints of duration of response, progression-free survival, time to progression, and safety. At a data cutoff date of October 5, 2023, cretostimogene grenadenorepvec was found to produce an anytime CR rate of 75.7% among 66 patients who were evaluable for efficacy, with CR rates at three and six months of 68.2% and 63.6%, respectively.2

“The Bladder Cancer Advocacy Network (BCAN) is grateful for the expedited review of this potential treatment option for bladder cancer patients with high-risk BCG-unresponsive NMIBC. What patients and their loved ones desperately need are more and better ways to treat their disease,” said BCAN Chief Executive Officer Andrea Maddox-Smith said in a press release.1 “We appreciate the urgency demonstrated by the FDA in recognizing the potential of this therapy.”


  1. CG Oncology receives both FDA fast track and breakthrough therapy designation for cretostimogene grenadenorepvec in high-risk BCG-unresponsive non-muscle invasive bladder cancer. News release. CG Oncology, Inc. December 5, 2023. Accessed January 4, 2024. https://cgoncology.com/cg-oncology-receives-both-fda-fast-track-and-breakthrough-therapy-designation-for-cretostimogene-grenadenorepvec-in-high-risk-bcg-unresponsive-non-muscle-invasive-bladder-cancer/
  2. Cretostimogene grenadenorepvec monotherapy first results show 75.7% complete response rate at any time in patients with high-risk BCG-unresponsive non-muscle-invasive bladder cancer. News release. CG Oncology, Inc. November 30, 2023. Accessed January 4, 2024. https://cgoncology.com/cretostimogene-grenadenorepvec-monotherapy-first-results-show-75-7-complete-response-rate-at-any-time-in-patients-with-highrisk-bcg-unresponsive-non-muscle-invasive-bladder-cancer/
  3. Study of CG0070 given in patients with non-muscle invasive bladder cancer, unresponsive to Bacillus-Calmette-Guerin (BOND-003). ClinicalTrials.gov. Updated May 12, 2023. Accessed January 4, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT04452591

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