Longitudinal stereotactic injections of oncolytic immunoactivating rQNestin34.5v.2 (CAN-3110) with concomitant biopsies for “-omic” analyses in recurrent glioblastoma (GBM).

person David A. Reardon Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA info_outline David A. Reardon

Authors person David A. Reardon Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA info_outline David A. Reardon Organizations Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA Abstract Disclosures Research Funding No funding sources reported Background: Glioblastoma (GBM), the most common primary malignant brain tumor remains incurable. Numerous clinical trials of highly promising treatment modalities have not met efficacy objectives to support regulatory approval. One limitation in trial evaluation has been the lack of tumor sampled at various timepoints during therapy to allow analyses of the treatment’s effect. Sequential biopsies have not been pursued due to possible morbidity, relative surgical inaccessibility of GBM within the brain, and quality and quantity of stereotactic biopsies to permit detailed analyses. We hypothesized that the convergence of modern neurosurgical techniques and imaging with sophisticated “omics” analyses would overcome these limitations. Methods: A multi-institutional phase 1 clinical trial was started in recurrent GBM (rGBM) patients treated with up to 6 stereotactic administrations of the oncolytic immunotherapy, rQNestin34.5v.2 (CAN-3110) (Ling et al. Nature , 2023) over 4 months (day 0, 15, 30, 60, 90 and 120) with concomitant multisector biopsies. Two cohorts of 1 x10 8 pfu per injection and 1 x 10 9 pfus per injection of rQnestin34.5v.2 are planned for a total of 6 patients per cohort using a Bayesian optimal interval (BOIN) design for dose escalation. Before each injection, multiregional sector biopsies of rGBM are undertaken and the biopsies are processed for “-omic” analyses, including single cell RNA sequencing, proteomics/phosphoproteomic/immunopeptidomics, metabolomics, spatial transcriptomics and cell profiles as well as other technologies. In addition, concomitant CSF and blood analyses are performed at the same time to longitudinally correlate biofluid markers with the treated rGBM tissues. So far, 6 patients have accrued, completing cohort 1 without experiencing DLT or SAE from the injected oncolytic rQNestin34.5v.2 and/or the multiple longitudinal procedures. A total of 316 longitudinal core biopsies were obtained from all 6 patients across the planned timepoints. The biopsies have been successfully processed for ongoing longitudinal scientific “-omic” data for the first 2 patients. Cohort 2 is scheduled to start enrollment in the spring of 2024 (NCT03152318). This abstract is submitted on behalf of the Break Through Cancer Accelerating Glioblastoma Therapies Team Lab (breakthroughcancer.org). Clinical trial information: NCT03152318.

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