A Phase I Study of MK-2206 in Combination With Standard Chemotherapy in Participants With Locally Advanced or Metastatic Solid Tumors (MK-2206-003)

• ClinicalTrials.gov Identifier: NCT00848718
• Recruitment Status: Completed
• First Posted: February 20, 2009
• Results First Posted: November 12, 2019
• Last Update Posted: November 12, 2019
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Locally Advanced, Metastatic Solid Tumors
• Interventions: Drug: MK-2206; Drug: docetaxel; Drug: erlotinib; Drug: carboplatin; Drug: paclitaxel; Drug: corticosteroid
• Enrollment: 77

Participant Flow

Recruitment Details	77 participants were allocated to one of 3 treatment combinations with MK-2206 according to clinical presentation but 5 participants were not treated due to disease progression before initiation of treatment.
Pre-assignment Details

Arm/Group Title	MK-2206 45 mg QOD+Carboplatin+Paclitaxel	MK-2206 60 mg QOD+Carboplatin+Paclitaxel	MK-2206 90 mg Q3W+Carboplatin+Paclitaxel	MK-2206 135 mg Q3W+Carboplatin+Paclitaxel	MK-2206 200 mg Q3W+Carboplatin+Paclitaxel	MK-2206 45 mg QOD+Docetaxel 75 mg/m^2	MK-2206 90 mg Q3W+Docetaxel 60 mg/m^2	MK-2206 135 mg Q3W+Docetaxel 60 mg/m^2	MK-2206 200 mg Q3W+Docetaxel 60 mg/m^2	MK-2206 45 mg QOD+Erlotinib 100 mg	MK-2206 45 mg QOD+Erlotinib 150 mg	MK-2206 135 mg QW+Erlotinib 100 mg	MK-2206 135 mg QW+Erlotinib 150 mg
Arm/Group Description	Participants received MK-2206 45 mg administered PO on Days 1, 3, 5, and 7 in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.	Participants received MK-2206 60 mg administered PO on Days 1, 3, 5, and 7 in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.	Participants received MK-2206 90 mg administered PO in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.	Participants received MK-2206 135 mg administered PO in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.	Participants received MK-2206 200 mg administered PO in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.	Participants received MK-2206 45 mg administered PO on Days 1, 3, 5, and 7 in combination with Docetaxel 75 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily.	Participants received MK-2206 90 mg administered PO on Day 1 in combination with Docetaxel 60 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily.	Participants received MK-2206 135 mg administered PO on Day 1 in combination with Docetaxel 60 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily.	Participants received MK-2206 200 mg administered PO on Day 1 in combination with Docetaxel 60 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily.	Participants received MK-2206 45 mg administered PO every other day (Days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19 and 21) in combination with Erlotinib 100 mg administered PO once every day of each 21-day cycle.	Participants received MK-2206 45 mg administered PO every other day (Days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19 and 21) in combination with Erlotinib 150 mg administered PO once every day of each 21-day cycle.	Participants received MK-2206 135 mg administered PO on Days 1, 8 and 15 in combination with Erlotinib 100 mg administered PO once every day of each 21-day cycle.	Participants received MK-2206 135 mg administered PO on Days 1, 8 and 15 in combination with Erlotinib 150 mg administered PO once every day of each 21-day cycle.
Period Title: Overall Study
Started	7	9	6	5	6	5	3	5	4	9	4	6	8
Treated	6 [1]	9	5 [1]	5	6	5	3	4 [1]	4	9	4	6	6 [2]
Completed	0	0	0	0	0	0	0	0	0	0	0	0	0
Not Completed	7	9	6	5	6	5	3	5	4	9	4	6	8
Reason Not Completed
Adverse Event	2	2	1	1	1	0	0	1	1	0	0	0	2
Lack of Efficacy	0	0	1	0	0	0	1	0	0	0	0	0	0
Physician Decision	0	1	0	0	1	1	0	0	1	2	0	0	1
Progressive disease before treatment	1	5	1	3	4	4	2	1	2	7	3	6	2
Protocol Violation	0	1	0	0	0	0	0	1	0	0	0	0	1
Withdrawal by Subject	1	0	0	1	0	0	0	0	0	0	1	0	0
Progressive disease during treatment	3	0	3	0	0	0	0	2	0	0	0	0	2
[1] 1 participant was allocated but did not receive treatment due to progression of disease; [2] 2 participants were allocated but did not receive treatment due to progression of disease

