A Study of ASP2215 (Gilteritinib) Combined With Atezolizumab in Patients With Relapsed or Treatment Refractory FMS-like Tyrosine Kinase (FLT3) Mutated Acute Myeloid Leukemia (AML)

Inclusion Criteria

• Subject is considered an adult according to local regulation at the time of signing informed consent form (ICF).
• Subject has defined AML by the World Health Organization (WHO) criteria (2017) and fulfills one of the following:
• Refractory to at least 1 cycle of induction chemotherapy
• Relapsed after achieving remission with a prior therapy
• Subject is positive for FLT3 mutation in bone marrow or blood after completion of the subject's last interventional treatment.
• Subject has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 at screening.
• Subject must meet the following criteria as indicated on the clinical laboratory tests:
• Serum Aspartate aminotransferase (AST) and Alanine Aminotransferease (ALT) ≤ 2.5 x upper limit of normal (ULN)
• Serum total bilirubin (TBL) ≤ 1.5 x ULN
• Serum creatinine ≤ 1.5 x ULN or an estimated glomerular filtration rate of > 50 mL/min as calculated by the Modification of Diet in Renal Disease equation.
• Subject is suitable for oral administration of study drug.
• A female subject is eligible to participate if she is not pregnant and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) OR
• WOCBP who agrees to follow the contraceptive guidance throughout the treatment period and for at least 180 days after the final study drug administration.
• Female subject must agree not to breastfeed starting at screening and throughout the study period, and for at least 180 days after the final study drug administration.
• Female subject must not donate ova starting at screening and throughout the study period, and for at least 180 days after the final study drug administration.
• A male subject must not donate sperm starting at screening and throughout the treatment period, and for at least 120 days after the final study drug administration.
• A male subject with female partner(s) of child-bearing potential must agree to use contraception during the treatment period, and for at least 120 days after the final study drug administration.
• Male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or time partner is breastfeeding throughout the treatment period, and for 120 days after the final study drug administration.
• Subject agrees not to participate in another investigational study while on treatment.

Exclusion Criteria

• Subject was diagnosed as acute promyelocytic leukemia.
• Subject has BCR-ABL-positive leukemia (chronic myelogenous leukemia in blast crisis).
• Subject has AML secondary to prior chemotherapy for other neoplasms (except for myelodysplastic syndrome).
• Subject has clinically active central nervous system leukemia.
• Subject has uncontrolled or significant cardiovascular disease, including:
• A myocardial infarction within 12 months
• Uncontrolled angina within 6 months
• History of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, torsades de pointes) or any history of arrhythmia
• Uncontrolled hypertension
• Subject has baseline left ventricular ejection fraction that is ≥ 45%.
• Subject has mean triplicate Fridericia-corrected QT interval (QTcF) > 450 ms at Screening based on central reading.
• Subject has congenital or acquired Long QT Syndrome at screening.
• Subject has hypokalemia and/or hypomagnesemia at screening.
• Subject has been diagnosed with another malignancy that requires concurrent treatment or hepatic malignancy regardless of the need for treatment.
• Subject has clinically significant coagulation abnormality unless secondary to AML.
• Subject is receiving or plans to receive concomitant chemotherapy or immunotherapy.
• Subject has had major surgery within 4 weeks prior to the first study dose.
• Subject has radiation therapy within 4 weeks prior to the first study dose.
• Subject requires treatment with concomitant drugs that are strong inducers of Cytochrome P450 (CYP3A).
• Subject has known pulmonary disease with diffusion capacity of lung for carbon monoxide ≤ 65%, forced expiratory volume in the first second (FEV1) ≤ 65%, dyspnea at rest or requiring oxygen or any pleural neoplasm.
• Subject with systemic fungal, bacterial, viral or other uncontrolled infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment. Subject needs to be off pressors and have negative blood cultures for 48 hours.
• Subject has not recovered from any prior therapy related toxicities.
• Subject is known to have human immunodeficiency virus infection.
• Subject has active hepatitis B or C or other active hepatic disorder.
• Subject has previously been treated with gilteritinib, quizartinib or crenolanib (will only apply to subjects enrolled in the phase 2 portion of the study).
• Subject has active clinically significant graft-versus-host disease (GVHD) or is on treatment with systemic corticosteroids for GVHD.
• Subject has relapsed after allogeneic hematopoietic stem cell transplant (HCST).
• Subject has an active autoimmune disorder that makes the subject unsuitable for study treatment or participation.
• Subject has any condition that makes the subject unsuitable for study participation.