Donor-Derived Anti-CD33 CAR T Cell Therapy (VCAR33) in Patients With Relapsed or Refractory AML After Allogeneic Hematopoietic Cell Transplant

This is a Phase 1/2, multicenter, open-label, first-in-human (FIH) study of donor-derived anti-CD33 Chimeric Antigen Receptor (CAR) T cell therapy (VCAR33) in patients with relapsed or refractory Acute Myeloid Leukemia (AML) after human leukocyte antigen (HLA)-matched allogeneic hematopoietic cell transplant (alloHCT).

Inclusion Criteria:

1. Patients aged ≥18 years

2. Patients must have CD33+ AML in relapse or refractory after alloHCT

3. Patients must be a recipient of an 8/8 (A, B, C, DRB1) HLA-matched related or unrelated donor alloHCT. Patients previously transplanted with VOR33 in the VBP101 study who have R/R AML may also be considered.

4. Disease status at the time of enrollment:

1. Arm A/Morphologic disease: Defined as ≥ 5% blasts (bone marrow) post-HCT

2. Arm B/MRD positive: < 5% blasts (bone marrow) with minimal residual disease of at least 0.1% CD33+ leukemia cells by flow cytometry

5. Performance status: ECOG 0 or 1

6. Patient must have adequate organ function as defined by:

1. Cardiac: Left ventricular ejection fraction (LVEF) ≥ 45% or fractional shortening ≥ 28%

2. Pulmonary: Baseline oxygen saturation > 92% on room air at rest

3. Hepatic: Total bilirubin < 3x institutional upper limit of normal (ULN) (except in case of patients with documented Gilbert's disease < 5x ULN) and aspartate aminotransferase (AST/SGOT)/alanine aminotransferase (ALT/SGPT) < 5x institutional ULN

4. Renal: Serum creatinine must be ≤ 1.2x institutional ULN or creatinine clearance ≥ 60 mL/min for patients with creatinine levels above institutional normal

7. Original alloHCT donor is available and willing to undergo apheresis

Exclusion Criteria:

1. Patients who have undergone more than one alloHCT

2. Patients who have undergone alloHCT with a mismatched unrelated donor, haploidentical donor, or with umbilical cord blood as the stem cell source

3. Patients who will be less than 100 days post-alloHCT at the time of VCAR33 infusion.

4. Patients with any history of Grade III or IV acute GVHD or severe chronic GVHD unless approved by the Sponsor Medical Monitor

5. Patients with evidence of ongoing active acute or chronic GVHD and are taking systemic immunosuppressive agents (> 10 mg daily of prednisone equivalent or other GVHD-directed treatment, including extracorporeal photopheresis). Patients with Grade 1 acute GVHD limited to the skin or mild chronic GVHD limited to the eyes, mouth, or skin controlled with only topical therapy are eligible.

6. Patients with active CNS disease. A lumbar puncture is not required to exclude CNS disease in the absence of clinical signs or symptoms suggesting CNS disease.

7. Patients with the following prior therapy:

1. DLI within 28 days prior to enrollment

2. Prior treatment with any CAR T cell therapy product

8. Patients with active or uncontrolled viral, bacterial, or fungal infection

9. Patients with a history of a human immunodeficiency virus (HIV) infection or acute or chronic active hepatitis B or C infection

10. Patients with a history of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g., cervix, bladder, or breast) unless disease free for at least 3 years after the last definitive therapy

11. Female patients of childbearing potential who are pregnant or breastfeeding

Conditions:
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute