A Multiple Ascending Dose Study of MEDI7247 in Patients With Selected Relapsed/Refractory Hematological Malignancies

Inclusion criteria

• Confirmed relapsed/refractory diagnosis of select hematologic malignancies for which no standard/salvage therapies are available.
• Age ≥ 18 years at the time of screening.
• Written informed consent and any locally required authorization
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Liver Function Tests: AST and ALT ≤ 3 × ULN, and serum TBL ≤ 1.5 × ULN, unless consistent with Gilbert's syndrome for which TBL ≤ 2.5 × ULN is allowed.

• CrCL ≥ 40 mL/min 6. Female patients of childbearing potential who are sexually active with a nonsterilized male partner must use at least one highly effective method of contraception from 7 days post-screening, and must agree to continue using such precautions for 90 days after the last dose of investigational product.

• Nonsterilized male patients who are sexually active with a female partner of childbearing potential must use a male condom plus spermicide from 7 days post-screening and for 90 days after receipt of the last dose of investigational product.

Exclusion criteria

• Received cytotoxic chemotherapy within 21 days (or 42 days for nitrosureas or mitomycin C) prior to the first scheduled dose of MEDI7247.
• Received major surgery (as defined by the Investigator), radiotherapy, or immunotherapy (including immune checkpoint inhibitors and adoptive cellular therapy such as autologous or donor NK cell or T lymphocyte infusions (e.g. CAR -T cells)) within 28 days of the first scheduled dose of MEDI7247.
• Received an investigational drug within 14 days of the first scheduled dose of MEDI7247 or not recovered from associated toxicities.
• Patients who have previously received an autologous SCT, are excluded if less than 120 days have elapsed from the time of transplant or the patient has not recovered from transplant-associated toxicities prior to the first scheduled dose of MEDI7247.
• History of liver cirrhosis, liver fibrosis or prior liver irradiation regardless of the time interval (not including total body irradiation administered during allogeneic SCT).
• Failure to recover from all prior treatment-related non-hematological toxicities to ≤ Grade 1 prior to the first scheduled dose of MEDI7247 (except for alopecia and neuropathy).
• Patients at risk of non-disease related major bleeding (eg, recent GI hemorrhage or neurosurgery, within previous 21 days).
• Current severe active systemic disease including active concurrent malignancy
• Central nervous system (CNS) disease that is untreated, symptomatic, or requires therapy to control symptoms.
• Active human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infections at the time of screening.