Data from the ongoing Phase 2 SunRISe-4 study was presented recently at ESMO 2024.

The study, featured as a late-breaking oral presentation, looked at neoadjuvant treatment with investigational TAR-200 plus cetrelimab (CET) for MIBC.

Results showed the combo achieved nearly double the pathological complete response (pCR) rate compared to CET alone in patients with muscle-invasive bladder cancer (MIBC) who are ineligible or refuse neoadjuvant platinum-based chemotherapy and scheduled for radical cystectomy (RC). 

"These findings from the SunRISe-4 study show for the first time that an intravesical treatment with TAR-200, combined with a systemic PD-1 inhibitor, could potentially result in a complete pathological response in a high proportion of patients, as well as allowing a tolerable approach," said Andrea Necchi, M.D., of Italy's Vita-Salute San Raffaele University and the IRCCS San Raffaele Hospital and Scientific Institute and a presenting author of the study.

"These preliminary findings show a potential for a future change in the local treatment of muscle-invasive bladder carcinoma using TAR-200."

In the interim analysis of the SunRISe-4 study, neoadjuvant TAR-200 plus CET (n=53) showed overall efficacy with a centrally confirmed pathologic complete response (pCR, [T0]) rate of 42 percent compared to 23 percent (95 percent CI, 28-56; 10-41, respectively) with CET alone (n=31) in patients with histologically proven, non-metastatic MIBC.

The pathological overall response (pOR) rate (defined as the proportion of patients ≤ pT1) was 60 percent compared to 36 percent, respectively (CI 95 percent, 46-74; 19-55).

In a subgroup analysis of patients with organ-confined disease (cT2), those treated with TAR-200 plus CET (n=40) showed a 48 percent pCR rate compared to 23 percent pCR with CET alone (n=26, 95 percent CI, 32-64; 9-44, respectively) and 68 percent were downstaged (≤ pT1) at the time of radical cystectomy, potentially improving surgical outcomes and reducing risk of recurrence.

"With these promising results, TAR-200 plus cetrelimab as a neoadjuvant therapy before radical cystectomy could potentially alter how bladder cancer is treated," said Kiran Patel, M.D., Vice President, Clinical Development, Solid Tumors, Innovative Medicine, Johnson & Johnson.

"This investigational innovative approach may offer a possible alternative for many patients who are not eligible for the current standard of pre-operative treatments."

Treatment-related adverse events (TRAEs) occurred in 72 percent of patients treated with TAR-200 combined with CET and 44 percent of patients treated with CET alone, with the majority being Grade 1-2.

Nine percent of patients discontinued treatment with TAR-200 and eight percent discontinued treatment with CET in the combined treatment cohort due to TRAEs; no patients discontinued treatment due to TRAEs when treated with CET alone.

Bladder cancer is the ninth most common cancer in the world. 

Although BCG immunotherapy has been accepted as the standard of care for nearly five decades, 30-40 percent of patients do not respond to BCG and experience disease recurrence or progression.

In such scenarios, radical cystectomy (removal of the bladder and neighbouring structures and organs) emerges as the primary treatment option.

This major abdominal procedure requires a urinary diversion to be created to collect and store urine.

TAR-200 is an investigational targeted releasing system designed to provide extended local release of gemcitabine into the bladder.

It is installed in a physician's office setting during a 2-3 minute procedure with no anaesthesia.

In December 2023, the FDA granted TAR-200 Breakthrough Therapy Designation (BTD) for the potential future treatment of patients with BCG-unresponsive HR-NMIBC, who are ineligible for or elected not to undergo radical cystectomy (surgical removal of the bladder).

Source: Johnson & Johnson