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LUMINOS-103 substudy of lerapolturev in NMIBC begins

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Lerapolturev will be given via intravesicular instillation to adult patients with recurrent NMIBC intended for transurethral resection of bladder tumor (TURBT) or cystectomy.

The treatment targets the poliovirus receptor CD155, which is widely expressed in the neoplastic cells of most solid tumors.

The treatment targets the poliovirus receptor CD155, which is widely expressed in the neoplastic cells of most solid tumors.

Lerapolturev (PVSRIPO) monotherapy via intravesicular instillation has been given to the first patient in a non–muscle-invasive bladder cancer (NMIBC) substudy of the LUMINOS-103 basket trial, Istari Oncology, the developer of the treatment, announced in a news release.1

“Approximately 60,000 patients with low- to intermediate-risk NMIBC 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,” W. Garrett Nichols, MD, MS, Chief Medical Officer at Istari Oncology, said in the news release.

Lerapolturev is an investigational immunotherapy developed from the live attenuated Sabin type 1 polio vaccine, which was genetically modified for safety. The treatment targets the poliovirus receptor CD155, which is widely expressed in the neoplastic cells of most solid tumors. By recalling the polio vaccine specific T-cells, lerapolturev amplifies the body’s immune response. In addition, the treatment engages and activates antigen presenting cells (APCs) to provide sustained immunity, and directs killing of tumor cells and antigen release.

LUMINOS-103 is a phase 1/2 open-label, single-arm basket trial (NCT04690699) evaluating the administration of lerapolturev with or without combination with anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) monoclonal antibody inhibitors in patients with advanced solid tumor cancers.2 The substudy of the trial is focusing on the treatment in adult patients with recurrent NMIBC intended for transurethral resection of bladder tumor (TURBT) or cystectomy.

Participants will receive lerapolturev by intravesicular instillation to test the ability of the treatment to infect tumor cells and infiltrate APCs within tumor tissue lining the bladder mucosa. The primary end point for the study is the proportion of patients who undergo TURBT as scheduled in a 1-month time frame. If safety and tolerability measures are met, phase 2 of the study will include patients with low- to intermediate-risk BCG-naïve disease.

“We know that NMIBC 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 NMIBC,” said Nichols.

The FDA granted lerapolturev breakthrough therapy and orphan drug designation status in recurrent glioblastoma (rGBM). Two phase 2 trials are currently underway to evaluate lerapolturev in patients with rGBM, and another trial is evaluating the treatment with or without immune checkpoint blockade in patients with advanced anti-PD-1 refractory melanoma.3 Now, investigators at the Carolina Urologic Research Center in Myrtle Beach, South Carolina are focusing on the treatment in NMIBC.

“We’re pleased to be the exclusive site for the NMIBC substudy. This is a largely unaddressed population of NMIBC 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,” said principal investigator Neal Shore, MD, in the news release. Shore is director of the Carolina Urologic Research Center.

Approximately 12 to 15 patients will be enrolled in the NMIBC substudy, which is still recruiting participants. The trial is expected to reach full enrollment by the middle of this year.

References

1. Istari Oncology announces first patient dosed in the non-muscle–invasive bladder cancer (NMIBC) substudy of the LUMINOS-103 basket trial evaluating lerapulturev monotherapy. News Release. Istari Oncology. Published online January 31, 2023. Accessed February 1, 2023. https://www.istarioncology.com/news-post/istari-oncology-announces-first-patient-dosed-in-the-non-muscle-invasive-bladder-cancer-nmibc-substudy-of-the-luminos-103-basket-trial-evaluating-lerapolturev-monotherapy

2. LUMINOS-103: A basket trial evaluating the safety and efficacy of lerapolturev (PVSRIPO) and lerapolturev in combination with anti-PD-1/L1 checkpoint inhibitors in patients with advanced solid tumor. ClinicalTrials.gov. Updated December 13, 2022. Accessed February 1, 2023. https://clinicaltrials.gov/ct2/show/NCT04690699

3. Clinical trials current status. Istari Oncology. Accessed February 1, 2023. https://www.istarioncology.com/clinical-trials/current-status

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