TAR-200 Monotherapy Displays Early Efficacy in BCG-Unresponsive NMIBC

Sia Daneshmand, MD, discusses the rationale for investigating TAR-200 for the treatment of patients with Bacillus Calmette-Guérin-unresponsive, high-risk non–muscle-invasive bladder cancer, expands on the preliminary efficacy and safety data from the SunRISe-1 trial, and more.

Sia Daneshmand, MD

Sia Daneshmand, MD

After treatment with TAR-200 (GemRIS) monotherapy generated a high rate of complete responses (CRs) in patients with Bacillus Calmette-Guérin (BCG)–unresponsive, high-risk non–muscle-invasive bladder cancer (NMIBC) in the phase 2b SunRISe-1 trial (NCT04640623), the next steps will be to evaluate the durability of responses and whether the novel intravesical drug delivery system could be more efficacious with the addition of the PD-1 inhibitor cetrelimab, according to Sia Daneshmand, MD.1

Preliminary data from the study presented at the 2023 American Urological Association (AUA) Annual Meeting showed that evaluable patients treated with TAR-200 alone (n = 22) experienced a CR rate of 72.7% (95% CI, 49.8%-89.3%). In patients treated with cetrelimab alone (n = 21), the CR rate was 38.1% (95% CI, 18.1%-61.6%). Data for the cohort of patients who received the combination of TAR-200 and cetrelimab were immature at the time of this analysis.

“These preliminary results that are very encouraging. We hope that these [data] stand up later as we get more patients and longer duration of follow-up. We want to see durability,” Daneshmand said.

In an interview with OncLive®, Daneshmand discussed the rationale for investigating TAR-200 for the treatment of patients with BCG-unresponsive NMIBC, expanded on the preliminary efficacy and safety data from SunRISe-1, and previewed the next steps for evaluating TAR-200 in this patient population. Daneshmand is a professor of urology with clinical scholar designation, director of Clinical Research, and the director of the Urologic Oncology Fellowship at Keck Medicine of the University of Southern California (USC), in Los Angeles, California.

OncLive®: Could you expand on the rationale for investigating TAR-200 in patients with BCG-unresponsive NMIBC?

Daneshmand: There's a huge unmet need for patients with BCG-unresponsive disease. We haven't had much [movement] in terms of newly approved drugs in the past several decades. This is a large population of patients, and our options are fairly limited. [However], there are a number of trials and a number of agents coming out, which is great.

[This] unmet need was the rationale to try to see if we can improve on current treatment algorithms and try to decrease the number of cystectomies that are done in this patient population.

Could you provide some background on TAR-200 and cetrelimab?

TAR-200 was initially tested in a phase 1 trial [NCT02722538] that [had data] published in Urologic Oncology.2This phase 1 trial tested the safety and preliminary efficacy of this drug-eluting device that is placed inside of the bladder with gemcitabine mini tablets that are dissolved, and an asthmatic gradient is created within the urine. [There is] a port where the drug is released over a period of time.

In the initial phase 1 study, this was a neoadjuvant [treatment] given prior to radical cystectomy to [evaluate] the safety profile and preliminary efficacy. In the phase 1 trial, we saw a few complete responses [arm 1, n = 1/10; arm 2, n = 3/10] with photo documentation of tumors that were visible at time of cystectomy that had disappeared. There was an early signal [of efficacy], which prompted further study and entry into this next set of trials. The natural place for [TAR-200] would be the BCG-unresponsive space.

What key efficacy findings were reported from the SunRISe-1 trial at the 2023 AUA Annual Meeting?

The results have been exciting to see. These are the preliminary results of the SunRISe-1 study [investigating] TAR-200 [monotherapy], cetrelimab [monotherapy], and the combination of therapy with TAR-200 and cetrelimab in the BCG-unresponsive setting.

The results were not necessarily surprising, but [they were] very encouraging. I presented [data from] cohort 2 and cohort 3, which is TAR-200 alone and cetrelimab alone, [respectively]. We did not have enough evaluable patients in cohort 1, which was combination therapy [with TAR-200 and cetrelimab]. What we saw was in the TAR-200 alone arm, we had 22 patients evaluable at time of data cutoff. The [CR] rate was [72.7%]. These were CRs at any given time during the follow-up.

The rationale for cetrelimab alone was to see the efficacy of a PD-1 inhibitor. This is a novel PD-1 inhibitor that is like any other PD-1 inhibitor, and there weren't many surprises [in cohort 3]. That response rate was [38.1%], which is what we expected from monotherapy with an immuno-oncology [IO] agent in this setting, much like the pembrolizumab [Keytruda] data that we know is approved for the BCG-unresponsive carcinoma in situ.

Were there any data available from biomarker-enriched populations?

We don't have enough data right now to say anything about biomarker-enriched populations, and this was for all comers with BCG-unresponsive disease. There are further ongoing studies of the urine and other biomarkers.

What was seen in terms of the safety profile of each arm?

There were no surprises with the cetrelimab arm. We saw the usual adverse effects [AEs] that are seen with any kind of IO therapy. There were very few discontinuations with the IO therapy, as seen in prior trials with other IO agents.

TAR-200 was very well tolerated. Most of the patients retained [TAR-200 device] inside the bladder for up to 3 weeks. We saw the usual grade 1 and 2 AEs, and there were very few serious AEs of grade 3 and higher, so this is a well-tolerated device.

The systemic uptake of the drug was minimal to none. We were not seeing any systemic uptake, which was exactly what we wanted to see. The AEs are what we [typically] see in the management of any NMIBC agent.

Data from the phase 2 CORE-001 trial (NCT04387461) were also presented at the 2023 AUA Annual Meeting, showing clinical activity for CG0070 plus pembrolizumab in patients with BCG-unresponsive NMIBC.2 With promising results for a different approach for this patient population, how could this affect the treatment space down the line?

We're also seeing very good results in CORE-001. In the future, we're going to have an armamentarium of treatment options for these patients, and when they don't respond to one [treatment], perhaps they could go to the other. Availability and ease of use are going to factor into [treatment choices], but we would be happy to have more than 1 agent in the armamentarium for these patients.

What questions still need to be answered from SunRISe-1?

Can we reinduce patients if they do recur, if they responded the first time? Should we continue maintenance therapy? Do we need the IO [agent], or could we just use TAR-200 alone? Once we get more results from the combination therapy, we'll see if there is an additive effect of cetrelimab to TAR-200. There are data to come and [potential] future directions with this research.


  1. Daneshmand S, van der Heijden MS, Jacob JM, et al. First results from sunrise-1 in patients with BCG unresponsive high-risk non–muscle-invasive bladder cancer receiving TAR-200 in combination with cetrelimab, TAR-200, or cetrelimab alone. Presented at: 2023 AUA Annual Meeting. April 27-May 1, 2023; Chicago, IL. Abstract LBA02-03.
  2. Daneshmand S, Brummelhuis ISG, Pohar KS, et al. The safety, tolerability, and efficacy of a neoadjuvant gemcitabine intravesical drug delivery system (TAR-200) in muscle-invasive bladder cancer patients: a phase I trial. Urol Oncol. 2022 Jul;40(7):344.e1-344.e9. doi:10.1016/j.urolonc.2022.02.009
  3. Li R, Steinberg G, Uchio EM, et al. Phase 2 single arm study of CG0070 combined with pembrolizumab in patients with non muscle invasive bladder cancer unresponsive to bacillus Calmette-Guerin (BCG). Presented at: 2023 AUA Annual Meeting; April 28-May 1, 2023; Chicago, IL. Abstract PD13-08.
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