Phase I Analysis of DOC1021, A Cell-based Vaccination Platform for Adjuvant Therapy of Glioblastoma
Jay-Jiguang Zhu1, Yoshua Esquenazi2, Sigmund Hsu2, Rodrick Zvavanjanja3, Mia Vu2, Eva Schumann4, Akshar Trivedi5, Wei Liu5, Madhuri Shailesh Namekar5, Colby James Hofferek5, Keenan James Ernste5, Corey Mossop7, Christina Clay7, Sabina Amin7, Vinod Ravi8, Jan Kemnade9, Laura Aguilar4, Alan Turtz7, Nitin Tandon2, Vanaja Konduri5, Joseph Georges10, William Decker6
1Neurosurgery, Univ of Texas Health Science Center in Houston, 2Neurosurgery, 3Radiology, University of Texas Health Science Center at Houston, 4Diakonos Oncology, Corporate, 5Baylor College of Medicine, 6Department of Pathology & Immunology, Baylor College of Medicine, 7Cooper University Health Care, 8MD Anderson Cancer Center, 99University of Alabama Birmingham College of Medicine, 10Banner University Medical Center
Objective:
We report ongoing results of an open-label phase I trial in which DC vaccines prepared through homologous antigenic loading were administered to patients with newly diagnosed glioblastoma.
Background:
Glioblastoma is a devastating tumor with median survival of 14-18 months despite aggressive intervention. Cellular immunotherapies have previously shown promise but with inconclusive results. Homologous antigenic loading is a cutting-edge technology that initiates powerful cDC1-like skewing of monocyte-derived dendritic cells, leading to induction of tissue-infiltrating, cytolytic effector-memory T-cells.
Design/Methods:
Enrollment exclusion criteria were minimal but excluded IDH mutants. Progression prior to vaccination was not exclusionary. Vaccines were generated from mobilized peripheral blood and loaded with autologous tumor lysate and amplified tumor mRNA and were administered bilaterally in close proximity to the deep cervical node chains. Patients additionally received concurrent adjuvantation with type I interferon. Four dose levels from 3.5x106 to 3.6x107 vaccine cells were tested. Immune responses were evaluated by flow cytometry of peripheral blood and, in three patients, by spatial transcriptomics.
Results:
Sixteen newly diagnosed patients completed treatment, 94% (15/16) MGMT unmethylated. No AEs > grade 2 attributable to the investigational regimen, nor DLTs were observed. Analysis of post-vaccination PBMC indicated expansion of CD4+ (13/13) and CD8+ (11/13) central memory T-cell compartments (p<0.002 and p<0.05, respectively) as well as expansion of CD8+CD127+ MPECs (12/13; p<0.001). Among 3/3 patients analyzed by spatial transcriptomics, intense CD25+ foci that overlapping effector memory T-cell and migratory microglial markers were observed in post-vaccination samples only. One-year OS of the 15/16 unmethylated MGMT cohort was 88% in comparison to 53% of an age-matched control cohort (p<0.002) that contained historic numbers (~40%) of MGMT methylated patients (HR for death at 1 year = 0.33, 95% CI 0.14-0.78, p=0.1).
Conclusions:
The results suggest that DOC1021 is safe, immunogenic, potentially efficacious, and can be effectively integrated within existing standards of care.
Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff.