TAR-200 Study in Muscle-Invasive Bladder Cancer Discontinued

Currently, TAR-200 is being assessed in the phase 2 SunRISe-4 trial (NCT04919512) for MIBC and the SunRISe-3 and 5 trials for non-MIBC.

The phase 3 SunRISe-2 trial (NCT04658862) has been discontinued, in which TAR-200 plus cetrelimab vs chemoradiation was being assessed in patients with muscle-invasive bladder cancer (MIBC), according to a press release from Johnson & Johnson.¹

Specifically, TAR-200 did not show superior benefits compared with chemoradiation. TAR-200 plus cetrelimab was used to test the period from the start of treatment until the patient no longer had certain complications like cancer or death.

An independent data monitoring committee recommended the trial discontinuation.

Currently, TAR-200 is being assessed in the phase 2 SunRISe-4 trial (NCT04919512) for MIBC and the SunRISe-3 and 5 trials for non-MIBC.² At the 2024 European Society for Medical Oncology Congress, data from SunRISe-4 were presented.³

Findings from the trial showed TAR-200 plus cetrelimab led to a pathological complete response (pCR) rate of 42% (95% CI, 28%-56%) and a pathological overall response (pOR) rate of 60% (95% CI, 46%-74%). In the cetrelimab monotherapy arm, the pCR rate was 23% (95% CI, 10%-41%), and the pOR rate was 36% (95% CI, 19%-55%).

The subgroup analysis showed patients with organ-confronted disease given TAR-200 plus cetrelimab had a pCR of 48% (95% CI, 32%-64%) vs 23% (95% CI, 9%-44%) in the monotherapy arm.⁴ At the time of radical cystectomy, 68% of patients were downstaged, which potentially helped to improve surgical outcomes and reduced the risk of recurrence.

“SunRISe-4 demonstrates for the first time a benefit of the addition of TAR-200, an intravesical targeted releasing system, to checkpoint inhibition as neoadjuvant treatment in patients with MIBC,” Andrea Necchi, MD, of IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, in Milan, Italy, said during the presentation.

The SunRISe-2 study was designed to evaluate the efficacy and safety of intravesical TAR-200 plus cetrelimab vs concurrent chemoradiotherapy for patients with MIBC who refuse or are not eligible for radical cystectomy.⁵ A total of 550 patients were planned to be enrolled. Currently, 382 patients were recruited from 176 sites.

Patients were included in the study if they had histologically confirmed cT2-T4a, N0 or M0 urothelial bladder carcinoma; a diagnosis within 90 days of randomization; an ECOG performance status of 0 to 2; and normal thyroid function and adequate bone marrow, live, and renal function.

Patients were excluded from treatment if they had urothelial carcinoma or histological variant of 20% or more outside of the urinary bladder; evidence of cT4b, N1-3, or M1 disease; or diffuse carcinoma in situ.

Patients were randomly assigned 1:1 and given intravesical TAR-200 every 3 weeks for the first 18 weeks, followed by every 12 weeks from week 24 through year 3 plus intravenous cetrelimab. Intravenous cisplatin every week for 4 to 6 weeks and gemcitabine were given as standard of care plus conventional radiation therapy at 64 Gy up to 6.5 weeks or hypofractionated radiotherapy at 55 Gy for up to 4 weeks.

The primary end point was bladder-intact event-free survival. Secondary end points included metastasis-free survival, overall response rate based on biopsy at week 18, overall survival, and safety and tolerability.

In the combination arm of the SunRISe-4 study, 72% of patients experienced treatment-related adverse effects (TRAEs) vs 44% in the monotherapy arm. The majority of these toxicities were grade 1/2. Treatment was discontinued in 9% of patients with TAR-200 vs 8% with cetrelimab in the combination arm because of TRAEs. When cetrelimab was used to treat patients as monotherapy, no patients discontinued treatment.

References

1. J&J discontinues late-stage study for bladder cancer. News release. Reuters. October 7, 2024. Accessed October 9, 2024. https://shorturl.at/tEIqJ
2. Johnson & Johnson statement on the SunRISe-2 study. News release. Johnson & Johnson. October 7, 2024. Accessed October 9, 2024. https://shorturl.at/Xal6M
3. Necchi A, Guerrero-Ramos F, Crispen PL, et al. TAR-200 plus cetrelimab or cetrelimab alone as neoadjuvant therapy in patients with muscle-invasive bladder cancer who are ineligible for or refuse neoadjuvant cisplatin-based chemotherapy: interim analysis of SunRISe-4. Presented at: 2024 ESMO Congress; September 13-17, 2024; Barcelona, Spain. Presentation LBA84.
4. Neoadjuvant TAR-200 plus cetrelimab nearly doubles the pathological complete response rate compared to cetrelimab alone in patients with muscle-invasive bladder cancer. News release. Johnson & Johnson. September 16, 2024. Accessed October 9, 2024. https://shorturl.at/RaQco
5. TAR-200. Janssen Sciences. Accessed October 9, 2024. https://shorturl.at/f1UN6