Johnson & Johnson has discontinued its Phase III SunRISe-2 trial evaluating TAR-200 in combination with cetrelimab for patients with muscle-invasive bladder cancer (MIBC) who are not undergoing radical cystectomy. The decision follows a recommendation from the independent data monitoring committee after a pre-specified interim analysis showed the treatment did not demonstrate superiority to chemoradiation.
The multi-center, randomized SunRISe-2 trial aimed to compare bladder intact-event free survival (BI-EFS) in participants receiving the combined treatment of TAR-200 and cetrelimab versus those undergoing standard chemoradiotherapy. Patients enrolled in the trial were MIBC patients not receiving radical cystectomy.
TAR-200 Development Continues in Other Bladder Cancer Studies
Despite the outcome of the SunRISe-2 trial, Johnson & Johnson remains optimistic about the potential of TAR-200 as a transformative therapy for bladder cancer, particularly in innovative and bladder-sparing approaches. Data from the Phase II SunRISe-4 study, presented at the 2024 ESMO Congress, indicated the potential of TAR-200 in MIBC.
According to a company statement, Johnson & Johnson is on track for a US Food and Drug Administration (FDA) filing of TAR-200 monotherapy based on data from the SunRISe-1 trial in non-muscle invasive bladder cancer, with a target date set for early next year. The company also confirmed that the SunRISe-3 and SunRISe-5 studies of TAR-200 are still in progress in participants with BCG-naïve high-risk non-muscle invasive bladder cancer (HR-NMIBC) and HR-NMIBC following Bacillus Calmette-Guérin (BCG), respectively.
SunRISe-4 Trial Shows Promise
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).
SunRISe-2 Trial Design
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. 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 randomly assigned 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.