Baseline Characteristics

Arm/Group Title		MK-2206 45 mg QOD+Carboplatin+Paclitaxel	MK-2206 60 mg QOD+Carboplatin+Paclitaxel	MK-2206 90 mg Q3W+Carboplatin+Paclitaxel	MK-2206 135 mg Q3W+Carboplatin+Paclitaxel	MK-2206 200 mg Q3W+Carboplatin+Paclitaxel	MK-2206 45 mg QOD+Docetaxel 75 mg/m^2	MK-2206 90 mg Q3W+Docetaxel 60 mg/m^2	MK-2206 135 mg Q3W+Docetaxel 60 mg/m^2	MK-2206 200 mg Q3W+Docetaxel 60 mg/m^2	MK-2206 45 mg QOD+Erlotinib 100 mg	MK-2206 45 mg QOD+Erlotinib 150 mg	MK-2206 135 mg QW+Erlotinib 100 mg	MK-2206 135 mg QW+Erlotinib 150 mg	Total
Arm/Group Description		Participants received MK-2206 45 mg administered PO on Days 1, 3, 5, and 7 in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.	Participants received MK-2206 60 mg administered PO on Days 1, 3, 5, and 7 in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.	Participants received MK-2206 90 mg administered PO in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.	Participants received MK-2206 135 mg administered PO in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.	Participants received MK-2206 200 mg administered PO in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.	Participants received MK-2206 45 mg administered PO on Days 1, 3, 5, and 7 in combination with Docetaxel 75 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily.	Participants received MK-2206 90 mg administered PO on Day 1 in combination with Docetaxel 60 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily.	Participants received MK-2206 135 mg administered PO on Day 1 in combination with Docetaxel 60 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily.	Participants received MK-2206 200 mg administered PO on Day 1 in combination with Docetaxel 60 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily.	Participants received MK-2206 45 mg administered PO every other day (Days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19 and 21) in combination with Erlotinib 100 mg administered PO once every day of each 21-day cycle.	Participants received MK-2206 45 mg administered PO every other day (Days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19 and 21) in combination with Erlotinib 150 mg administered PO once every day of each 21-day cycle.	Participants received MK-2206 135 mg administered PO on Days 1, 8 and 15 in combination with Erlotinib 100 mg administered PO once every day of each 21-day cycle.	Participants received MK-2206 135 mg administered PO on Days 1, 8 and 15 in combination with Erlotinib 150 mg administered PO once every day of each 21-day cycle.	Total of all reporting groups
Overall Number of Baseline Participants		7	9	6	5	6	5	3	5	4	9	4	6	8	77
Baseline Analysis Population Description		All participants who were allocated to receive treatment.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	7 participants	9 participants	6 participants	5 participants	6 participants	5 participants	3 participants	5 participants	4 participants	9 participants	4 participants	6 participants	8 participants	77 participants
		51.6 (15.3)	58.4 (13.6)	56.2 (10.4)	63.6 (7.8)	38.8 (12.4)	57.4 (19.7)	64.7 (12.0)	57.4 (8.0)	54.0 (9.4)	61.6 (6.1)	61.0 (6.4)	55.7 (12.7)	54.1 (10.9)	56.2 (12.4)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	7 participants	9 participants	6 participants	5 participants	6 participants	5 participants	3 participants	5 participants	4 participants	9 participants	4 participants	6 participants	8 participants	77 participants
	Female	4 57.1%	6 66.7%	2 33.3%	4 80.0%	1 16.7%	2 40.0%	1 33.3%	4 80.0%	3 75.0%	2 22.2%	1 25.0%	2 33.3%	4 50.0%	36 46.8%
	Male	3 42.9%	3 33.3%	4 66.7%	1 20.0%	5 83.3%	3 60.0%	2 66.7%	1 20.0%	1 25.0%	7 77.8%	3 75.0%	4 66.7%	4 50.0%	41 53.2%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	7 participants	9 participants	6 participants	5 participants	6 participants	5 participants	3 participants	5 participants	4 participants	9 participants	4 participants	6 participants	8 participants	77 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 16.7%	1 20.0%	0 0.0%	0 0.0%	0 0.0%	1 11.1%	0 0.0%	0 0.0%	0 0.0%	3 3.9%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	1 11.1%	0 0.0%	0 0.0%	1 16.7%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	2 2.6%
	White	7 100.0%	8 88.9%	6 100.0%	5 100.0%	4 66.7%	4 80.0%	3 100.0%	5 100.0%	4 100.0%	8 88.9%	4 100.0%	6 100.0%	8 100.0%	72 93.5%
	More than one race	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1
Description	A DLT was any of the following deemed drug related by investigator and graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 criteria: Grade (G)4 hematologic toxicity lasting ≥7 days; G4 thrombocytopenia; G3 or 4 febrile neutropenia and/or infection requiring treatment; G3, 4, 5 non-hematologic toxicity(with the exception of G3 nausea, vomiting, diarrhea, dehydration, or hyperglycemia that as a result of inadequate compliance with supportive care measures; alopecia, inadequately treated hypersensitivity reactions G3 elevated transaminases of ≤1 week in duration); adverse experience (AE) leading to dose reduction; unresolved toxicity causing ≥3 week delay in treatment; ≥G3 hyperglycemia; persistent increases in QTc interval; clinically significant bradycardia; and missing MK-2206 doses due to toxicity. The number of participants who experienced a DLT is presented.
Time Frame	Cycle 1 (Up to 21 days)

