{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T22:37:49Z","timestamp":1793227069636,"version":"4.5.0"},"reference-count":39,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"27","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2025,9,20]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>\n                      New therapies for glioblastoma are needed, especially\n                      <jats:italic toggle=\"yes\">MGMT<\/jats:italic>\n                      -unmethylated (u\n                      <jats:italic toggle=\"yes\">MGMT<\/jats:italic>\n                      ) disease. NRG Oncology BN002 (phase I) demonstrated safety and suggested efficacy of ipilimumab (ipi) with nivolumab (nivo) in newly diagnosed glioblastoma, leading to this phase II\/III trial.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      Adults with newly diagnosed u\n                      <jats:italic toggle=\"yes\">MGMT<\/jats:italic>\n                      glioblastoma and Karnofsky performance status (KPS) \u226570 were randomly assigned to radiotherapy with either immunotherapy (ipi and nivo) or temozolomide (TMZ), stratified by recursive partitioning analysis (RPA) class and intention to use tumor treating fields. With 95% power to detect a hazard ratio (HR) \u22640.58 for progression-free survival (PFS) at a one-sided significance level (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      ) of .15, superior PFS with immunotherapy in phase II would lead to phase III overall survival (OS) testing. Corticosteroids were disallowed when starting immunotherapy. Diagnosis, biomarkers, and PFS were centrally assessed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      One hundred fifty-nine participants were randomly assigned (79 immunotherapy and 80 TMZ). Arms were well balanced for age (median 60 years, range, 28-79), sex (male n = 105, 66%), KPS (90-100 n = 97, 61%), resection extent (gross total, n = 103, 65%), and RPA class (III, n = 16, 10%; IV, n = 116, 73%; V, n = 27, 17%). A preplanned analysis of phase II data conducted after 100 centrally determined PFS events showed no significant PFS improvement for ipi and nivo versus TMZ (median 7.7 months\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      8.5 months, HR, 1.47 [70% CI, 1.19 to 1.83]; one-sided\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .96 [95% CI, 0.98 to 2.2]). OS is immature (&gt;50% alive) but with no observed difference between arms (median approximately 13 months each, HR, 0.95 [95% CI, 0.61 to 1.49];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .36).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      Ipi and nivo did not improve PFS among patients with newly diagnosed u\n                      <jats:italic toggle=\"yes\">MGMT<\/jats:italic>\n                      glioblastoma versus TMZ. Accrual closed permanently; the trial will not proceed to phase III. No new safety signals were identified. Molecular correlative analyses and survival follow-up are ongoing.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-25-00618","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T19:59:26Z","timestamp":1754683166000},"page":"3032-3040","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":36,"title":["Dual Immune Check Point Blockade in\n                    <i>MGMT<\/i>\n                    -Unmethylated Newly Diagnosed Glioblastoma: NRG Oncology BN007, a Randomized Phase II\/III Clinical Trial"],"prefix":"10.1200","volume":"43","clinical-trial-number":[{"clinical-trial-number":"nct04396860","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7386-9928","authenticated-orcid":true,"given":"Andrew B.","family":"Lassman","sequence":"first","affiliation":[{"name":"Division of Neuro-Oncology, Department of Neurology, Columbia 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