A Phase 1 Study of Orca-Q in Recipients Undergoing Allogeneic Transplantation for Hematologic Malignancies

Key Inclusion Criteria:

• Age at the time of enrollment:

• For MAC with fully matched donor (Arm A with 8/8 donor and Arm C) and NMA/RIC: Age ≥ 12 and ≤ 78 years
• For MAC with mismatched donors (Arm A with 7/8 donor and Arm B): Age ≥ 12 and ≤ 65 years
• Diagnosed acute myeloid, lymphoblastic or mixed phenotype leukemia, or high or very high risk myelodysplastic syndrome (MDS) either in complete remission (CR) or with ≤ 10 percent of blast cells in bone marrow (BM)
• Indicated for allogeneic hematopoietic stem cell transplant (alloHCT)
• Matched to a 8/8 or 7/8 related or unrelated donor, or to a related haploidentical donor
• Estimated glomerular filtration rate (eGFR) > 50 mL/minute (MAC with tacrolimus) or > 30 mL/minute (NMA/RIC or MAC without tacrolimus)
• Cardiac parameters: Cardiac ejection fraction ≥ 45 percent (MAC) or ≥ 40 percent (NMA/RIC)
• Diffusing capacity of the lung for carbon monoxide (DLCO) (adjusted for hemoglobin) ≥ 50 percent for MAC or ≥ 40 percent for NMA/RIC
• Liver function: Total bilirubin < 1.5 times upper limit of normal (ULN) (MAC) or < 3 times ULN (NMA/RIC); alanine transaminase (ALT)/aspartate transaminase (AST) < 3 times ULN (MAC) or < 5 times ULN (NMA/RIC)
• Participants enrolling on NMA/RIC-alloHCT arms must be deemed unfit for a myeloablative alloHCT per assessment of the principal investigator (PI)

Key Exclusion Criteria:

• Prior alloHCT
• Currently receiving corticosteroids or other immunosuppressive therapy except for approved disease-specific therapy for the patient's underlying hematologic malignancy. Topical corticosteroids or oral systemic corticosteroid doses less than or equal to 10 mg/day are allowed
• Planned donor lymphocyte infusion (DLI)
• Planned pharmaceutical in vivo or ex vivo T cell depletion, e.g., post-transplant cyclophosphamide (Cy) or alemtuzumab
• Positive anti-donor HLA antibodies against a mismatched allele in the selected donor
• Low performance score: For MAC: Karnofsky Performance Score (KPS) < 70 percent, For NMA/RIC: <60 percent
• High HCT-specific Comorbidity Index (HCT-CI): For MAC > 4, For NMA/RIC >6
• Uncontrolled bacterial, viral or fungal infections (currently taking antimicrobial therapy and with progression or no clinical improvement) at time of enrollment
• Seropositive for human immunodeficiency virus (HIV)-1 or -2, human T-lymphotropic virus (HTLV)-1 or -2 or Hepatitis B surface antigen (HbsAg) or anti-Hepatitis C virus (HCV) antibody (Ab)
• Any uncontrolled autoimmune disease requiring active immunosuppressive treatment
• Concurrent malignancies or active disease within 1 year, except non-melanoma skin cancers that have been curatively resected. Patients with concurrent indolent hematologic malignancies that do not require active treatment and are under active surveillance only (such as CLL, low-grade lymphomas, smoldering MM, MZL) may be included with the approval of Medical Monitor
• History of idiopathic or secondary myelofibrosis
• Women who are pregnant or breastfeeding