Expanded Access to OKN-007 for Patients with Diffuse Midline Glioma, H3 K27-Altered

Study Description:

The purpose of this study is to provide OKN-007 for compassionate use in patients with diffuse midline glioma, H3 K27-altered (DMG), including diffuse intrinsic pontine glioma (DIPG) and collect sufficient information about the patient’s treatment and to provide a complete and accurate case report to health authorities including:

Assessment of OKN-007 safety and tolerability

Assessment of patient’s response.

Study Eligibility:

Inclusion Criteria:

1. Age from > 12 months to < enrollment.

2. Diagnosis of diffuse midline glioma, H3 K27-altered according to the WHO 2021 Classification of Tumors of the Central Nervous System diagnostic criteria including diffuse intrinsic pontine glioma (DIPG). In the absence of a pathologically confirmed diagnosis, a grade IV glioma involving the thalamus, hypothalamus, brainstem, cerebellum, midbrain, or spinal cord, or with a pontine epicenter and diffuse involvement of the pons.

3. Patient has completed definitive radiation therapy as part of standard-of-care treatment or was unable to undergo radiation.

4. Karnofsky performance status > 50 for patients 16 years of age and Lansky performance status > 50 for patients < 16 years of age years of age; patients who are unable to walk because of paralysis, but who are upright in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.

5. Patients must have adequate bone marrow, liver, and renal function:
     • Platelet count > 50,000/μL (transfusion-independent, defined as not receiving platelet transfusions for ≥ 7 days prior to enrollment)
     • Absolute neutrophil count > 1000/μL (after ≥ 7 days without granulocyte colony stimulating factors)
     • Hemoglobin > 8.0 g/dL (no transfusions allowed within 7 days of first OKN-007 treatment [Day 1] to meet entry criteria)
     • Prothrombin/partial thromboplastin time < 1.5 × the upper limit of normal (ULN) for age, international normalized ratio ≤ 1.5
     • Adequate liver function defined as: total bilirubin < 3 × the ULN for age and aspartate aminotransferase and alanine aminotransferase < 2.5 × ULN for age
     • Adequate renal function defined as creatinine clearance (Bedside Schwartz equation) or radioisotope glomerular filtration rate > 70 mL/min/1.73 m2.

6. For females of childbearing potential, negative urinary or serum pregnancy test.

7. Patients must be willing to highly effective contraception for both male and female patients throughout the treatment and for at least 4 months after last treatment administration.

8. Toxicities related to any prior treatments are either stable, stable on supportive therapy, resolved, or in the opinion of the treating physician, clinically non-significant

9. Ability to understand a written informed consent document, and the willingness to sign it. Assent will be obtained when appropriate based on the patient’s age.

Exclusion Criteria:

1. Patient is already participating in or qualifies for and is able to enroll in a clinical trial of OKN-007 and other ongoing clinical trials.
2. Patient has received systemic therapy with an investigational agent within 5 half-lives or 14 days prior to starting OKN-007 treatment, whichever is shorter.
3. Patients completing radiotherapy treatment less than 14 days prior to planned study treatment initiation.
4. Current evidence of uncontrolled, significant intercurrent illness that would, in the treating physician’s judgment, contraindicate the patient’s treatment with OKN-007 due to safety concerns.
5. Patients who, in the opinion of the treating physician, have not fully recovered from recent major surgery to a sufficient extent to tolerate treatment with OKN-007.
6. Known hypersensitivity to OKN-007 or any component in its formulation.
7. Patients taking prohibited medications as described in the current Investigator’s Brochure.
8. Patient is pregnant or actively breastfeeding.