FDA Grants Fast Track Designation to DOC1021 for Glioblastoma

The FDA has granted a fast track designation to the dendritic cell vaccine DOC1021 for use as a potential therapeutic option in patients with glioblastoma multiforme.¹

The designation is based on preliminary safety and efficacy findings from a phase 1 trial (NCT04552886).

DOC1021, which was developed at the Texas Medical Center in Houston, mimics a viral infection with the patient’s cancer markers and harnesses the body’s ability to find and kill infected cells. The vaccine uses a “double-loading” technique that stimulates a novel viral recognition and response pathway. DOC1021 uses patients’ dendritic cells to load unique cancer markers internally and externally into the immune cells, as would occur in a viral infection.

Patients’ individualized DOC1021 treatments are prepared and administered through 3 injections that target the deep cervical lymph node chains. This treatment leads to immune responses that target the central nervous system directly.

“The FDA’s decision acknowledges the potential of this new treatment approach for a very challenging disease,” Mike Wicks, chief executive officer of Diakonos, stated in a news release. “Our protocol represents a first for cancer immunotherapy and could be viable for many types of cancers beyond glioblastoma multiforme.”

“The vaccine's mechanism of action and its unique route of administration showcase the potential of harnessing the body's immune system to combat glioblastoma,” Joseph Georges, DO, PhD, assistant professor of neurosurgery at the University of Arizona College of Medicine — Phoenix, added in the press release.

The single-arm, open-label, first-in-human phase 1 trial is evaluating the safety and feasibility of delivering DOC1021 in 9 to 24 adult patients with glioblastoma who have undergone neurosurgical tumor resection and in whom a neuropathological diagnosis has been established.² Eligible patients include those with potentially resectable glioblastoma who are deemed good candidates for adjuvant chemotherapy and radiation therapy, including those with tumors deemed suitable for gross total resection or partial resection. Patients must have adequate liver, kidney, immune, and bone marrow function and have an ECOG performance status of 2 or lower.

Patients will be excluded if they have locally advanced tumors deemed unresectable and/or recurrent tumors after prior vaccination; used a nonstandard adjuvant treatment regimen of chemoradiation and temozolomide (Temodar); have any uncontrolled or severe condition that could affect study participation, including hyperthyroidism, hypothyroidism, systemic autoimmune disorders, untreated viral hepatitis, or autoimmune hepatitis; need or are expected need for concurrent therapy with corticosteroids during the trial’s vaccination phase; received prior treatment with another investigational drug or intervention beyond the prespecified standard of care for glioblastoma; or have active HIV.

The phase 1 trial planned to treat 3 to 6 patients with a starting dose of 3.5 x 10⁶ of DOC1021. If this dose was associated with unacceptable adverse effects (AEs), no further patients would be enrolled at this dose, and a de-escalation cohort of 3 to 6 patients would receive the vaccine at a dose of 1.75 x 10⁶ cells. If the starting dose was not associated with unacceptable AEs, a dose-escalation cohort of 3 to 6 patients would receive a dose of 7.0 x 10⁶ cells. If no unacceptable AEs were associated with the vaccine at 7.0 x 10⁶ cells, a second dose-escalation cohort of 3 to 6 patients would receive a dose of 1.4 x 10⁷ cells.

The primary end point of this trial is the safety and potential toxicity of DOC1021. Secondary end points include overall survival and progression-free survival.

“Because phase 1 clinical trials are generally not statistically powered to demonstrate efficacy, detection of a statistically significant efficacy signal is very promising,” William Decker, PhD, an associate professor of immunology at Baylor College of Medicine and the inventor of the DOC1021 technology, stated in the press release.¹

The phase 1 trial is ongoing at the MD Anderson Cancer Center at Cooper University Health Care in Camden, New Jersey, and at the University of Texas Health Science Center, and it is expected to complete in 2023.

“Historically, glioblastoma outcomes have been notoriously challenging to improve upon,” Georges said in the press release. “From a clinical and scientific standpoint, the results we are observing with DOC1021 are encouraging.”

References

1. Diakonos Oncology awarded FDA fast track designation for innovative dendritic cell vaccine for glioblastoma. News Release. Diakonos Oncology. October 16, 2023. Accessed October 16, 2023. https://www.biospace.com/article/releases/diakonos-oncology-awarded-fda-fast-track-designation-for-innovative-dendritic-cell-vaccine-for-glioblastoma/
2. Dendritic cell vaccination with standard postoperative chemoradiation for the treatment of adult glioblastoma. ClinicalTrials.gov. Updated June 28, 2023. Accessed October 16, 2023. https://clinicaltrials.gov/study/NCT04552886?term=NCT04552886&rank=1