Abstract Details

Title Phase I Analysis of DOC1021, A Cell-based Vaccination Platform for Adjuvant Therapy of Glioblastoma

Topic Neuro-oncology

Presentation(s) S29 - Neuro-oncology (4:06 PM-4:18 PM)

Poster/Presentation
Number 004

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.

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.

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.

Authors/Disclosures
Jay-Jiguang Zhu, MD, PhD, FAAN (Univ of Texas Health Science Center in Houston) PRESENTER	The institution of Dr. Zhu has received research support from Novocure, Inc. The institution of Dr. Zhu has received research support from Five Prime pharmaceutical. The institution of Dr. Zhu has received research support from Denovo, inc. The institution of Dr. Zhu has received research support from Boston Biomedical Sumitomo Dainippon Pharma Global Oncology. The institution of Dr. Zhu has received research support from CNS pharmaceutical. The institution of Dr. Zhu has received research support from ABM Therapeutics Corporation . The institution of Dr. Zhu has received research support from Chimerix Inc.
Yoshua Esquenazi, MD	Dr. Esquenazi has nothing to disclose.
Sigmund H. Hsu, MD (New York Hospital)	No disclosure on file
Rodrick C. Zvavanjanja, MD	Dr. Zvavanjanja has nothing to disclose.
Mia Vu, CRC	Miss Vu has nothing to disclose.
Eva H. Schumann	Ms. Schumann has received personal compensation for serving as an employee of Diakonos Oncology.
Akshar J. Trivedi, MS	Mr. Trivedi has nothing to disclose.
Wei Liu, MD	Ms. Liu has nothing to disclose.
Madhuri S. Namekar, MSc MS	Mrs. Namekar has nothing to disclose.
Colby James Hofferek (Baylor College of Medicine)	No disclosure on file
Keenan Ernste	Mr. Ernste has received intellectual property interests from a discovery or technology relating to health care.
Corey Mossop, MD	Dr. Mossop has nothing to disclose.
Christina Clay, MD	Dr. Clay has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for law firm. Dr. Clay has stock in investment portfolio.
Sabina Amin, MD	Dr. Amin has nothing to disclose.
Vinod Ravi (MD Anderson Cancer Center)	No disclosure on file
Jan Kemnade, MD, PhD	Dr. Kemnade has nothing to disclose.
Laura Aguilar, MD, PhD	Dr. Aguilar has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Diakonos Oncology. An immediate family member of Dr. Aguilar has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Candel Therapeutics. Dr. Aguilar has stock in Candel Therapeutics .
Alan Turtz, MD	Dr. Turtz has received intellectual property interests from a discovery or technology relating to health care.
Nitin Tandon	Nitin Tandon has stock in BrainDynamics. The institution of Nitin Tandon has received research support from NIH.
Vanaja konduri, PhD	Dr. konduri has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Diakonos Oncology. Dr. konduri has stock in Diakonos Oncology. The institution of Dr. konduri has received research support from Diakonos Oncology.
Joseph Georges, DO, PhD	Dr. Georges has received intellectual property interests from a discovery or technology relating to health care.
William K. Decker, PhD	Dr. Decker has received personal compensation in the range of $50,000-$99,999 for serving as an officer or member of the Board of Directors for Diakonos Oncology Corp.. Dr. Decker has stock in Diakonos Research, Ltd.. The institution of Dr. Decker has received research support from NIH. The institution of Dr. Decker has received research support from ALSF. The institution of Dr. Decker has received research support from Cancer Cures 4 Kids. Dr. Decker has received intellectual property interests from a discovery or technology relating to health care.

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