GD2 CAR T Cells in Diffuse Intrinsic Pontine Gliomas (DIPG) & Spinal Diffuse Midline Glioma(DMG)

INCLUSION CRITERIA

1. Disease Status: Diagnosis of H3K27M mutant diffuse midline glioma (DMG)

2. H3K27M or H3K27I mutation. Confirmed by CLIA test.

3. Age: Greater than or equal to 2 year of age and less than or equal to 60 years ofage.

4. Prior Therapy:

• At least 4 weeks following completion of standard upfront radiation therapy.

• At least 3 weeks post chemotherapy or 5 half-lives, whichever is shorter, musthave elapsed since any prior systemic therapy, except for systemicinhibitory/stimulatory immune checkpoint therapy that requires 3 months.

• Dordaviprone (Modeyso), previously known as ONC201, may be taken as priortherapy but - just as with other anti-cancer medications - administration mustcease at least 5 half-lives prior to enrollment

5. Performance Status: Subjects > 16 years of age: Karnofsky ≥ 60% OR Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; Subjects ≤ 16 years of age: Lansky scale ≥ 60%. Subjects who are unable to walk because of paralysis, but who are up in awheelchair, will be considered ambulatory for the purpose of assessing theperformance score.

6. Normal Organ and Marrow Function (supportive care is allowed per institutionalstandards, i.e. filgrastim, transfusion) i. ANC ≥ 1000/uL ii. Platelet count ≥ 100,000/uL iii. Absolute lymphocyte count ≥ 150/uL iv. Hemoglobin ≥ 8 g/dL v.Adequate renal, hepatic, pulmonary and cardiac function defined as:

• Creatinine within institutional norms for age (i.e.

≤ 2 mg/dL in adults or according to table below in children <18 years) OR creatinineclearance (as estimated by Cockcroft Gault Equation) ≥ 60 mL/min Serum ALT/AST ≤ 3.0 ULN (grade 1)

• Total bilirubin ≤ 1.5 mg/dl, except in subjects with Gilbert's syndrome.

• Cardiac ejection fraction ≥ 45%, no evidence of physiologically significantpericardial effusion as determined by an ECHO, and no clinically significantECG findings

• Baseline oxygen saturation > 92% on room air

7. Pregnancy Test Females of childbearing potential must have a negative serum or urinepregnancy test (females who have undergone surgical sterilization are not consideredto be of childbearing potential) or NA

8. Contraception Subjects of child-bearing or child-fathering potential must be willingto practice birth control from the time of enrollment on this study and for four (4)months after receiving the preparative regimen or for as long as GD2CART cells aredetectable in peripheral blood or CSF.

9. Ability to give informed consent. All subjects ≥ 18 years of age must be able togive informed consent. For subjects <18 years old their legal authorizedrepresentative (LAR) (i.e. parent or guardian) must give informed consent. Pediatricsubjects will be included in age appropriate discussion and written assent will beobtained for those > 7 years of age, when appropriate. If a minor becomes of ageduring participation of this study, he/she will be asked to reconsent as an adult.

EXCLUSION CRITERIA:

1. For Dose Escalation: Bulky tumor involvement of cerebellar vermis or hemispheres (pontocerebellar peduncles involvement is acceptable), or thalamic lesions that inthe investigator's assessment place the subject at unacceptable risk for herniation. For Dose Expansion: Bulky disease that in the investigator's assessment place thesubject at unacceptable risk for herniation. Thalamic DMG is permitted.

2. Clinically significant swallowing dysfunction/dysphagia or prominent medullarydysfunction, as determined by the clinical investigator; or primary cervical cordtumors above C6/7 that represent a high risk of respiratory compromise, asdetermined by the clinical investigator.

3. Current systemic corticosteroid therapy above physiologic replacement levels.

4. Ongoing use of dietary supplements, alternative therapies or extreme dietmodifications or any medication not approved by the investigators

5. Prior CAR therapy.

6. Prior immunomodulatory therapy, except for checkpoint inhibitor therapy after atleast 3 month wash-out.

7. Uncontrolled fungal, bacterial, viral, or other infection. Previously diagnosedinfection for which the patient continues to receive antimicrobial therapy ispermitted if responding to treatment and clinically stable.

8. Diagnosed ongoing infection with:

• HIV,

• Hepatitis B (HBsAg positive) or

• Hepatitis C virus (anti-HCV positive). A history of hepatitis B or hepatitis Cis permitted if the viral load is undetectable per quantitative PCR and/ornucleic acid testing.

9. Clinically significant systemic illness or medical condition (e.g. significantcardiac, pulmonary, hepatic or other organ dysfunction), that in the judgement ofthe principal investigator is likely to interfere with assessment of safety orefficacy of the investigational regimen and its requirements.

10. Women who are pregnant or breastfeeding.

11. In the investigator's judgment, the subject is unlikely to complete allprotocol-required study visits or procedures, including follow-up visits, or complywith the study requirements for participation.

12. Known sensitivity or allergy to any agents/reagents used in this study.

13. Primary immunodeficiency or history of autoimmune disease (e.g. Crohns, rheumatoidarthritis, systemic lupus) requiring systemic immunosuppression/systemic diseasemodifying agents within the last 2 years

• All subject files must include supporting documentation to confirm subjecteligibility.

The method of confirmation can include, but is not limited to, laboratory test results, radiology test results, subject self-report, and medical record review.

*Anyone under 26, please contact Ashley Jacobs and anyone 26 and older, please contact Monica Reddy