Cellipoint Bioservices entered an agreement with Diakonos Oncology in October 2023 for the development and manufacturing of DOC1021, an autologous dendritic cell (DC) vaccine. The collaboration was announced after Diakonos Oncology revealed promising results of the ongoing Phase I trial evaluating DOC1021 in newly diagnosed patients with glioblastoma multiforme (GBM) administered following surgical intervention and standard postoperative chemoradiation. The FDA subsequently granted the vaccine a Fast Track Designation for the indication. Currently, the only FDA-approved DC vaccine, Dendreon’s Provenge, did not make a lasting impact, indicating significant developmental challenges for DOC1021 and other agents using a DC-based platform, according to GlobalData, a leading data and analytics company.

GBM is the most frequent and aggressive primary brain tumor associated with a grim prognosis, underscoring the need for new therapeutic strategies. DC-based tumor vaccines, such as DOC1021, present a potential innovative treatment. DC-based tumor vaccines trigger the patient’s adaptive immunity to elicit a cytotoxic T-lymphocyte response against tumor cells expressing the target antigens, resulting in tumor lysis.

Jasminemay Barcelon, Oncology & Hematology Analyst at GlobalData comments: “Many clinical trial studies involving DC vaccines have reported induction of an antitumoral response and improved survival after DC vaccine administration. Most DC vaccines are in development for the adjuvant setting in conjunction with standard-of-care (SOC) treatments and have gained some success in other indications, such as Dendreon’s Provenge.”

Provenge, a DC-based vaccine for asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer, was granted FDA approval based on an extended median overall survival (OS) of 4.1 months longer than placebo. However, the Phase III trial results garnered criticism, as the control arm performed worse than expected. There has also been limited uptake of Provenge in the clinic due to its associated cost and initial unclear reimbursement status. However, Provenge is undergoing studies in combination with checkpoint inhibitors and radiation therapy.

The current pipeline of dendritic cell vaccines in glioblastoma includes 21 ongoing global clinical trials with five Phase I, four Phase I/II, nine Phase II, one Phase II/III, and two planned Phase III. Despite promising safety and efficacy data, only Northwestern Biotherapeutics’ DCVax-L vaccine has met clinical expectations for approval in Germany for GBM patients, making it difficult to ascertain the future success of Diakonos Oncology’s DOC1021. According to GlobalData, Phase I drugs for GBM have an 82% phase transition success rate (PTSR) indication benchmark, whereas DOC1021 possesses a 55% PTSR, 27% below the indication benchmark.

In terms of direct competitors for DOC1021 in GBM, DCVax-L is a potential contender. DCVax-L employs a similar DC-based vaccine platform, which has an orphan drug designation by the FDA for the adjuvant treatment of GBM and low-grade glioma and has seen a substantially improved OS in a Phase III trial in newly diagnosed patients. Northwestern Biotherapeutics recently announced plans for the submission of a Marketing Authorization Application to the Medicines and Healthcare Products Regulatory Agency for commercial approval of DCVax-L in the UK.

Additionally, AiVita Biomedical’s AVGBM-1 and Immunomic Therapeutics’ ITI-1000 have planned Phase III trials following success in Phase II trials.

Barcelon concludes: “GBM is an indication with a very high unmet need and is likely to see a large impact from cell therapies. DC-based vaccines will be able to penetrate the market effectively in such a difficult-to-treat indication, pending success in clinical trial phase progression and comparative clinical translation against other well-established immuno-oncology therapies.

“The low likelihood of DOC1021 approval for GBM of 1% reflects current limitations in DC-based vaccine development, including improved antigen selection, potential suboptimal clinical trial design and criteria, and difficulties in labor-intensive manufacturing and cost. Considerable challenges await Diakonos Oncology’s DOC1021 journey in the clinical trial space as GlobalData continues to monitor the progress of these trials with interest.”