A Study of Venetoclax in Combination With Cobimetinib and Venetoclax in Combination With Idasanutlin in Patients Aged >/= 60 Years With Relapsed or Refractory Acute Myeloid Leukemia Who Are Not Eligible for Cytotoxic Therapy

Inclusion Criteria:

- Age >/= 60 years

- Histological confirmation of relapsed or refractory AML after prior anti-leukemic
therapy by WHO Classification

- Not eligible for cytotoxic therapies

- Ineligible for allogeneic stem cell transplant

- Life expectancy of at least 12 weeks

- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2

- Adequate liver and renal function

Exclusion Criteria:

- Patients with acute promyelocytic leukemia (French-American-British [FAB] class M3
AML)

- Known active central nervous system (CNS) involvement with AML at study entry

- Prior exposure to Bcl-2 inhibitors, murine double minute 2 (MDM2) antagonists or prior
exposure to experimental treatment targeting Raf, mitogen-activated protein kinase
(MEK), or the mitogen-activated protein kinase (MAPK) RAS/RAF/MEK/ERK MAPK pathway

- Positive for hepatitis C virus (HCV), hepatitis B surface antigen (HBsAg) and known
history of HIV, malignancy, active infection and cardiovascular diseases (CVs)

- Received strong cytochrome (CYP) 3A inhibitors, moderate CYP3A inhibitors, strong
CYP3A inducers and moderate CYP3A inducers within 7 days prior to initiation of study
treatment

- History of symptomatic Clostridium difficile infection within 1 month prior to dosing

Additional phase specific exclusion criteria:

Phase Ib Dose Escalation Arm A (Venetoclax and Cobimetinib)

- History or evidence of retinal pathology on ophthalmologic examination that is
considered a risk factor for neurosensory retinal detachment/central serous
chorioretinopathy (CSCR), retinal vein occlusion (RVO), or neovascular macular
degeneration

- Left ventricular ejection fraction (LVEF) below institutional lower limit of normal
(LLN) or below 50%, whichever is lower

Phase Ib Dose-Escalation Arm B (Venetoclax and Idasanutlin):

Received the following within 7 days prior to the initiation of study treatment:

- Strong CYP2C8 inhibitors or CYP2C8 substrates

- OATP1B1/3 substrates

Received the following within 14 days prior to the initiation of study treatment:

* Strong CYP2C8 inducers

- Received hormonal therapy (apart from luteinizing hormone releasing hormone
agonist/antagonist for prostate cancer and hormone replacement therapy) within 2 weeks
prior to the first dose of study treatment

- History of liver cirrhosis by radiologic, clinical or laboratory data, or biopsy
despite normal liver function tests

Phase II Expansion Arm A and Arm B:

- Received the following within 7 days prior to the initiation of study treatment:

- Strong CYP2C8 inhibitors or CYP2C8 substrates

- OATP1B1/3 substrates

- Received the following within 14 days prior to the initiation of study treatment:

* Strong CYP2C8 inducers

- History or evidence of retinal pathology on ophthalmologic examination that is
considered a risk factor for neurosensory retinal detachment/CSCR, RVO, or neovascular
macular degeneration

- LVEF below institutional LLN or below 50%, whichever is lower

- Received hormonal therapy (apart from luteinizing hormone releasing hormone
agonist/antagonist for prostate cancer and hormone replacement therapy) within 2 weeks
prior to the first dose of study treatment

- History of liver cirrhosis by radiologic, clinical or laboratory data, or biopsy
despite normal liver function tests