A Clinical Trial of the Intradermal TLR2 Agonist CADI-05 for BCG Recurrent and Unresponsive Non-Muscle Invasive Bladder Cancer

O’Donnell, Michael A.; Singh, Shashank; Sood, Rajeev; amlani, jitendra; Krishnamoorthy, H; Shukla, Ketan; Mohanty, N.; Bhatia, Sushil; Chakraborty, Bhaswat S.; Desai, Nirav K.; Modi, Rajiv; Shukla, Chandreshwar; Vachhani, Kapil; Patel, Rashmi D; Kundu, Anup Kumar; Khamar, Bakulesh

doi:10.3233/blc-190211

Cited by 6 publications

(3 citation statements)

References 38 publications

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“…In a preliminary study of BCG recurrent/refractory NMIBC, DSC3 expression was associated with response to CADI-05 [54].…”

Section: Dsc3mentioning

confidence: 96%

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Immunotherapy of Bladder Cancer

Khamar¹

2020

Cancer Med J

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Bladder cancer used to be the only cancer treated by immunotherapy in form of intravesical BCG. Since approval of BCG for Non muscle invasive bladder cancer (NMIBC), there has been significant advancement in our knowledge about immune alteration in cancer and availability of immunotherapeutic agents. Tumor induced cell mediated immunosuppression is identified as a key factor for development and progression of cancer. Immune suppression in bladder cancer is predominantly through Macrophages. Myeloid derived suppressor cell, NK cells, Treg and expression of immune checkpoint receptor inhibitors also contribute to immune suppression. BCG induces innate immune response and its efficacy is limited to NMIBC. Novel immunotherapeutic agents evaluated in bladder cancer are administered locally or systemically to induce innate or adaptive immune response. Systemic administration of antibodies against PD-1/PD-L1 axis are now approved for treatment of locally advanced/metastatic bladder cancer as a first line as well as second line therapy. Pembrolizumab is also approved for BCG unresponsive NMIBC. Since response to immunotherapy are neither uniform nor universal, attempts are made to identify prognostic and predictive biomarkers. Identified biomarkers lack desired specificity and sensitivity. Several immune approaches using innate as well as adaptive mechanism are under evaluation to improve outcome of intravesical BCG or immune check point receptor inhibitors.

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“…In a preliminary study of BCG recurrent/refractory NMIBC, DSC3 expression was associated with response to CADI-05 [54].…”

Section: Dsc3mentioning

confidence: 96%

“…Unlike other immunomodulators. It also reduces immunosuppressive tumor microenvironment by decreasing intratumoral T reg, PD-1 while increasing activated intratumoral CD8+ T cells, NK cells and M1 macrophages [54,57]. It provides durable response in BCG recurrent/unresponsive DSC3 expressing NMIBC [53].…”

Section: Cadi-05mentioning

confidence: 99%

Immunotherapy of Bladder Cancer

Khamar¹

2020

Cancer Med J

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“…A phase II trial (NCT00694798) was performed by O’Donnell et al 10 in which 22 patients were recruited with intermediate to high-risk BU or BCG-recurrent (BR) NMIBC. The participants were followed up for 15 months.…”

Section: Cadi-05mentioning

confidence: 99%

A systematic review on the available treatment modalities for Bacillus Calmette–Guérin-unresponsive carcinoma in situ and tumors in patients who are ineligible for or decline radical cystectomy

et al. 2023

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Introduction: Globally, urothelial bladder carcinoma is a disease which carries a poor prognosis. There are various treatment modalities for urothelial bladder carcinoma with intravesical Bacillus Calmette–Guérin immunotherapy being the most efficacious intravesical therapy and the treatment of choice for patients with carcinoma in situ. A number of chemotherapeutic drugs are also available for the management of Ta/T1 tumors such as mitomycin C and epirubicin. However, relapse and progression is quite common. The optimal management of patients with Bacillus Calmette–Guérin-unresponsive disease remains to be a challenge. The purpose of this study was to conduct a systematic review on the treatment modalities available for the management of Bacillus Calmette–Guérin-unresponsive carcinoma in situ and urothelial bladder carcinoma in patients who are ineligible or decline radical cystectomy. Methods: Two authors independently searched three databases on the treatment modalities available for the management of Bacillus Calmette–Guérin-unresponsive carcinoma in situ and Bacillus Calmette–Guérin-unresponsive urothelial bladder carcinoma. Results: The systematic search resulted in 15 studies. We recommend the use of intravesical CG0070 adenovirus or hyperthermic intravesical chemotherapy mitomycin C in patients with carcinoma in situ only disease. In patients with carcinoma in situ ± Ta/T1 disease, we recommend the use of intravesical radiofrequency-induced chemohyperthermia or electromotive drug administration of mitomycin C. In patients who have Ta/T1 disease, we recommend the use of either hyperthermic intravesical chemotherapy epirubicin or electromotive drug administration mitomycin C followed by chemohyperthermia mitomycin C. If any of these second line therapies fail, an alternative regimen would be a combination of gemcitabine, cabazitaxel, and cisplatin. Conclusion: This recommendation is subject to the available resources and clinical expertise available in different hospitals. More studies using study designs such as randomized controlled trials comparing multiple drugs with larger sample sizes and regular follow-up intervals should be performed to accurately assess the different medications and aid in designing guidelines to guide the management of Bacillus Calmette–Guérin-unresponsive non-muscle invasive intravesical bladder cancer.

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