SunRISe-2 Study of TAR-200 Plus Cetrelimab in MIBC Discontinues

Following an interim analysis and recommendation from the independent data monitoring committee, the SunRISe-2 trial (NCT04658862) evaluating treatment with TAR-200 given in combination with cetrelimab vs chemoradiation in muscle-invasive bladder cancer (MIBC) not undergoing radical cystectomy has been discontinued.¹

In a press release, Johnson & Johnson wrote, “[b]ased on data presented, we are highly confident in TAR-200 as a transformative therapy for bladder cancer where innovative and bladder-sparing options are urgently needed.”

TAR-200 is an intravesical targeted release system that previously has shown potential in patients with non-muscle invasive disease with Bacillus Calmette-Guérin (BCG)-unresponsive disease, as demonstrated by recent data from the SunRISe-1 study (NCT04640623) presented at the 2024 American Urological Association Meeting.²

At the data cutoff date of January 2, 2024, 82.8% (95% CI, 70.6%-91.4%) of response-evaluable patients given TAR-200 as monotherapy (n = 58) achieved a centrally assessed complete response (CR), and 86.2% (95% CI, 74.6%-93.9%) achieved an investigator-assessed CR. The Kaplan-Meier estimates for CR rate at 6 and 12 months were 75.7% (95% CI, 59.1%-86.3%) and 61.9% (95% CI, 41.1%-77.1%), respectively, and 98% of CRs were achieved at the first disease assessment at week 12.

In the SunRISe-4 trial (NCT04919512), neoadjuvant treatment with TAR-200 plus cetrelimab led to a pathologic CR rate of 42% (95% CI, 28%-56%) and a pathologic overall response rate (ORR) of 60% (95% CI, 46%-74%) when given to patients with cT2 to CT4a MIBC who are not eligible for or declined neoadjuvant cisplatin-based chemotherapy (n = 53).³ Additionally, the safety profile of TAR-200 and cetrelimab was manageable, suggesting TAR-200 may be a promising treatment option for patients with MIBC, particularly patients with early-stage disease.

“Data from the [phase 2] SunRISe-4 study [NCT04919512] recently presented at the 2024 ESMO Congress show the potential of TAR-200 in MIBC, and we will continue to pursue approaches to advance care in this setting. We are on target for the United States FDA filing of TAR-200 monotherapy [based on data from the phase 2 SunRISe-1 trial] in non-MIBC in early 2025, with the [phase 3] SunRISe-3 [NCT05714202] and SunRISe-5 [NCT06211764] studies underway,” added Johnson & Johnson in the press release.¹

About the SunRISe-2 Trial

In the phase 3, randomized, multicenter SunRISe-2 study, experts sought to evaluate TAR-200 plus cetrelimab vs chemoradiation in patients at least 18 years of age with MIBC.⁴ Patients were required to be ineligible for or had declined radical cystectomy; have an ECOG performance status of 0 to 2; have adequate bone marrow, renal, and liver function; and have thyroid tests within normal range. Additionally, all adverse effects from prior surgery or treatment must have been resolved to less than grade 2 before enrollment.

Patients were randomly assigned to receive intravesical TAR-200 once every 3 weeks for the first 18 weeks. This was followed by treatment given every 12 weeks through year 3 with intravenous cetrelimab or chemotherapy, which consisted of investigator’s choice of cisplatin once per week for 4 to 6 weeks or gemcitabine twice per week for 4 to 6 weeks, in combination with radiation. Patients could receive radiotherapy at a dose of 64 Gy for up to 6.5 weeks or hypofractionated radiotherapy at 55 Gy for up to 4 weeks.

The primary end point of the study was bladder-intact event-free survival, and secondary end points were metastasis-free survival, overall survival, ORR, and safety.

REFERENCES:

1. Johnson & Johnson statement on the SunRISe-2 study. News release. Johnson & Johnson. October 7, 2024. Accessed October 8, 2024. https://tinyurl.com/3m9crbbx

2. Necchi A, Daneshmand S, Simone G, et al. TAR-200 in patients with Bacillus Calmette–Guérin-unresponsive high-risk non–muscle-invasive bladder cancer: results from SunRISe-1 study. J Urol. Published online May 1, 2024. doi:10.1097/01.JU.0001015816.87470.c9.01

3. Necchi A, Guerrero-Ramos F, Crispen PL, et al. TAR-200 plus cetrelimab (CET) or CET alone as neoadjuvant therapy in patients (pts) with muscle-invasive bladder cancer (MIBC) who are ineligible for or refuse neoadjuvant cisplatin-based chemotherapy (NAC): interim analysis of SunRISe-4 (SR-4). Ann Oncol. 2024;35(suppl 2):S1271-S1272. doi:10.1016/j.annonc.2024.08.2328

4. A study of TAR-200 in combination with cetrelimab versus concurrent chemoradiotherapy in participants with muscle-invasive bladder cancer (MIBC) of the bladder (SunRISe-2). ClinicalTrials.gov. Updated September 19, 2024. Accessed October 8, 2024. https://clinicaltrials.gov/study/NCT04658862