TAR-200 and cetrelimab nearly double response rate in muscle-invasive bladder cancer

Johnson & Johnson has revealed promising interim results from its ongoing Phase 2 SunRISe-4 study. This research focuses on the effectiveness of neoadjuvant treatment with TAR-200 combined with cetrelimab (CET) for patients with muscle-invasive bladder cancer (MIBC) who are either ineligible for or have refused neoadjuvant platinum-based chemotherapy and are scheduled for radical cystectomy (RC). These findings were presented at the European Society of Medical Oncology (ESMO) 2024 Congress.

The interim analysis of the study showed that the combination of TAR-200 plus CET achieved a nearly doubled pathological complete response (pCR) rate compared to CET alone. Specifically, the pCR rate was 42 percent for those treated with both TAR-200 and CET, versus 23 percent for those treated with CET alone. Additionally, the pathological overall response (pOR) rate, which indicates the proportion of patients with minimal residual disease (≤ pT1), was 60 percent for the combination therapy compared to 36 percent for CET alone.

In a subgroup analysis focusing on patients with organ-confined disease (cT2), the combined treatment showed a 48 percent pCR rate, compared to 23 percent for CET alone. Moreover, 68 percent of patients in this subgroup were downstaged (≤ pT1) at the time of their radical cystectomy. This suggests the potential for improved surgical outcomes and a reduced risk of recurrence.

Dr. Andrea Necchi from Italy's Vita-Salute San Raffaele University, a lead author of the study, emphasized that these are the first findings to show that an intravesical treatment with TAR-200 and a systemic PD-1 inhibitor (CET) could lead to a complete pathological response in a significant proportion of patients, while also being tolerable.

Dr. Kiran Patel, Vice President of Clinical Development for Solid Tumors at Johnson & Johnson, highlighted the potential of TAR-200 plus cetrelimab to change the pre-surgical treatment landscape for bladder cancer, offering an alternative for patients not eligible for standard pre-operative treatments.

However, treatment-related adverse events (TRAEs) were more common in patients receiving the combined therapy, occurring in 72 percent versus 44 percent for CET alone. Most of these adverse events were Grade 1-2. Nine percent of patients discontinued TAR-200 due to TRAEs, and eight percent discontinued CET in the combination therapy group. No discontinuations due to TRAEs occurred with CET alone.

Bladder cancer ranks as the ninth most common cancer globally. Despite the longstanding use of BCG immunotherapy, a significant proportion of patients (30-40 percent) do not respond and face recurrent or progressive disease, often necessitating radical cystectomy. This major surgery involves the removal of the bladder and nearby organs, requiring a urinary diversion post-operation.

TAR-200 is an investigational drug delivery system designed to release gemcitabine directly into the bladder over an extended period. The device can be installed in a brief, non-anesthesia procedure. In December 2023, TAR-200 received Breakthrough Therapy Designation from the FDA for potential use in patients with BCG-unresponsive high-risk non-muscle-invasive bladder cancer (HR-NMIBC) who are ineligible or have opted not to undergo radical cystectomy.

The SunRISe-4 study is an open-label, multicenter, randomized Phase 2 trial evaluating the efficacy and safety of neoadjuvant TAR-200 combined with CET, or CET alone, in patients with MIBC scheduled for RC. TAR-200 and CET are being investigated in various combinations across several clinical trials to assess their safety and efficacy in treating bladder cancer and other malignancies.

Cetrelimab is an investigational monoclonal antibody targeting the programmed cell death receptor-1 (PD-1) and is being studied in combination with other therapies for treating bladder cancer, prostate cancer, melanoma, and multiple myeloma.

Muscle-invasive bladder cancer (MIBC) is a serious condition where the cancer penetrates the muscular layer of the bladder, increasing the risk of metastasis. Approximately 25 percent of bladder cancer cases are diagnosed as MIBC upon initial presentation, making early detection and timely intervention crucial to managing the disease effectively.