Cretostimogene Grenadenorepvec

In an advance that could improve bladder cancer treatment, a novel combination of cretostimogene grenadenorepvec and pembrolizumab has shown remarkable efficacy in patients with Bacillus Calmette-Gu rin (BCG)-unresponsive non-muscle invasive bladder cancer. Results from the phase 2 CORE-001 trial reveal a significant improvement in complete response rates and long-term disease control, offering new hope for patients with this challenging condition who face limited treatment options. In a groundbreaking advance that could revolutionize bladder cancer treatment, a novel combination of cretostimogene grenadenorepvec and pembrolizumab has shown remarkable efficacy in patients with Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer. Results from the phase 2 CORE-001 trial, published in Nature Medicine, reveal a significant improvement in complete response rates and long-term disease control, offering new hope for patients with this challenging condition who face limited treatment options. The trial included patients with BCG-unresponsive carcinoma in situ of the bladder, a condition that is notoriously difficult to treat and often leads to radical cystectomy. The combination therapy of intravesical cretostimogene grenadenorepvec (an intravesically delivered oncolytic immunotherapy) with systemic pembrolizumab (an immune checkpoint inhibitor) demonstrated a complete response rate of 57.1% at 12 months, surpassing previous benchmarks set by other therapies. The trial also demonstrated durable responses; findings show a complete response rate of 82.9% at three months, with a median duration of response not yet reached after a median follow-up of 26.5 months. "This study marks an important step forward in the treatment of BCG-unresponsive NMIBC," said Roger Li, M.D., principal investigator of the trial and urologic oncologist at Moffitt Cancer Center. "Our findings indicate that the combination of cretostimogene grenadenorepvec and pembrolizumab offers a unique, efficacious and durable bladder-preserving alternative strategy to radical cystectomy." The oncolytic immunotherapy directly enters the bladder cancer cells, destroys them, and then stimulates an anti-tumor response from the body's immune system. Pembrolizumab, a well-known PD-1 inhibitor, further enhances the immune system's ability to attack cancer cells. The observed clinical benefits stem from the synergistic effect of these two therapies. "These encouraging results highlight the potential for oncolytic immunotherapy to synergize with immune checkpoint inhibitors, offering a new avenue for patients who have exhausted other treatment options," Li said. "We are optimistic that additional clinical trials will confirm these benefits and support the integration of both monotherapy and combination therapies into the standard-of-care for BCG-unresponsive non-muscle invasive bladder cancer." The study noted that adverse events were manageable and consistent with those observed in previous monotherapy trials. The most common side effects related to cretostimogene were bladder-related symptoms, while pembrolizumab-related adverse events were typical of systemic immunotherapy.

– Final positive CORE-001 safety and efficacy findings were published simultaneously online by Nature Medicine and featured at ASCO 2024 – – 54% complete response (CR) rate in the intention-to-treat population at 24-month landmark and meets primary endpoint of the phase 2 study – IRVINE, Calif., June 06, 2024 (GLOBE NEWSWIRE) -- CG Oncology, Inc. (NASDAQ: CGON), a late-stage clinical biopharmaceutical company focused on developing and commercializing a potential backbone bladder-sparing therapeutic for patients with bladder cancer, today announced the publication in Nature Medicine of final results from the Company’s CORE-001 Phase 2 trial of cretostimogene plus pembrolizumab in BCG-unresponsive Non-Muscle Invasive Bladder Cancer (NIMBC). The article, titled “Oncolytic adenoviral therapy plus pembrolizumab in BCG-unresponsive non-muscle-invasive bladder cancer: the phase 2 CORE-001 trial” is now available online and will be published in a future print issue of Nature Medicine. The most recent data cut as of May 17, 2024, was also featured as a poster at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. “The CORE-001 trial results published in Nature Medicine clearly demonstrate the potential for cretostimogene to be used as a bladder-sparing backbone therapy for NMIBC,” said Vijay Kasturi, MD, Chief Medical Officer, CG Oncology. “We are honored that Nature Medicine and ASCO are publishing our compelling safety and efficacy phase 2 study results, which showed a class-leading complete response (CR) and duration of response (DoR) compared to existing FDA-approved therapies and other investigational candidates.” “As a principal investigator on both the BOND-003 Phase 3 monotherapy clinical trial as well as the CORE-001 Phase 2 combination trial it is especially gratifying to see the studies culminating in such strong results,” said Roger Li, M.D., urologic oncologist at Moffitt Cancer Center. “These data highlight the promise of cretostimogene’s novel mechanism of action, providing both direct tumor cell kill while activating an anti-tumor immune response. I believe cretostimogene as an oncolytic immunotherapy has the potential to act as the backbone to multiple treatment strategies in the new bladder sparing paradigm in bladder cancer management.” As previously shared in the Company’s May 24th press release, the CORE-001 Final Results are as follows: As of the data cutoff on February 5, 2024, the CR rate in the intention-to-treat (ITT) population at 12-months and any time, was 57% (20/35) [95% confidence interval (CI), 40-73%] and 83% (29/35) (95% CI, 70-95%), respectively. As of May 17, 2024, the CR rate in the ITT population at 24 months was 54% (19/35) (95% CI, 37-71%). Of the patients in a CR at 12 months, 95% of patients (19/20) maintained a CR for another 12 months. Median DoR has not been reached but exceeds 21 months. Additionally, the Kaplan-Meier estimates for CR rate at 12- and 24 months were 77.3% (95% CI, 58.1-88.5%) and 69.6% (95% CI, 49.4-83.0%), respectively. Progression-free survival (PFS) at 24 months is 100% with no patients progressing to muscle invasive cancer or metastatic disease; Cystectomy-free survival (CFS) at 24 months was 80%; for patients in CR, CFS at 24 months was 100%. Treatment-related adverse events (TRAEs) were consistent with the individual agents and demonstrate no synergistic toxicity. Results to be presented are an update from previously reported data in the abstract. The Phase 2 CORE-001 trial was conducted in collaboration with Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. The combination of cretostimogene and pembrolizumab received FDA Breakthrough Therapy Designation in May 2023. Cretostimogene monotherapy received FDA Fast Track and Breakthrough Therapy Designations in BCG-Unresponsive, HR-NMIBC with CIS in December 2023. CG Oncology recently presented data from the Phase 3 BOND-003 trial at the 2024 American Urological Association Annual Meeting which showed sustained durable responses over 12 months and a 75.2% complete response rate at any time. Topline data from BOND-003 is expected by the end of 2024, and the Company is on track for a regulatory approval submission. To learn more about the results from BOND-003 you may read the Company’s press release issued on May 3, 2024. About Cretostimogene Grenadenorepvec Cretostimogene is an investigational, intravesically delivered oncolytic immunotherapy being evaluated in BOND-003, a Phase 3 clinical trial for the treatment of patients with high-risk Non-Muscle Invasive Bladder Cancer (NMIBC) who are unresponsive to Bacillus Calmette Guerin (BCG) therapy. Cretostimogene is also being evaluated in a Phase 3 monotherapy clinical trial (PIVOT-006) in intermediate-risk NMIBC patients. In addition, cretostimogene is being evaluated in an investigator-sponsored clinical trial in combination with nivolumab for the treatment of muscle invasive bladder cancer. Cretostimogene is an investigational, intravesically delivered oncolytic immunotherapy candidate, and its safety and efficacy have not been established by the FDA or any other health authority. About the CORE-001 Study CORE-001 was a Phase 2 single-arm, open-label clinical trial of cretostimogene administered in 35 patients with high-risk, BCG-unresponsive NMIBC that have carcinoma in situ-containing tumors, in combination with pembrolizumab, following disease resection. CORE-001 was conducted pursuant to a clinical collaboration and supply agreement with Merck (known as MSD outside the United States and Canada). More information about the study, CORE-001 (NCT04387461), along with other studies sponsored by CG Oncology, can be found at or . About CG Oncology CG Oncology is a late-stage clinical biopharmaceutical company focused on developing and commercializing a potential backbone bladder-sparing therapeutic for patients afflicted with bladder cancer. CG Oncology sees a world where urologic cancer patients may benefit from our innovative immunotherapies to live with dignity and have an enhanced quality of life. To learn more, please visit: . Forward Looking Statements CG Oncology cautions you that statements contained in this press release regarding matters that are not historical facts are forward-looking statements. The forward-looking statements are based on our current beliefs and expectations and include, but are not limited to, the potential therapeutic benefits of cretostimogene in combination with pembrolizumab for high-risk NMIBC patients and the importance of the data as they relate to addressing bladder cancer and supporting further investigation in combination with checkpoint inhibitors; the anticipated timing of BOND-003 final data; and the Company’s expectations on a regulatory approval submission. Actual results may differ from those set forth in this press release due to the risks and uncertainties inherent in our business, including, without limitation: additional patient data related to cretostimogene in combination with pembrolizumab that continues to become available may be inconsistent with the data produced as of the data cutoff, and further analysis of existing data and analysis of new data may lead to conclusions different from those established as of the date hereof; results from earlier clinical trials and preclinical studies not necessarily being predictive of future results; unexpected adverse side effects or inadequate efficacy of cretostimogene that may limit its development, regulatory approval, and/or commercialization; potential delays in the commencement, enrollment and completion of clinical trials; and other risks described in our filings with the Securities and Exchange Commission (SEC), including under the heading “Risk Factors” in our annual report on Form 10-K and other filings that we make with the SEC from time to time (which are available at ). You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and we undertake no obligation to update such statements to reflect events that occur or circumstances that exist after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Contacts: Media Sarah Connors Vice President, Communications and Patient Advocacy, CG Oncology (508) 654-2277 sarah.connors@cgoncology.com Investor Relations Laurence Watts New Street IR (619) 916-7620 IR@cgoncology.com