Study of Afuresertib Monotherapy in Japanese Relapsed Multiple Myeloma Patients

Inclusion Criteria:

• Written informed consent is provided.
• Japanese females or males aged 20 years or older (at the time consent is obtained).
• Histologically confirmed diagnosis of relapsed multiple myeloma.
• Performance score of 0 and 1 according to the ECOG scale.
• Relapsed after at least 1 line of systemic therapy. The preparative regimen (with orwithout total body irradiation) and subsequent autologous stem cell rescue used for anautologous stem cell transplant are considered as one line of therapy.
• Able to swallow and retain oral medication.
• Male subjects with a female partner of childbearing potential must have had a priorvasectomy or agree to use adequate contraception from the time of the first dose ofstudy drug until three months after the last dose of study drug.
• A female subject is eligible to participate if she is of: (A) Non-childbearingpotential (i.e. physiologically incapable of becoming pregnant): Pre-menopausalfemales with a documented tubal ligation or hysterectomy; Postmenopausal defined as 12months of spontaneous amenorrhea [if unclear, simultaneous follicle stimulatinghormone >40 milli-international units (MIU)/milliliter (mL) and oestradiol <40picograms (pg)/mL (<140 picomoles [pmol]/L) is required as confirmation]. (B) Femaleson hormone replacement therapy (HRT) and whose menopausal status is in doubt mustdiscontinue HRT to confirm post-menopausal status prior to study enrolment. Followingconfirmation, they can resume HRT during the study without use of a contraceptivemethod. (C) Child-bearing potential, has a negative serum pregnancy test within 7 daysprior to enrolment, and agrees to use adequate contraception from screening until fourweeks after the last dose of study drug. Note: The recommended contraceptive methodsare abstinence of sexual intercourse, use of intrauterine device/system, vasectomy,and use of condom with spermicidal agent. An oral contraceptive drug does not offer areliable contraceptive method as a drug-drug interaction may occur.
• Adequate organ system functions as defined in the protocol
• Subjects with a history of autologous stem cell transplant are eligible provided thefollowing criteria are met: transplant completed >180 days prior to enrolment; noactive infection (e.g. cytomegalovirus, varicella-zoster virus); meets the remainderof the eligibility criteria outlined in this protocol.

Exclusion Criteria:

• Chemotherapy, radiotherapy, immunotherapy or other anti-myeloma therapy within 28 daysprior to enrolment. In addition, any toxicity (except alopecia) should be recovered to <=Grade 1 by National Cancer Institute - Common Terminology Criteria for AdverseEvents (NCI-CTCAE), version 4.0.
• Use of an investigational drug within 30 days or five half-lives, whichever is longer.
• History of an allogenic stem cell transplant. For patients with history of autologousstem cell transplant, inclusion criteria 10 must be met.
• History of PI3K/AKT inhibitors.
• Current use of prohibited medication or subject who requires any of these medicationsduring treatment of afuresertib, as well as subject who cannot meet the protocolspecified meals and dietary restrictions
• Current use of oral corticosteroids, except inhaled or topical use.
• Uncontrolled diabetes mellitus by diet, exercise or medicinal therapies includinginsulin, and with fasting serum glucose >=130 mg/dL (>=7.28 millimoles [mmol]/L).
• Use of anticoagulants other than low dose (prophylactic) anticoagulants for subjectwhose Prothrombin time (PT)/international normalization ratio (INR) and activatedpartial thromboplastin time (APTT) is <=1.5 x upper limit of normal (ULN).
• Presence of active Gastro-intestinal (GI) disease or other condition that could affectGI absorption (e.g. malabsorption syndrome) or predispose subject to GI ulceration.
• Any major surgery that required hospitalization within last four weeks.
• Any serious or unstable pre-existing medical, psychiatric, or other conditions (including lab abnormalities) that could interfere with subject safety or obtaininginformed consent.
• Active infection requiring parenteral or oral anti-infective treatment.
• Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensatedrespiratory, hepatic, renal, or cardiac disease).
• Central nervous system malignancies, primary or metastatic.
• Diagnosis of or treatment history for another malignancy within 2 years, with theexception of complete resection of basal cell carcinoma or squamous cell carcinoma ofthe skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.
• History of known infection with human immunodeficiency virus (HIV).
• Positive hepatitis B surface (HBs) antigen or hepatitis B virus (HBV) Deoxyribonucleicacid (DNA). If negative for HBs antigen and positive for both or either of hepatitis Bcore (HBc) and HBs antibodies, HBV DNA needs to be negative.
• Positive hepatitis C virus (HCV) antibody
• Corrected QT interval (QTc) >450 milliseconds (msec) or QTc > 480 msec for patientswith bundle branch block. The QTc is the QT interval corrected for heart rateaccording to Fridericia's formula (QTcF). Note: The QTc should be based on single oraveraged QTc values of triplicate ECGs obtained over a brief recording period.
• Other clinically significant ECG abnormalities, including 2nd or 3rd degreeatrioventricular block.
• History of myocardial infarction, acute coronary syndromes (including unstableangina), coronary angioplasty or stenting or bypass grafting within the past sixmonths.
• Class III or IV heart failure as defined by the New York Heart Association (NYHA)functional classification system
• Pregnant or lactating female.
• Known hypersensitivity to any components of the study treatment.
• Others who are considered as inappropriate to participate in this study byinvestigators.