Trls-11. Pnoc005: Oncolytic Measles Virus for the Treatment of Children and Young Adults With Recurrent Medulloblastoma or Atypical Teratoid Rhabdoid Tumor
Year: 2024
Type: conference-abstract
Abstract: BACKGROUND PNOC005 is a phase 1 clinical trial investigating the safety and tolerability of intratumoral or intrathecal administration of oncolytic measles virus (MV-NIS) in children and young adults with recurrent medulloblastoma (MB) or atypical teratoid/rhabdoid tumor (ATRT). METHODS Patients with recurrence of MB or ATRT were stratified into Stratum A (local recurrence) or B (disseminated recurrence). Stratum A patients received MV-NIS directly into the tumor bed at time of surgical resection. Stratum B patients received a single dose of MV-NIS via lumbar puncture. After safety was demonstrated in Stratum A and B, Stratum C was added with repeat dosing on Day 0 and 7 for patients with recurrent disseminated MB. Specimens for viral shedding were collected. Blood was collected on days 0, 4, 7, 14, and 28. RNA-sequencing deconvolution and time-series analysis were performed to estimate the composition and phenotypes of peripheral blood mononuclear cells (PBMCs). RESULTS Thirty-four patients (median age 8.5, range 2-31) enrolled between February 2017 and April 2021, with 23 evaluable patients with MB and 4 with ATRT. One patient experienced a dose-limiting toxicity (grade 3 alanine aminotransferase increase). There were four MV-NIS-related adverse events grade 3 or greater across all strata. Viral shedding was detected in 5 patients, all of which cleared by end-of-treatment. We found a similar gene-expression program in PMBCs that correlated across patients (n=18), which was upregulated at days 4-7 post treatment and consistent with an antiviral response. Concomitant changes in B, T, and natural-killer cell composition and activation were consistent with this interpretation. CONCLUSION This is the first trial investigating intratumoral as well as repeated intrathecal delivery of MV-NIS in children with MB and ATRT. We show that therapy is safe and well-tolerated with minimal adverse effects. Immune markers and biologic correlates preliminarily indicate anti-viral effects in tumors.
Source: Neuro-Oncology
Authors: Cassie Kline, Bohyeon Yu, Truman Knowles, Aeesha Ranavaya, Jane Minturn, Anuradha Banerjee, Sarah Leary, Mohamed Abdelbaki, Nicholas Whipple, Stewart Goldman, Ashley Margol, Nour Dababo, Andreas Rauschecker, Elizabeth George, Ali Nabavizadeh, Owen Hoare, Jangham Jung, Joanna Phillips, Michael Prados, Annette Molinaro, Nalin Gupta, Corey Raffel, Kristina Cole, Aaron Diaz, Sabine Mueller
Institutions: Children's Hospital of Philadelphia, University of Pennsylvania, University of California, San Francisco, Seattle Children's Hospital, University of Washington, St. Louis Children's Hospital, Washington University in St. Louis, Primary Children's Hospital, University of Utah, Phoenix Children's Hospital, University of Arizona College of Medicine- Phoenix, University of Southern California, Children's Hospital Los Angeles, University Children's Hospital Zurich
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $5,389
OpenAlex ID: W4399787331