CG Oncology Announces Nature Medicine Publication of Final Results from CORE-001 Study of Cretostimogene Grenadenorepvec in Combination with Pembrolizumab in BCG-Unresponsive NMIBC

Rhea-AI Summary

CG Oncology (NASDAQ: CGON) has published final results from its Phase 2 CORE-001 trial of cretostimogene and pembrolizumab in BCG-unresponsive Non-Muscle Invasive Bladder Cancer (NMIBC) in Nature Medicine and presented them at ASCO 2024.

The trial met its primary endpoint with a 54% complete response (CR) rate at 24 months in the intention-to-treat (ITT) population. The 12-month CR was 57%, with 95% of these patients maintaining CR for an additional 12 months.

Progression-free survival (PFS) at 24 months was 100%, with no patients advancing to muscle invasive or metastatic disease. Cystectomy-free survival (CFS) at 24 months was 80%, and 100% for patients in CR. Treatment-related adverse events were consistent with those of the individual agents.

The combination received FDA Breakthrough Therapy Designation in May 2023, and cretostimogene monotherapy also received Fast Track and Breakthrough Therapy Designations in December 2023. Topline data from the Phase 3 BOND-003 trial is expected by the end of 2024.

Positive

• 54% complete response rate at 24 months in the ITT population.
• 95% of patients who had a 12-month CR maintained it for an additional 12 months.
• 100% progression-free survival at 24 months.
• 80% cystectomy-free survival at 24 months.
• No patients progressed to muscle invasive or metastatic disease.
• The combination received FDA Breakthrough Therapy Designation in May 2023.
• Cretostimogene monotherapy received FDA Fast Track and Breakthrough Therapy Designations in December 2023.
• The trial results were published in Nature Medicine and featured at ASCO 2024.

Negative

• Cystectomy-free survival at 24 months for the entire ITT population was 80%, indicating 20% underwent cystectomy.
• Long-term durability beyond 24 months is not established.
• Potential for treatment-related adverse events, though consistent with individual agents, was not elaborated in detail.

Medical Research Analyst

The final results of the CORE-001 Phase 2 trial indicate promising efficacy and safety for the combination of cretostimogene and pembrolizumab in treating BCG-unresponsive Non-Muscle Invasive Bladder Cancer (NMIBC). A key highlight is the 54% complete response (CR) rate at the 24-month landmark, which suggests that a significant proportion of patients achieved tumor-free status. Notably, the 100% progression-free survival (PFS) at 24 months and 80% cystectomy-free survival (CFS) are substantial, indicating that the treatment helps in delaying or even avoiding more invasive therapies. These results are quite impressive given the challenging nature of BCG-unresponsive NMIBC.

However, while the results are promising, it is important to consider that this is still a Phase 2 study. The outcomes need to be confirmed in larger Phase 3 trials to fully ascertain the benefit-risk profile. The study's median duration of response (DoR) exceeding 21 months also points towards durable effects, but the exact median isn't reached yet, which warrants further observation.

For retail investors, the news signifies a potential breakthrough, but it's important to keep an eye on the upcoming Phase 3 results for a more comprehensive view of the therapy's efficacy and safety. The promising data supports a positive outlook, but cautious optimism is advisable until further validations.

Financial Analyst

The publication of the CORE-001 study results in a prestigious journal like Nature Medicine and their presentation at ASCO 2024 significantly bolster CG Oncology's credentials. This kind of high-profile validation can drive investor confidence and potentially lead to a stock price increase given the positive market sentiment around breakthrough oncology treatments. The fact that the complete response (CR) rates and progression-free survival (PFS) metrics surpass existing standards is noteworthy and can position CGON as a leading player in the NMIBC treatment market.

Furthermore, the FDA's Breakthrough Therapy Designation and Fast Track status for cretostimogene highlight the regulatory support and expedited review pipelines, potentially accelerating market entry. However, investors should be aware that despite the optimistic results, the transition from promising Phase 2 results to market-ready treatments can face hurdles including stringent Phase 3 results and competitive dynamics.

In the short term, positive market reactions can be expected, especially with any further positive announcements related to the Phase 3 BOND-003 trials. In the long term, sustained performance and market penetration will depend on successful regulatory approvals and the ability to compete with or complement existing treatment options effectively.

– 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 www.clinicaltrials.gov or www.cgoncology.com.

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: www.cgoncology.com.

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 http://www.sec.gov). 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

FAQ

What were the final results of CG Oncology's CORE-001 trial?

The final results of the CORE-001 trial showed a 54% complete response rate at 24 months in the intention-to-treat population.

What is the purpose of the CORE-001 trial?

The CORE-001 trial aims to evaluate the combination of cretostimogene and pembrolizumab in BCG-unresponsive Non-Muscle Invasive Bladder Cancer (NMIBC).

When were the final CORE-001 trial results published?

The final results were published in Nature Medicine and presented at the ASCO 2024 annual meeting.

What is the significance of the FDA Breakthrough Therapy Designation for CGON?

The combination of cretostimogene and pembrolizumab received FDA Breakthrough Therapy Designation in May 2023, indicating its potential as a significant treatment for NMIBC.

What is the complete response rate at 12 months in the CORE-001 trial?

The complete response rate at 12 months was 57%, with 95% of these patients maintaining a complete response for another 12 months.

What survival rates were observed in the CORE-001 trial?

At 24 months, progression-free survival was 100%, and cystectomy-free survival was 80% for the entire ITT population and 100% for patients in complete response.

When is the topline data from the BOND-003 trial expected?

Topline data from the BOND-003 trial is expected by the end of 2024.