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Inclusion Criteria:

* Histological confirmation of relapsed or refractory AML after prior anti-leukemic therapy by WHO classification
* Ineligible for cytotoxic therapy defined by the following:

  a. Age (\>/=) 75 years or b. age 18- 74 years with at least one of the following comorbidities: i. Eastern Cooperative Oncology Group (ECOG) Performance Status of 2 or 3 ii. Cardiac history of congestive heart failure requiring treatment or ejection fraction (\</=) 50% or chronic stable angina iii. Diffusing capacity of the lungs for carbon monoxide (\</=) 65% or forced expiratory volume in the first second of expiration (\</=) 65% iv. Creatinine clearance (\>/=) 30 mL/min to\< 45 mL/min v. any other comorbidity that the physician judges to be incompatible with intensive chemotherapy must be reviewed and approved by the Medical Monitor before screening and study enrollment.
* 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
* ECOG Performance Status (\>/=) 3 in patients who are (\>/=) 75 years old or ECOG Performance Status of 4, regardless of age
* 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 arm specific exclusion criteria:

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

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
* History of liver cirrhosis by radiologic, clinical or laboratory data, or biopsy despite normal liver function tests
* Received treatment with oral or parenteral anticoagulants/anti-platelet agents within 7 days prior to initiation of study treatment.

• Los Angeles, California, United States
• Sacramento, California, United States
• San Francisco, California, United States
• Aurora, Colorado, United States
• Boston, Massachusetts, United States
• New York, New York, United States
• Winston-Salem, North Carolina, United States
• Houston, Texas, United States
• Edmonton, Alberta, Canada
• Toronto, Ontario, Canada
• Montreal, Quebec, Canada
• Bobigny, France
• Marseille, France
• Pessac, France
• Bologna, Emilia-Romagna, Italy
• Pesaro, Emilia-Romagna, Italy
• Roma, Emilia-Romagna, Italy