{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T12:17:18Z","timestamp":1792671438340,"version":"4.5.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2025,3,22]],"date-time":"2025-03-22T00:00:00Z","timestamp":1742601600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>For newly diagnosed glioblastoma (GBM), a combination of upfront surgical immunotherapy with aglatimagene besadenovec (CAN-2409), followed by chemoradiation and then adjuvant nivolumab has not been tested. The aim of this study was to test the safety of this regimen and determine metrics of immune activation that may correlate with clinical outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Forty-one patients with suspected newly diagnosed GBM by imaging were enrolled in this multi-institutional, open-label, phase 1b clinical trial before surgical resection. Frozen section confirmation of high-grade glioma was required for administration of CAN-2409. This was then followed with chemoradiation and adjuvant nivolumab. Tumor and blood were assayed for genetic and immune markers before and during treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The regimen was well tolerated and generated measurable immune activation. Factors linked to survival were identified, such as baseline mutated gene pairs (eg, MED15\/HRC), tumor immune cell composition, and changes in systemic cytokine, immune cells, and T-cell diversity. The most significant serial systemic immune changes were observed in a long-term survivor subset of patients with gross total resection (GTR)\/methylated methylguanine methyltransferase (MGMT) promoter tumors. Median overall survival (mOS) in these patients was 30.6 months, while it was less for patients with unmethylated or subtotal resections.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings suggest the opportunity for patient stratification and the potential for more durable antitumor immune responses in future clinical trials of this multimodal standard of care and combined immunotherapy regimen. ClinicalTrials.gov identifier: NCT03576612.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/neuonc\/noaf079","type":"journal-article","created":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T16:20:33Z","timestamp":1742228433000},"page":"2617-2631","source":"Crossref","is-referenced-by-count":12,"title":["A multi-institutional phase 1 clinical trial exploring upfront multimodal standard of care and combined immunotherapies for newly diagnosed glioblastoma"],"prefix":"10.1093","volume":"27","author":[{"given":"Patrick Y","family":"Wen","sequence":"first","affiliation":[{"name":"Adult Brain Tumor Consortium , Baltimore, Maryland ,","place":["USA"]},{"name":"Center for Neuro-oncology, Dana-Farber Cancer Institute , Boston, Massachusetts ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Manzanera","sequence":"additional","affiliation":[{"name":"Candel Therapeutics , Needham, Massachusetts 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