Bladder cancer presents a complex challenge that demands innovative approaches to treatment. In recent years, significant progress has been made in the development of intravesical delivery systems for targeted therapy in bladder cancer patients. This article aims to provide a comprehensive overview of the latest advancements in intravesical delivery systems, with a particular focus on the TAR200 and TAR21210 systems. The application of intravesical delivery systems holds profound clinical significance in the treatment of bladder cancer. These systems provide a continuous and controlled exposure of the tumor to therapeutic agents, significantly enhancing the likelihood of successful treatment outcomes. Moreover, intravesical delivery systems offer a valuable alternative to radical cystectomy, a surgical procedure that certain patients may decline or be medically unfit for. The ultimate goal is to preserve the bladder while achieving a cure and preventing disease progression.
Q1: Hi Professor Necchi , thank you so much for attending this interview. Could you introduce what kind of new delivery system TAR-210 is?
A: Yeah, thank you. TAR200 is a new intravestical delivery system that allows a stable release of gem -cyteabene through a silicon tube that is, that osmotically released the gem -cyteabene into the bladder.
It’s a small silicon tube that is put into the bladder via a cystoscopy, so a very, very easy endoscopy procedure, and is removed every three weeks, recharged and then replaced into the bladder. So this way we can allow a continuous exposure of the tumor to the drug, and this is the key of success, so the total exposure time for the tumor to the drug seems to be, to make the key and the differences compared to other ways of installation of chemotherapy or other drugs in this disease.
Q2: Could you please share the SunRISe-1 study you presnented at this congress? What is the clinical significance of this study?
A: Well, the SunRISe-1 is a part of a platform study testing TAR -200 as monotherapy or in combination with the immune checkpoint inhibitors or Cetrelimab, NTP -1 agent in various disease stages.
The SunRISe-1 in particular is a randomized face -to -be open -label study in which patients are randomized to receive a TAR -200 in combination with the Cetrelimab in CORT -1, TAR -200 in monotherapy in CORT -2, or Cetrelimab in monotherapy in CORT -3.
There is an additional CORT of patients that is included in this currently enrolling patients that is CORT -4. It is included in patients with the papillary, high -risk, non -muscle invasive disease who develop a visage on responsive disease.
Importantly, CORT -1, 2, and 3 are included in patients with the Casino -Minside disease. to component with or without a papillary disease who have already experienced a BCG failure and who has already received a sufficient number of BCG intravascular in order to define them as having a BCG unresponsive disease.
The standard of care for experimental radical cystectomy and these patients are refusing or unfit for radical cystectomy. These patients, the data that we have reported here are relative to the monotherapy quarter, so the quarter two in which it are 200 is those every three weeks for the first 24 weeks and then every 12 weeks until week 96 and the primary point is the complete response rate and the complete response is evaluated centrally with the centralized assessment of urine cytology biopsies at two different time points of week 24 and 48.
Q3: For LBA 104 presented at the same session, TAR-210 was used for NMIBC with FGFR alteration. Does your research also include analysis of biomarkers such as PD-L1?
A: Yeah. So the TAR-210 is a similar way, pursues a similar way of delivery in therapy, and basically in this case, we don’t have chemotherapy, but we have a first targeted therapy that is delivered locally.
TAR-210 was a study which investigated the delivery of treatment in patients with intermediate risk, non -muscle invasive blood cancer. The primary point was their current free survival rate, or disease free survival rate, and the initial data, but very short term, follow up quite promising, more than 80% relapse free survival in this patient population, so quite promising.
These patients were selected according to FGF receptor molecular alteration. So basically, we don’t have at least at the moment information on the PDL1 expression of these patients. Of course, it’s something that is being, is it the pipeline of the analysis of the study, but we still do not have, and presumably, the PDL1 expression should be low in this patient population.
Q4: At this congress, you also conducted the speech on the progression of NMIBC to MIBC. What implications does this progress have for our clinical treatment?
A: Yeah, the point of disease progression in this patient population is still live, and this is the reason why there is a huge investment, and there is a large number of clinical trials that are investing in the searching for new drugs systemically or intravestically in this patient population, population across the border of high risk, non -muscle invasive disease, and early muscle invasive disease.
So this is a potentially deadly disease, so there is a lot of research ongoing, testing newer combinations, in particular testing the combination that provided the… a new standard of care in front line metastatic setting like ADC and immunotherapy combination.
But there are also combination of therapies like TART -1, so intravascular therapy and systemic therapy or combination of immunotherapies. So the point here is to try to cure the patients and to avoid the progression of the disease without going towards radical cystectomy.
So sparing the bladder to these patients and achieving the goal of a cure. Our last question is about during this other conference there are many like new reasons. Why do we scissors and yes, Oberlul mouths, we Well, of course, as oncologists, we are all impressed by the data of EV -302 study.
So, in Fortunum Averotin and Pembrolyzumabene, in front line, metastatic setting that changed the way and potentially will change the way we conceive the treatment of patients with a metastatic blood cancer.
There has been also that interesting with the combination of immune therapy and evolumab and cisplatin based chemotherapy in front line. Also achieving the primary point with the magnitude of improvement in survival that was lower than that achieved with the e -V -Pembro.
But there is still an opportunity I guess for this combination at least for selected patients. Mainly we will work for the next meeting on the patient selection and on biomarkers that may allow us to identify the patients who are best suited for certain therapeutic strategies.
So patient selection and therapy selection is the key in the near future. Thank you.
