Phase 3 Study of TAR-200/Cetrelimab Is Discontinued in MIBC

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The phase 3 SunRISe-2 trial (NCT04658862) evaluating the combination of TAR-200 and cetrelimab vs chemoradiation for the treatment of patients with muscle-invasive bladder cancer (MIBC) not undergoing radical cystectomy is being discontinued, according to an announcement from Johnson & Johnson.¹

The decision to halt the trial followed a prespecified interim analysis of the study and a recommendation from the trial’s independent data monitoring committee.

“Based 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,” Johnson & Johnson wrote in a news release. “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 (NCT04640623)] in non-MIBC in early 2025, with the [phase 3] SunRISe-3 [NCT05714202] and SunRISe-5 [NCT06211764] studies underway.”

Findings from SunRISe-4 showed that neoadjuvant treatment with TAR-200 plus cetrelimab elicited a pathologic complete response rate of 42% (95% CI, 28%-56%) and a pathologic overall response rate (ORR) of 60% (95% CI, 46%-74%) in patients with cT2 to CT4a MIBC who are not eligible for or declined neoadjuvant cisplatin-based chemotherapy (n = 53).²

SunRISe-2 was a phase 3, randomized, multicenter trial evaluating TAR-200 and cetrelimab vs chemoradiation in patients at least 18 years of age with MIBC who were ineligible for or declined radical cystectomy.³ Key inclusion criteria consisted of an ECOG performance status of 0 to 2; adequate bone marrow, renal, and liver function; and thyroid tests within normal range. Adverse effects from prior surgery or treatment needed to resolve to less than grade 2 prior to enrollment.

Patients were excluded if they had urothelial carcinoma or another histological variant at any site outside of the urinary bladder; however, patients with Ta/T1/carcinoma in situ (CIS) of the upper urinary tract were allowed to participate if they were treated with complete nephroureterectomy more than 24 months prior to the study. Other key exclusion criteria consisted of diffuse CIS per cystoscopy and biopsy; evidence of cT4b, or N1-3, or M1 disease; or any bladder or urethral anatomic feature that could prevent the safe placement, use, or removal of TAR-200.

Investigators randomly assigned patients to receive intravesical TAR-200 once every 3 weeks for the first 18 weeks, then every 12 weeks through year 3, plus intravenous cetrelimab; or chemotherapy consisting 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. Radiotherapy could be given at a dose of 64 Gy for up to 6.5 weeks or hypofractionated radiotherapy at 55 Gy for up to 4 weeks.

Bladder-intact event-free survival served as the trial’s primary end point. Secondary end points included 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://www.jnj.com/media-center/press-releases/johnson-johnson-statement-on-the-sunrise-2-study
2. 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
3. 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