A Study Conducted in Subjects With Relapsed/Refractory Multiple Myeloma (MM); to Determine Dose of Afuresertib in Combination With Carfilzomib (Part 1) and to Investigate the Safety, Pharmacokinetic and Clinical Activity of the Combination Compared With Carfilzomib Alone (Part 2)

Inclusion Criteria:

- Provided signed written informed consent, which includes compliance with the
requirements and restrictions listed in the consent form

- Histologically confirmed diagnosis of MM

- Received at least two prior therapies including bortezomib and an immunomodulatory
agent and demonstrated disease progression on or within 60 days of completion of the
last therapy. Subjects in Part 2 must also have measurable disease defined as having
at least one of the following: Serum M-protein >=0.5 gram/ deciliter (g/dL) (>=5
gram/Liter [g/L]), Urine M-protein >=200 mg/24 hour (h), Serum free light chain (FLC)
assay: Involved FLC level >=10 mg/dL (>=100 mg/L) and an abnormal serum free light
chain ratio (<0.26 or >1.65), Biopsy proven plasmacytoma (should be measured within
28 days of the Screening Visit)

- Male or female, 18 years or older

- Performance status score of 0 - 1 according to the Eastern Cooperative Oncology Group
(ECOG) scale

- Able to swallow and retain orally administered study treatment and does not have any
clinically significant Gastro-intestinal (GI) abnormalities that may alter absorption
such as malabsorption syndrome or major resection of the stomach and/or bowels or
predispose subject to GI ulceration

- For the Alternate Arm (100 mg) only (if opened), willingness to undergo paired
pre-dose and post-dose bone marrow aspirate and biopsies

- Fasting serum glucose <126 mg/dL (<7 millimole/liter [mmol/L]). Subjects diagnosed
previously with Type 2 diabetes must also meet the additional following criteria:
Controlled diabetes for >=6 months prior to enrolment, Hemoglobin A1c (HbA1c) =<8% at
Screening visit

- Adequate organ system function defined as: Hematologic: Absolute neutrophil count
(ANC) >=1.0 X 10/meter (m)^9/L, Hemoglobin >=8.0 g/dL, Platelets >=50 X 10 m^9/L,
Prothrombin time/ International normalization ratio (PT/INR) <=1.5; Hepatic: Total
bilirubin =<1.5 X Upper limit of normal (ULN) (isolated bilirubin >1.5 X ULN is
acceptable if bilirubin is fractionated and direct bilirubin <35%), Aspartate
aminotransferase (AST) and Alanine aminotransferase (ALT) =<1.5 X ULN, Serum Calcium
corrected for albumin: =<12 mg/mL (=3 mmol/L); Cardiac: Corrected QT interval
duration (QTc) interval <470 milliseconds (msecs), Left Ventricular Ejection Fraction
(LVEF) (Echocardiogram [ECHO] or Multigated acquisition scan [MUGA]) >=50%, Renal:
Serum Creatinine <2.5 mg/dL, Estimated glomerular filtration rate (GFR) or 24-hr
urine creatinine clearance >=30 mL/ minute [min] (Estimated glomerular filtration
rate will be calculated by the Modification of Diet in Renal Disease [MDRD] equation.
When both a calculated and 24-hr creatinine clearance are available, the 24-hr value
will be used). Note: Laboratory results obtained during Screening should be used to
determine eligibility criteria. In situations where laboratory results are outside
the permitted range, the investigator may opt to retest the subject and the
subsequent within range screening result may be used to confirm eligibility

- A female subject is eligible to participate if she is of Non-childbearing potential.
Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt
will be required to use one of the contraception methods as explained by the
Investigator/designee, if they wish to continue their HRT during the study.
Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status
prior to study enrollment. For most forms of HRT, at least 2 4 weeks will elapse
between the cessation of therapy and the blood draw; this interval depends on the
type and dosage of HRT. Following confirmation of their post-menopausal status, they
can resume use of HRT during the study without use of a contraceptive method.
Child-bearing potential, has a negative serum pregnancy test within 7 days prior to
start of study drugs, during the screening period, and agrees to use one of the
contraception methods explained by the Investigator/designee from screening until
four weeks after the last dose of afuresertib or carfilzomib

- Male subjects with female partners of child-bearing potential must have had a prior
vasectomy or agree to use one of the contraception explained by the
Investigator/designee. This criterion must be followed from the time of the first
dose of study drugs until 10 days after the last dose of afuresertib or carfilzomib

Exclusion Criteria: Subjects meeting any of the following criteria must not be enrolled in
the study:

- Prior treatment with carfilzomib and/or participation in any Phase 3 carfilzomib
trial

- Chemotherapy, radiotherapy, immunotherapy, or other anti-myeloma therapy within 14
days prior to the first dose of any one of the drugs in the combination regimen. In
addition, any drug-related toxicity should have recovered to Grade 1 or less

- Use of an investigational drug within 14 days or five half-lives, whichever is
shorter, preceding the first dose of any one of the drugs in the combination regimen

- History of an allogeneic stem cell transplant

- Current use of prohibited medication during treatment with afuresertib

- Current chronic use of oral corticosteroids, with the exception of inhaled or topical
steroids

- Unwillingness to follow the lifestyle and dietary restrictions

- Evidence of mucosal or internal bleeding

- Unresolved toxicity >=Grade 1 National Cancer Institute Common Terminology Criteria
for Adverse Events, version 4 (NCI-CTCAE, 2009) from previous anti-cancer therapy
except alopecia and <=Grade 2 peripheral neuropathy

- Any major surgery within the last four weeks

- Type 1 diabetes mellitus

- Any serious or unstable pre-existing medical, psychiatric disorder, or other
condition (including lab abnormalities) that could interfere with subject's safety,
obtaining informed consent or compliance to the study procedures

- Impaired cardiac function or clinically significant cardiac diseases, including any
one of the following: Class II, III, or IV heart failure as defined by the New York
Heart Association functional classification system; uncontrolled angina; clinically
significant pericardial disease; severe uncontrolled ventricular arrhythmias, sick
sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3
conduction system abnormalities unless subject has a pacemaker. Prior to study entry,
any ECG abnormality at Screening has to be documented by the investigator as not
medically relevant. Other clinically significant ECG abnormalities including second
degree (Type II) or 3rd degree atrioventricular (AV) block; history of myocardial
infarction, acute coronary syndromes (including unstable angina), coronary
angioplasty, or stenting or bypass grafting within six months of Screening; pulmonary
hypertension

- Known active infection requiring parenteral or oral anti-biotic treatment

- Previous or concurrent malignancies are allowed if it is clear that the other tumor
is not contributing to the subject's illness. The subject must not be receiving
active therapy, other than hormonal therapy, for this disease and the disease must be
considered medically stable for at least 2 years.

- Pregnant or lactating female

- Known Human Immunodeficiency Virus (HIV) infection

- Subjects who are Hepatitis B surface antigen (HbSAg) positive. Subjects with a
positive test for Hepatitis C (HCV) antibody are excluded, regardless of viral load.
If hepatitis C antibody is positive, a confirmatory recombinant immunoblot assay
(RIBA) test may be performed. If the RIBA test is negative, the subject is eligible
for the study