Early Studies Investigate Novel IO Strategy in Merkel Cell Carcinoma and Glioblastoma

Treatment with multiple nucleic acid immunotherapy agents is being evaluated in phase 1/2 clinical trials, according to a recent announcement by Immunomic Therapeutics, Inc, developer of ITI-300 and ITI-1000.

Most recently, the first phase 1 clinical study evaluating ITI-3000 was launched to assess treatment in patients with Merkel cell carcinoma (MCC).

ITI-3000 uses the investigational Universal Intracellular Targeted Expression (UNITE) platform, which is powered by lysosome-associated membrane protein, which has created a variety of applications in various therapeutic areas, including infectious diseases, oncology, allergy, and autoimmune diseases.

The first-in-human, open-label trial will be carried out at the University of Washington School of Medicine and the Fred Hutchinson Cancer Center in Seattle, Washington. The trial aims to evaluate the safety, tolerability, and immunogenicity of 4 mg of ITI-3000 in patients with MCC who had previously undergone surgery. Some primary end points include dose-limiting toxicities, adverse events, standard clinical assessments, and safety laboratory parameters.

"This phase 1 clinical trial of ITI-3000 in MCC is an important milestone, as it expands the reach of our immuno-oncology program beyond our ongoing phase 2 study of ITI-1000 (Umitrelimorgene autodencel) in glioblastoma multiforme, to a second potential indication," said William Hearl, PhD, chief executive officer of Immunomic Therapeutics, Inc, in the press release.

In the ongoing phase 2 ATTAC-II study of ITI-1000, a dendritic cell (DC) vaccine, in patients with glioblastoma (GBM; NCT00639639), investigators are trying to determine whether or not pp65 DCs are effective for GBM treatment when given with stronger doses of routine chemotherapy.2

The randomized trial consists of 175 patients aged 18 years and older with newly-diagnosed de novo GBM who have undergone definitive surgical resection of tumor.

The primary outcome is feasibility and safety of vaccination with cytomegalovirus pp65-LAMP mRNA-loaded DCs with or without autologous lymphocyte transfer. Some secondary outcomes include humoral and cellular immune responses and the time to progression from the time of surgery/diagnosis to the date of progression.

A vaccine called pp65 DC has been created with the hopes of teaching immune cells to target a type of immune marker in GBM, the pp65 antigen, by working as a type of immunotherapy. The vaccine will be given as a shot under the skin at day 22-24 after the first temozolomide (Temodar) cycle then at 2-week intervals. Doses 4-10 will be given on day 22-24 of each temozolomide cycle continuing until a total of 10 or until progression or unacceptable toxicity.

Researchers are hopeful that by following this dosing schedule, the immune system will be activated to attack tumor cells in the brain and normal cells will be left alone.

Patients with GBM will be assigned to different treatment groups. Two groups of subjects will receive the pp65 DC vaccine and one group will receive a placebo.

Like ITI-1000, ITI-3000 uses the investigational Universal Intracellular Targeted Expression (UNITE) platform of the company, powered by lysosome-associated membrane protein, which has created a variety of applications in various therapeutic areas, including infectious diseases, oncology, allergy, and autoimmune diseases. According to data from in vivo models, using the lysosomal targeting technology resulted in improved antigen presentation, a balanced immune response, as well as ITI-3000 found to activate antigen-specific CD4-positive T cells.

The plasmid DNA vaccine will be administered through a needle-free injection system which precisely targets delivery to the intramuscular tissue layer.

"Based on the strength of our UNITE platform and strong pre-clinical data generated, to date, we believe ITI-3000 has the potential to address the urgent unmet medical need for therapies to treat this aggressive form of skin cancer."

^REFERENCES:

^{Immunomic Therapeutics Announces Clinical Trial of ITI-3000 for the Treatment of Merkel Cell Carcinoma. News Release. Immunomic Therapeutics, Inc.; February 07, 2022. Accessed February 08, 2022. https://bit.ly/3oAsCSL}

^{Vaccine therapy in treating patients with newly diagnosed glioblastoma multiforme (ATTAC). Clinicaltrials.gov. Accessed February 11, 2022. https://bit.ly/34PYjAc}