FDA Approval of TAR-200 Represents Potential Bladder-Sparing Option in BCG-Unresponsive NMIBC

Along with serving as a novel treatment modality for patients with BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC), the gemcitabine intravesical system (formerly TAR-200; Inlexzo) could serve as a technique to help patients avoid radical cystectomy and the quality-of-life changes associated with the surgery, according to Joseph Jacob, MD, MCR.

“This is a drug that's going to save a lot of bladders,” Jacob said in an interview with OncLive®.

On September 9, 2025, the FDA approved TAR-200 for the treatment of adult patients with BCG-unresponsive NMIBC with carcinoma in situ (CIS), with or without papillary tumors, based on data from cohort 2 of the phase 2b SunRISe-1 trial (NCT04640623).1 Findings supporting the approval showed that patients treatment with TAR-200 (n = 83) experienced a complete response (CR) rate of 82% (95% CI, 72%-90%).2 Response duration ranged from 0+ months to 44+ months, and 51% of patients achieved a duration of response (DOR) of at least 12 months.

In the interview, Jacob expanded on the significance of the FDA approval of TAR-200, highlighted the key data from cohort 2 of SunRISe-1 that supported the regulatory decision, and detailed how the intravesical delivery of drugs could help shift the management of bladder malignancies.

Jacob is an associate professor of urology at Upstate Medical University in Syracuse, New York.

OncLive: What is the significance of the FDA approval of TAR-200 for BCG-unresponsive NMIBC with CIS, with or without papillary tumors? How does this address an unmet need for this patient population?

Jacob: This is significant on many levels. On the first basic level, this is a population of patients who really have had no options in the past. They had some medicines that didn’t work very well, and then the alternative [treatment] would be radical cystectomy, which is a pretty significant surgery with its own quality-of-life changes.

In the last few years, we've had some new drugs available. TAR-200 is a new drug that's available and works really well, and it is going to be really effective therapy for patients going forward.

The second part, just from a scientific standpoint, is that we've never done this before. We've never treated any kind of bladder pathology—let alone bladder cancer—with an intravesical device. Therefore, this is a paradigm shift, almost for the treatment of bladder pathologies in general. The fact that we were able to find a technology that is inserted in the bladder and can consistently deliver a drug over a period of a week is paradigm-shifting.

How was the SunRISe-1 trial designed to evaluate TAR-200 in this patient population?

[The SunRISe-1 trial design was] actually complicated. There were [4] cohorts, and the cohort that I'm going to focus on is cohort 2. [SunRISe-1] started off as a randomized trial. The first cohort was TAR-200 plus cetrelimab, which is an [immune] checkpoint inhibitor. The second cohort, which we'll focus on and [supported the] approval, was TAR-200 monotherapy, and the third cohort was cetrelimab monotherapy. Later, cohort 4 was added, which was TAR-200 monotherapy for patients with papillary-only disease.

As time went on and the data were developing, cohorts 1 and 3 were closed, and then cohort 2 remained open because of the results. Cohort 4 was [later] added as an exploratory cohort.

The trial consisted of patients with BCG-unresponsive, high-risk NMIBC with CIS, with or without papillary disease. In cohort 2, patients received TAR-200 monotherapy every 3 weeks for the first 24 weeks, then every 3 months thereafter through week 96. They were assessed by central cytology and pathology [with] mandated biopsies at weeks 24 and 48, as well as a quarterly cystoscopy and cytology. This highlights that [the trial] was stringent in terms of assessment criteria. The primary end point that was used for the FDA approval was the overall CR rate at any time point. Secondary end points were DOR, overall survival, safety, and tolerability.

What were the key efficacy findings from cohort 2 that supported the FDA approval of TAR-200?

This [CR rate] is the highest number we've seen so far, which that's one of the reasons why we're so excited about [TAR-200]. This was 82% based on central review…and most of these responses were achieved pretty quickly within the first disease assessment. One thing to highlight that's important and differentiates TAR-200 from some of the other trials:if patients [experienced disease recurrence] on trial, they were not allowed to receive more therapy. In some of the other trials, investigators were allowed to retreat or reinduce patients. [In SunRISe-1], these were patients [who came off the study right way] if they recurred or had persistent disease. Therefore, you can tell just with the induction phase of treatment that [TAR-200] is a very effective drug. [Responses] were also durable. Fifty-one percent of them responded for over 1 year or more.

What should clinicians know regarding the safety profile of TAR-200?

This is a safe drug. Most adverse effects [AEs] were urinary in nature. Not surprisingly, these patients experienced frequency in urination. However, there were very few treatment discontinuations at less than 5% due to AEs, and there were no deaths.

How does TAR-200 now fit into the NMIBC treatment paradigm?

Based on the approval, this is going to be a second-line drug after patients have [not responded to] BCG. That said, there are ongoing trials to see where [else TAR-200] will fit in, and likely this will fit in within other disease spaces. However, right now, we're going to be using it for the patients with BCG-unresponsive [NMIBC].

From a patient standpoint, you have patients who are used to getting treatment once a week, every 6 weeks with some of the other drugs. [TAR-200] is a more convenient therapy to give. Patients are receiving this every 3 weeks, and especially for my patients who are traveling from a distance, this can be a lot more convenient for them.

References

1. FDA approves gemcitabine intravesical system for non-muscle invasive bladder cancer. FDA. September 9, 2025. Accessed October 14, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-gemcitabine-intravesical-system-non-muscle-invasive-bladder-cancer
2. Inlexzo. Prescribing information. Johnson & Johnson; 2025. Accessed October 14, 2025. https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/INLEXZO-pi.pdf