Muscle Invasive Bladder Carcinoma

Johnson & Johnson’s drug-device combo has disappointed in a late-stage test in people with an advanced form of bladder cancer, but it says it is still confident in the technology’s overall blockbuster potential. The company decided to stop the Phase 3 SunRISe-2 study because TAR-200 plus its PD-1 drug candidate cetrelimab did not show superiority to chemoradiotherapy at a pre-planned interim analysis, according to a release late Monday. The trial aimed to recruit around 550 patients with muscle-invasive bladder cancer who are not getting bladder removal surgery. TAR-200 consists of an old chemo product, gemcitabine, delivered in very low doses to the bladder through a silicone tube, or “pretzel,” over an extended period of time. The candidate has already passed a separate Phase 3 test called SunRISe-1 in non-muscle invasive bladder cancer, with 83% of treated patients achieving a complete response at three months’ follow-up. The company is set to file those monotherapy data with the FDA early next year. J&J obtained the technology behind TAR-200 during its buyout of Taris Biomedical in 2019. “We remain confident in the TARIS platform having $5B+ potential,” J&J said in a statement. The tech from Taris is also being deployed in a separate bladder cancer asset called TAR-210, which is designed for sustained local release of fibroblast growth factor receptor inhibitor erdafitinib. In May, results from a Phase 1 trial showed that 90% of high-risk non-muscle invasive bladder cancer patients given TAR-210 did not see their cancer recur at the one-year mark. As for TAR-200, the candidate is being evaluated alone and in combination with three other Phase 3 studies in various settings of bladder cancer: SunRISe-3 , SunRISe-4 and SunRISe-5 .

Researchers from the Institute of Cancer Research (ICR) have highlighted the potential benefits of treating bladder cancer with personalised radiotherapy. More than 130,000 patients are treated on the NHS every year with radiotherapy, which works by targeting tumours with X-ray radiation. However, the current use of the treatment usually involves a ‘one size fits all’ approach, in which the dosage is the same in each session. Published in the journal European Urology , the phase 2 RAIDER study was designed to find out whether muscle-invasive bladder cancer can be treated with adaptive radiotherapy, a method that involves changing the volume of radiotherapy depending on the area of the body being targeted. The researchers split 345 patients into one of three groups. Patients in the first group received the same treatment plan in each session, while those in the other two were given one of a number of treatment plans, determined on a case-by-case basis in each session. The researchers found that there were fewer serious long-term side effects six to 18 months after treatment than those reported in previous studies across all three groups, with no evidence that those who received higher dose treatment had any worse side effects compared with those who received standard radiotherapy treatment. Approximately 10,500 new cases of bladder cancer are diagnosed in the UK every year. Healthcare workers face a number of challenges treating the disease and the changing shape and position of the bladder can create complications when delivering targeted radiotherapy. The work was funded by Cancer Research UK, Cancer Australia and the Cancer Society of New Zealand, and also supported by the National Institute of Health and Care Research Biomedical Research Centre at The Royal Marsden NHS Foundation Trust. Robert Huddart, professor of urological cancer and honorary consultant clinical oncologist at the Royal Marsden and group leader at the ICR said: “Delivering radiotherapy to the bladder is a challenging process. We are pleased this work into a potential new way of treating bladder cancers has allowed us to deliver effective treatment safely and allowed us to use a high dose which promises to cure more patients, with relatively few long-term side effects. “We look forward to studying this method further to explore its effectiveness versus current treatment options.”

Johnson & Johnson has decided to discontinue its SunRISe-2 study, which was testing a new approach for treating muscle-invasive bladder cancer (MIBC) in patients who aren’t having a radical cystectomy. The move follows a recommendation from an independent data monitoring committee after an interim analysis showed that the study didn’t outperform standard chemoradiation. Even though the study didn’t go as planned, the company says it remains confident in TAR-200, its bladder cancer therapy. Data from the SunRISe-4 study, presented at the 2024 European Society for Medical Oncology Congress, showcased TAR-200’s potential to offer bladder-sparing treatment options, something critically needed for MIBC patients. Johnson & Johnson is still on track to file for U.S. FDA approval of TAR-200 as a monotherapy for non-muscle invasive bladder cancer in early 2025. Meanwhile, the SunRISe-3 and SunRISe-5 studies are ongoing. The company also says it continues to back the TARIS platform, projecting it could generate more than $5 billion in annual peak sales.