Direct-to-Bladder Immunotherapy Drug to Be Studied in Bladder Cancer

The first patient with recurrent non-muscle invasive bladder cancer received treatment with lerapolturev in the phase 1/2 LUMINOS-103 clinical trial, according to Istari Oncology, the manufacturer of the novel drug.

LUMINOS-103 is a basket trial, meaning that researchers are evaluating lerapolturev-containing regimens in a variety of cancer types. For this particular study, lerapolturev will be investigated with or without PD-L1 inhibitors in adults with solid tumors.

The goal of the bladder cancer portion of the trial is to test the intravesical instillation (injected directly into the bladder) of lerapolturev, and how well it can infect tumor cells. Researchers will be looking at the proportion of patients who undergo cystectomy (bladder removal) or tumor resection as scheduled, as well as the safety and tolerability of lerapolturev.

Lerapolturev is an immunotherapy agent that targets poliovirus receptor CD155, which is commonly expressed on solid tumor cells. Through binding with that protein, lerapolturev works in three ways:

• Engaging and activating antigen-presenting cells, priming T cells to find and fight cancer
• Killing tumors directly, and releasing antigens
• Boosting the immune response by recalling polio vaccine-specific T cells

“We know that (non-muscle invasive bladder cancer) tissue expresses the poliovirus receptor, CD155 and is responsive to immunotherapy, providing the rationale for intravesicular lerapolturev for patients with low to intermediate risk BCG-naïve (disease),” said Dr. W. Garrett Nichols, chief medical officer at Istari Oncology, in a press release.

Even after patients undergo resection, bladder cancer will oftentimes come back, highlighting the need for a presurgical drug that can prevent recurrences, according to Nichols.

“Approximately 60,000 patients with low to intermediate risk (non-muscle invasive bladder cancer) are identified each year in the US alone; these patients could benefit from a well-tolerated immunotherapy such as lerapolturev as a replacement for repeat resections and intravesicular chemotherapy,” Nichols said.

Dr. Neal Shore, the study’s principal investigator and directory of the Carolina Urologic Research Center agreed.

“This is a largely unaddressed population of (non-muscle invasive bladder cancer) patients that, if we can identify and intervene early and effectively with a therapy like lerapolturev, can avoid progression and repeated surgeries or treatment with BCG, which has experienced severe shortages,” he said in the release.

Researchers plan on completing the study in May 2025.

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