DOC1021 Cell-based Immunotherapy in Combination With Standard Chemoradiation for Adjuvant Therapy of Glioblastoma: Early Results From an Expanded Access Protocol of a Phase I Trial
Jay-Jiguang Zhu1, Yoshua Esquenazi1, Sigmund H Hsu1, Mia Vu1, Rodrick Zvavanjanja2, Akshar Trivedi3, Wei Liu3, madhuri namekar4, Keenan Ernste3, Nitin Tandon1, Eva Schumann5, Elizabeth Duus5, Laura Aguilar5, Joseph Georges6, Vanaja konduri4, William Decker3
1Neurosurgery, 2Radiology, Univ of Texas Health Science Center in Houston, 3Baylor College of Medicine, 4Pathology & Immunology, Baylor College of Medicine, 5Diakonos Oncology, 6Neurosurgery, Banner Health
Objective:
To report ongoing results of an expanded access protocol evaluating DOC1021 in adult patients with new or recurrent glioblastoma.
Background:
Glioblastoma is a highly lethal malignancy with median overall survival of 12 months in real-world population studies using standard of care (SOC) therapies and ~14-21 months in clinical trial settings. DOC1021 is a dendritic cell (DC)-based immunotherapeutic derived from the full complement of autologous tumor antigens. It leverages p38MAPK and mTORC1 signaling cascades to initiate cDC1-like differentiation of monocyte-derived DCs, generating highly cytotoxic CD8+ memory effectors.
Design/Methods:
DOC1021 was prepared from mobilized peripheral blood mononuclear cells, loaded consecutively with autologous amplified tumor mRNA and tumor lysate. Following resection and chemoradiation, DOC1021 was injected bilaterally near the deep cervical node chains every other week for 3 doses (36 x 106 total cells), administered concurrently with 6 weekly doses of interferon. Patients were treated from November 2024 through July 2025, and follow-up is ongoing.
Results:
Seven patients (5 newly diagnosed, 2 recurrent) received all 3 planned doses of DOC1021 after surgical resection and SOC (median age: 57.0 years; 5/7 MGMT unmethylated). The most common DOC1021-related adverse events were mild injection site reactions. One patient developed grade 3 cerebral edema after the first DOC1021 dose, recovered, and completed subsequent doses as planned, reflecting a transient treatment-emergent immune response and/or aggressive dexamethasone taper. At the time of this analysis, all patients remain alive, with post-operative survival from the time of second surgery of 13 and 18 months for the first recurrent 2 patients and ongoing for the newly diagnosed cohort. Exploratory correlative studies are also ongoing.
Conclusions:
Administration of DOC1021 after resection and SOC is safe, feasible, and potentially efficacious in patients diagnosed with glioblastoma, confirming Phase I trial results. A multi-center, randomized, open-label Phase 2 trial for newly diagnosed glioblastoma patients (NCT06805305) is now enrolling.
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