A Phase Ib/II Multicenter Open-label Study of Bemcentinib (BGB324) in Patients With AML or MDS

Inclusion Criteria

• Provision of signed written informed consent.
• Histological, molecular or cytological confirmation of:
• Part A: Participants must have received previous treatment with cytotoxic chemotherapy (with or without hematopoietic stem cell transplantation) or a gene expression modulator, such as a demethylating agent. Participants suitable for intensive chemotherapy should be in second or subsequent relapse or be refractory to at least two induction regimens. If eligible they should have undergone hematopoietic stem cell transplantation. Participants receiving an allograft in first remission would be eligible at the time of relapse. Participants who are unsuitable for intensive chemotherapy as a result of advanced age or co-morbidities should have relapsed following at least one line of therapy or be refractory.
• Part B1: Participants with AML who are unsuitable for intensive chemotherapy as a result of advanced age or co-morbidities. Participants should have relapsed following at least one line of therapy or be refractory to such prior therapy. Participants should not have received standard dose intensive chemotherapy.
• Part B2: Participants with AML who are unsuitable for intensive chemotherapy as a result of advancing age or co-morbidities and who are suitable to receive treatment with cytarabine.
• Part B3: Participants with AML who are unsuitable for intensive chemotherapy as a result if advancing age or co-morbidities and who are suitable to receive treatment with decitabine.
• Part B4: Participants with MDS (with the exception of deletion 5q MDS) including intermediate and high-risk participants who must have received prior treatment for their disease. Prior treatment may include those participants who have received hypomethylating agents, decitabine or other approved treatments for MDS.
• Part B5: Participants with relapsed or refractory AML who are unsuitable for intensive chemotherapy as a result of advanced age or co-morbidities meeting the following criteria:
• Must have received at least one prior treatment for AML Are suitable to receive treatment with "low-dose" cytarabine (LDAC). LDAC is defined as 20 mg cytarabine administered subcutaneously twice daily for 10 days every 28 days. The number of participants with refractory AML, defined as no hematological response to last AML treatment and/or participants who have received 2 or more prior treatments for AML, will be restricted to 1/3 of the sample size (i.e. no more than 6 evaluable participants).
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2.
• Age 18 years or older.
• Female participants of childbearing potential must have a negative serum pregnancy test within 3 days prior to taking their first dose of bemcentinib. Male participants and female participants of reproductive potential must practice highly effective methods of contraception (such as hormonal implants, combined oral contraceptives, injectable contraceptives, intrauterine device with hormone spirals, total sexual abstinence, vasectomy) throughout the study and for >=3 months after the last dose of bemcentinib.

Female participants are considered NOT of childbearing potential if they have a history of surgical sterility or evidence of post-menopausal status defined as any of the following:

• Natural menopause with last menses >1 year ago.
• Radiation induced oophorectomy with last menses >1 year ago.
• Chemotherapy induced menopause with last menses >1 year ago.

Exclusion Criteria

• Participants who have a matched donor and are candidates for allogeneic bone marrow transplantation.
• Pregnant or lactating
• History of the following cardiac conditions:
• Congestive cardiac failure of >Class II severity according to the New York Heart Association (defined as symptomatic at less than ordinary levels of activity)
• Ischemic cardiac event including myocardial infarction within 3 months prior to first dose. Participants with prior hist