Outcome Measure Data

Analysis Population Description

All participants that have received one dose of study treatment

Arm/Group Title	MK-2206 45 mg QOD+Carboplatin+Paclitaxel	MK-2206 60 mg QOD+Carboplatin+Paclitaxel	MK-2206 90 mg Q3W+Carboplatin+Paclitaxel	MK-2206 135 mg Q3W+Carboplatin+Paclitaxel	MK-2206 200 mg Q3W+Carboplatin+Paclitaxel	MK-2206 45 mg QOD+Docetaxel 75 mg/m^2	MK-2206 90 mg Q3W+Docetaxel 60 mg/m^2	MK-2206 135 mg Q3W+Docetaxel 60 mg/m^2	MK-2206 200 mg Q3W+Docetaxel 60 mg/m^2	MK-2206 45 mg QOD+Erlotinib 100 mg	MK-2206 45 mg QOD+Erlotinib 150 mg	MK-2206 135 mg QW+Erlotinib 100 mg	MK-2206 135 mg QW+Erlotinib 150 mg
Arm/Group Description:	Participants received MK-2206 45 mg administered PO on Days 1, 3, 5, and 7 in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.	Participants received MK-2206 60 mg administered PO on Days 1, 3, 5, and 7 in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.	Participants received MK-2206 90 mg administered PO in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.	Participants received MK-2206 135 mg administered PO in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.	Participants received MK-2206 200 mg administered PO in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.	Participants received MK-2206 45 mg administered PO on Days 1, 3, 5, and 7 in combination with Docetaxel 75 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily.	Participants received MK-2206 90 mg administered PO on Day 1 in combination with Docetaxel 60 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily.	Participants received MK-2206 135 mg administered PO on Day 1 in combination with Docetaxel 60 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily.	Participants received MK-2206 200 mg administered PO on Day 1 in combination with Docetaxel 60 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily.	Participants received MK-2206 45 mg administered PO every other day (Days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19 and 21) in combination with Erlotinib 100 mg administered PO once every day of each 21-day cycle.	Participants received MK-2206 45 mg administered PO every other day (Days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19 and 21) in combination with Erlotinib 150 mg administered PO once every day of each 21-day cycle.	Participants received MK-2206 135 mg administered PO on Days 1, 8 and 15 in combination with Erlotinib 100 mg administered PO once every day of each 21-day cycle.	Participants received MK-2206 135 mg administered PO on Days 1, 8 and 15 in combination with Erlotinib 150 mg administered PO once every day of each 21-day cycle.
Overall Number of Participants Analyzed	6	9	5	5	6	5	3	4	4	9	4	6	6
Measure Type: Count of Participants; Unit of Measure: Participants
	1 16.7%	2 22.2%	1 20.0%	1 20.0%	2 33.3%	3 60.0%	0 0.0%	0 0.0%	1 25.0%	2 22.2%	1 25.0%	0 0.0%	1 16.7%

2. Primary Outcome

Title	Maximum Tolerated Dose (MTD) of MK-2206 Administered Every Other Day (QOD) in Combination With Carboplatin and Paclitaxel
Description	Participants received MK-2206 (45 or 60 mg) administered PO on Days 1, 3, 5, and 7 in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle. The MTD was determined by the number of participants who experienced a dose limiting toxicity (DLT). DLT was defined using the NCI CTCAE version 3.0 criteria. See primary DLT outcome measure for the DLT definition. The MTD was defined as the dose level, at which the percentage of patients who experienced a DLT rate in Cycle 1 that was closest to 30%. A minimum of 13 participants were required to be enrolled per dose to calculate DLT. If the DLT threshold or enrollment quota per dose were not reached then the MTD could not be determined.
Time Frame	Cycle 1 (Up to 21 days)

Outcome Measure Data

Analysis Population Description

All participants who received MK-2206 QOD+carboplatin+paclitaxel and had a DLT in Cycle 1 or received 90% of the planned doses and completed all safety evaluations ≤21 days after the first administration of treatment without experiencing a DLT. MTD could not be determined according to pre-defined protocol criteria based on the enrollment number.

