Mining the opportunities
within the current therapeutic landscape
Although treatment options have expanded, there remains a need for durable and tolerable treatment options in BCG-unresponsive NMIBC
Currently, treatments that provide an alternative to radical cystectomy fall into 4 main categories1
Intravesical
chemotherapy
Systemic
immunotherapy
Gene Therapy
IL-15 receptor agonist
Achieving reliable and sustainable efficacy with a bladder- sparing therapy may be possible with options that:
- Selectively target bladder cancer cells2,3
- Do not require combination with BCG, which brings inherent access problems associated with the BCG shortage, thereby limiting its practicality in the real world4,5
- Improve efficacy and durability of response, given that rates of recurrence and progression remain high, often resulting in radical cystectomy5-9
- Leverage familiar intravesical administration procedures and schedules that easily integrate into current urology practice10,11
- Have a safety and tolerability profile that helps mitigate the barriers to improved compliance and adherence12,13
There remains a clinical and practical need for treatment options that selectively target bladder cancer cells and demonstrate durable, bladder-sparing outcomes that are easy to integrate into urology practice
Oncolytic immunotherapy represents a highly
promising approach for BCG-unresponsive NMIBC
Oncolytic immunotherapy uses genetically modified viruses that replicate within tumor cells, causing cell lysis and release of viral- and tumor-specific antigens, which in turn trigger the body’s immune system to recognize and attack remaining cancer cells.14
Specific modifications to oncolytic immunotherapy can enable desirable therapeutic characteristics such as tumor selectivity (and hence, sparing of normal cells) and amplification of the body’s anti-tumor immune response.14
Each administration of oncolytic immunotherapy further disrupts the tumor microenvironment, making cancer cells more vulnerable to immune attack. This means that even if not all cancer cells were eliminated during the first treatment, they might be more susceptible upon repeat administration.15
Oncolytic immunotherapy stimulates both the innate and adaptive immune responses to create a robust, multifaceted attack against cancer. The innate immune response provides an immediate reaction to the viral and tumor-specific antigens, while the adaptive response generates a targeted, long-term defense, leading to enhanced and durable anti-tumor activity.15
High-risk bladder cancer patients: future treatment options for BCG-unresponsive/naïve NMIBC
Trinity J. Bivalacqua, MD, PhD, Professor of Urology and Oncology at the Perelman Center for Advanced Medicine, University of Pennsylvania discusses future treatment options for patients with high-risk non-muscle invasive bladder cancer that are BCG naïve or BCG unresponsive.
Transcript: The BCG shortage has had profound effects on patient’s ability to get into a urologist and receive adequate and effective intravesical therapy. We know that BCG is the most effective way to treat high risk non-muscle invasive bladder cancer. If BCG is not available, then obviously we have other options which include intravesical chemotherapy. With the BCG shortages that are now permanent here in the United States, as well as around the world, a lot of patients aren’t able to get the best treatment for their high-risk non-muscle vasal bladder cancer. So, this has translated into a lot of patients that are seeing more risk recurrence and potentially needing a major surgery, things like radical cystectomy. I think in the future, our goal as a community is to help develop alternative options for patients that are not able to receive BCG due to BCG shortages or are intolerant of BCG, that can’t tolerate it.
Oncolytic immunotherapy may mean a future with more bladder-sparing options for patients with high-risk BCG-unresponsive NMIBC
Explore highly promising areas of ongoing clinical research
To learn more about the CG Oncology clinical program, contact Medical Affairs at medicalaffairs@cgoncology.com
BCG=bacillus Calmette-Guérin; NMIBC=non-muscle invasive bladder cancer.
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REFERENCES:
1. Flaig TW, Spiess PE, Abern M, et al. NCCN Guidelines® Insights: Bladder Cancer, Version 3.2024. J Natl Compr Canc Netw. 2024;22(4):216-225.
2. Rahman MM, McFadden G. Oncolytic viruses: newest frontier for cancer immunotherapy. Cancers (Basel). 2021;13(21):5452.
3. Ramesh N, Ge Y, Ennist DL, et al. CG0070, a conditionally replicating granulocyte macrophage colony stimulating factor armed oncolytic adenovirus for the treatment of bladder cancer. Clin Cancer Res. 2006;12(1):305-313.
4. Ostrowski DA, Chelluri RR, Herzig M, et al. Diminished short term efficacy of reduced dose induction BCG in the treatment of non muscle invasive bladder cancer. Cancers. 2023;24;15(14):3746.
5. ANKTIVA® (nogapendekin alfa inbakicept pmln) Prescribing Information. ImmunityBio, Inc.; 2024.
6. ADSTILADRIN® (nadofaragene firadenovec vncg) Prescribing Information. Ferring Pharmaceuticals; 2023.
7. Valstar (valrubicin) Prescribing Information. Endo Pharmaceuticals Inc.; 2016.
8. Keytruda® (pembrolizumab) Prescribing Information. Merck & Co., Inc.; 2024.
9. Hannouneh ZA, Hijazi A, Alsaleem AA, et al. Novel immunotherapeutic options for BCG-unresponsive high-risk non-muscle-invasive bladder cancer. Cancer Med. 2023;(24):21944-21968.
11. AUA/SUNA. Intravesical administration of therapeutic medication for the treatment of bladder cancer. Revised June 2020. Accessed April 14, 2025. https://www.auanet.org/about-us/policy-and-position-statements/intravesical-administration-of-therapeutic-medication.
12. Mori K, Miura N, Babjuk M, et al. Low compliance to guidelines in nonmuscle invasive bladder carcinoma: a systemic review. Urol Oncol. 2020;38(10):774-782.
13. Grabe-Hayne K, Henne C, Mariappan P, et al. Intermediate and high-risk non-muscle-invasive bladder cancer: an overview of epidemiology, burden, and unmet needs. Front Oncol. 2023;13:1 17.
14. Yan Z, Zhang Z, Chen Y, Xu J, Wang J, Wang Z. Enhancing cancer therapy: the integration of oncolytic virus therapy with diverse treatments. Cancer Cell Int. 2024;24(1):242.
15. Zhang Y, Li Y, Chen K, Qian L, Wang P. Oncolytic virotherapy reverses the immunosuppressive tumor microenvironment and its potential in combination with immunotherapy. Cancer Cell Int. 2021;21(1):262.