A Combination Therapy Study of MK-2206 and AZD6244 in Participants With Advanced Solid Tumors (MK-2206-010)

An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of study drug, whether or not considered related to the use of the product. Any worsening of a pre-existing condition which was temporally associated with the use of study drug was also an AE. The number of participants who discontinued study treatment due to an AE is presented.

Time frame: Up to approximately 20 months

Population: The population consisted of all participants who received at least one dose of study treatment.

An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of study drug, whether or not considered related to the use of the product. Any worsening of a pre-existing condition which was temporally associated with the use of study drug was also an AE. The number of participants who experienced at least one AE is presented.

Time frame: Up to approximately 23 months

Population: The population consisted of all participants who received at least one dose of study treatment.

Adverse events (AEs) were graded using Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. DLTs included: Grade 4 neutropenia lasting for ≥7 days; Grade 3 or Grade 4 neutropenia with fever \>38.5ºC and/or infection requiring antibiotic or anti-fungal treatment; Grade 4 thrombocytopenia (≤25.0 x 10\^9/L); Grade ≥3 non-hematologic toxicity with exceptions; Any drug-related AE, regardless of CTCAE Grade, leading to a dose modification of MK-2206 or AZD6244; Unresolved CTCAE Grade ≥3 drug-related toxicity requiring drug interruption for \>14 days; ≥ Grade 3 signs or symptoms of glucose intolerance and accompanied by ≥ Grade 2 hyperglycemia (glucose \>160 dL or 8.9 mmol/L); ≥ Grade 3 electrolyte abnormalities due to glucose intolerance and not attributable to another cause; Diagnosis of lactoacidosis or ketoacidosis; Persistent increases in corrected QT (QTc) interval (\>60 msec from baseline and/or \>500 msec); Clinically significant bradycardia.

Time frame: Cycle 1 (Up to 28 days)

Population: The population consisted of all participants who completed ≥ 80% of the first cycle of combination therapy unless interruption of study medication was due to toxicity (e.g. DLT).

Radiological evaluation (via computed tomography \[CT\] or magnetic resonance imaging \[MRI\]) of tumor response was assessed every 8 weeks post-treatment during Cycles 1-6, and per institutional standard of care in Cycle 7 and beyond. The best overall tumor response was the best response based on RECIST 1.1 recorded from the start of the study treatment until the end of treatment. Response categories included: Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions; Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions; and Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Participants whose tumor was not evaluable (NE) were missing a valid RECIST1.1 measurement at baseline. The best overall tumor response for participants is presented.

Time frame: Baseline and after every 8 weeks of treatment until documentation of objective response or disease progression (Up to 2 years)

Population: The analysis population consisted of all participants with assessable disease at baseline or measureable disease at baseline per RECIST1.1.