Pooled analysis of phase I and expanded access study cohorts of DOC1021 (dubodencel) in combination with chemoradiation for glioblastoma.

2076 Background: Glioblastoma (GBM) is a poor-prognosis brain malignancy with median overall survival (mOS) of ~12-18 months despite aggressive standard of care (SOC) treatment. DOC1021 is an autologous dendritic cell (DC)-based immunotherapy generated by tandem loading with autologous tumor-derived mRNA and lysate, enabling broad antigen presentation. DOC1021 leverages p38MAPK and mTORC1 signaling cascades to initiate cDC1-like skewing of monocyte-derived DC, leading to potent downstream development of CD8 + tissue-homing, cytolytic effector memory cells. Methods: This pooled analysis includes newly diagnosed and recurrent IDH-wt patients from two clinical trials (Phase I Study 8148 [NCT04552886] and Expanded Access Protocol EAP0001), treated with DOC1021 after resection and SOC chemoradiation. DOC1021, prepared from mobilized peripheral blood mononuclear cells (PBMC) loaded consecutively with autologous amplified tumor mRNA and tumor lysate, was administered bilaterally near deep cervical lymph node chains every other week for 3 administrations with weekly pegylated-IFN. Study 8148 (n=18) evaluated 4 dose levels (3.5 x 10 6 to 36 x 10 6 cells), while Study EAP0001 (n=7) administered only the highest dose level (36 x 10 6 cells). Patients with subtotal resection or pre-treatment progression were not excluded. Blood was collected before and after DOC1021 to assess peripheral immune responses. Results: Among the pooled population (N=25), median age was 58 years (range 47-75), 88% MGMT unmethylated, 24% partially resected, and 16% recurrent disease. There were no dose-limiting toxicities, and a similar safety profile between studies. Common AEs included mild, flu-like symptoms and injection-site reactions. One patient in the EAP study experienced grade 3 cerebral edema after the first DOC1021 dose that fully resolved and subsequent DOC1021 doses were completed per protocol. At the time of analysis, 7 of 21 newly diagnosed patients remain alive ~9-30 months post-surgery. Among recurrent patients (n=4), 2 patients remain alive ~16-20 months after second resection. Pseudo-progression within ~6 months of vaccination was commonly observed. Analysis of post-vaccination PBMC indicated expansion of CD4 + (17/20 patients, mean +28.6%, p=0.0006) and CD8 + (15/20 patients, mean +26.8%, p=0.001) central memory T-cell (T CM ) compartments as well as substantial upregulation of CD127 expression on circulating CD8 + T cells (18/20; mean MFI +72.2%, p=0.03). Conclusions: Collectively, the data show that DOC1021 plus SOC is well-tolerated, feasible, and potentially efficacious in a challenging population that included subtotal resections, pre-treatment progression, and majority MGMT unmethylated. A multi-center, randomized, open-label Phase 2 trial (NCT06805305) in newly diagnosed GBM is now enrolling to compare DOC1021+SOC vs SOC treatment alone. Clinical trial information: NCT04552886 .