Clinical Study
Our technology has been validated in research study after research study and we continue to pursue active research to further new formulation development and confirm benefit in disease indices where we can have a positive impact.
NEO212 Tumor Trial
NEO212 is a conjugated therapeutic of NeOnc’s highly purified POH formulation and Temozolomide (TMZ). It was developed to potentially provide a better way to deliver TMZ to the brain than TMZ on its own. In this study, NeOnc will look at NEO212’s ability to target preclinical gliomas an MGMT-positive biomarker.
Background
Through several translation studies, NeOnc has validated the ability of its NEO212 conjugated formulation of POH and TMZ to effectively treat CNS-based cancers such as metastatic brain cancer and Glioblastoma (GBM). Since its acceptance by the FDA in 1991, TMZ has become the gold standard for treating gliomas and is generally a component in glioma patient care. TMZ is an alkylating agent that creates alkyl groups in a cell’s DNA that cause enough disruption to kill the cell. Though TMZ cannot differentiate between healthy and cancerous cells, and since cancer cells grow very rapidly, TMZ has a faster effect on them than on other cells. Traditionally, TMZ is administered in pill form and taken orally. Because of the systemic nature of oral therapeutics, TMZ, to be effective, must be able to travel through the digestive system into the blood and then make its way past the blood-brain barrier (BBB) and to the tumor bed. Dosing to overcome dilution by this type of delivery, exposure of the rest of the patient’s tissue and organs, and the ability to cross the BBB threshold create many challenges to effective treatment without creating deleterious side effects.
NEO212 was developed to potentially overcome these issues by allowing either intranasal delivery of TMZ or creating a higher ability for the drug to permeate across the BBB.
Previous Studies
NeOnc has conducted several previous translational studies to look at the effect of NEO212 compared to TMZ alone. In one study, mass spectrometry and modified high-performance liquid chromatography (HPLC) were used to identify and quantify NEO212 and its metabolites in cultured glioblastoma cells in mouse serum, brain, and excreta after oral gavage. The study suggests that NEO 212 preferentially concentrates in brain tumor tissue over normal brain tissue and compared to TMZ alone, has a higher brain plasma ratio, altogether revealing favorable features to encourage its further development as a brain-targeted therapeutic.
In another study, NEO212 was examined to look at its effectiveness in downregulating the production of the alkylating agent MGMT in cancer-derived cells. The study suggests that NEO 212 inhibited MGMT dependent on the proteasomal pathway, and this inhibition is a significant factor in its toxic effect in non-small cell lung cancer (NSCLC) cells.
Proposed Study
The NEO212 Tumor Trial is an open-label phase 1/2 dose-finding, safety and efficacy study of orally administered NEO212 in patients with astrocytoma IDH-mutant, glioblastoma IDH-wildtype or uncontrolled metastases to the brain in patients with select solid tumors. The study will be conducted in two phases and is anticipated to last five years.
Phase 1 is an open-label 3+3 dose escalation of NEO212 alone that will lead into a Phase 2a safety run-in assessing NEO212 with a normal Standard-Of-Care (SOC) in patients with metastases to the brain leading.
Phase 2 will be a two-part efficacy study, with Phase 2a being a run-in study to Phase 1 with a standard 3+3 design used to confirm the safety of the MTD/RP2D of NEO212 when given in combination with select SOC regimens for patients with uncontrolled metastases to the brain. Up to 12 patients will be enrolled in each combination regimen to confirm safety. One dose below the NEO212 MTD/RP2D Cohort Dose will be administered as a starting dose to establish safety (3+3) before moving to Phase 2b with the MTD/RP2D (3+3). If two DLTs are experienced for patients receiving the MTD/RP2D in combination with SOC, the dose de-escalation cohort will be expanded to determine the MTD for a newly established Phase 2b Treatment Group.
Phase 2b is a dose expansion study to assess the efficacy of NEO212 alone at the MTD/RP2D in patients with Astrocytoma IDH-mutant and Glioblastoma IDH-wildtype as a single Treatment Group. A second Treatment Group to study the MTD/RP2D of NEO212 in combination with select SOC regimens in patients with solid tumors and uncontrolled metastases to the brain established in Phase 2a will be evaluated. Phase 2b will be initiated for patients with Astrocytoma IDH-mutant or Glioblastoma IDH-wildtype alongside Phase 2a. There will be up to 28 patients enrolled in each Phase 2b Treatment Group.