Arm/Group Title	MK-2206 Administered QOD+Carboplatin+Paclitaxel
Arm/Group Description:	Participants received MK-2206 45 mg or 60 mg administered PO on Days 1, 3, 5, and 7 in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.
Overall Number of Participants Analyzed	9
Measure Type: Number; Unit of Measure: mg
	NA [1]

[1]

MTD could not be determined

3. Primary Outcome

Title	MTD of MK-2206 Administered Every Three Weeks (Q3W) in Combination With Carboplatin and Paclitaxel
Description	Participants received MK-2206 (90, 135, or 200 mg) administered PO in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle. The MTD was determined by the number of participants who experienced a DLT. DLT was defined using the NCI CTCAE version 3.0 criteria. See primary DLT outcome measure for the DLT definition. The MTD was defined as the dose level, at which the percentage of patients who experienced a DLT rate in Cycle 1 that was closest to 30%. A minimum of 13 participants were required to be enrolled per dose to calculate DLT. If the DLT threshold or enrollment quota per dose were not reached then the MTD could not be determined.
Time Frame	Cycle 1 (up to 21 days)

Outcome Measure Data

Analysis Population Description

All participants who received MK-2206 Q3W+carboplatin+paclitaxel and had a DLT in Cycle 1 or received 90% of the planned doses and completed all safety evaluations ≤21 days after the first administration of treatment without experiencing a DLT. MTD could not be determined according to pre-defined protocol criteria based on the enrollment number.

Arm/Group Title	MK-2206 Administered Q3W+Carboplatin+Paclitaxel
Arm/Group Description:	Participants received MK-2206 90 mg, 135 mg, or 200 mg administered PO in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.
Overall Number of Participants Analyzed	15
Measure Type: Number; Unit of Measure: mg
	NA [1]

[1]

MTD could not be determined

4. Primary Outcome

Title	MTD of MK-2206 Administered QOD in Combination With Docetaxel
Description	Participants received MK-2206 45 mg administered PO on Days 1, 3, 5, and 7 in combination with Docetaxel 75 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily. The MTD was determined by the number of participants who experienced a DLT. DLT was defined using the NCI CTCAE version 3.0 criteria. See primary DLT outcome measure for the DLT definition. The MTD was defined as the dose level, at which the percentage of patients who experienced a DLT rate in Cycle 1 that was closest to 30%. A minimum of 13 participants were required to be enrolled per dose to calculate DLT. If the DLT threshold or enrollment quota per dose were not reached then the MTD could not be determined.
Time Frame	Cycle 1 (up to 21 days)

Outcome Measure Data

Analysis Population Description

All participants who received MK-2206 QOD+docetaxel and had a DLT in Cycle 1 or received 90% of the planned doses and completed all safety evaluations ≤21 days after the first administration of treatment without experiencing a DLT. MTD could not be determined according to pre-defined protocol criteria based on the enrollment number.

Arm/Group Title	MK-2206 Administered QOD+Docetaxel
Arm/Group Description:	Participants received MK-2206 45 mg administered PO on Days 1, 3, 5, and 7 in combination with Docetaxel 75 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily.
Overall Number of Participants Analyzed	5
Measure Type: Number; Unit of Measure: mg
	NA [1]

[1]

MTD could not be determined

5. Primary Outcome

Title	MTD of MK-2206 Administered Q3W in Combination With Docetaxel
Description	Participants received MK-2206 (90, 135, or 200 mg) administered PO on Day 1 in combination with Docetaxel 60 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily. The MTD was determined by the number of participants who experienced a DLT. DLT was defined using the NCI CTCAE version 3.0 criteria. See primary DLT outcome measure for the DLT definition. The MTD was defined as the dose level, at which the percentage of patients who experienced a DLT rate in Cycle 1 that was closest to 30%. A minimum of 13 participants were required to be enrolled per dose to calculate DLT. If the DLT threshold or enrollment quota per dose were not reached then the MTD could not be determined.
Time Frame	Cycle 1 (up to 21 days)

Outcome Measure Data

Analysis Population Description

All participants who received MK-2206 Q3W+docetaxel and had a DLT in Cycle 1 or received 90% of the planned doses and completed all safety evaluations ≤21 days after the first administration of treatment without experiencing a DLT. MTD could not be determined according to pre-defined protocol criteria based on the enrollment number.

Arm/Group Title	MK-2206 Administered Q3W+Docetaxel
Arm/Group Description:	Participants received MK-2206 90 mg, 135 mg or 200 mg administered PO on Day 1 in combination with Docetaxel 60 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily.
Overall Number of Participants Analyzed	10
Measure Type: Number; Unit of Measure: mg
	NA [1]

[1]

MTD could not be determined

6. Primary Outcome

Title	MTD of MK-2206 Administered QOD in Combination With Erlotinib
Description	Participants received MK-2206 45 mg administered PO every other day (Days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19 and 21) in combination with Erlotinib (100 or 150 mg) administered PO once every day of each 21-day cycle. The MTD was determined by the number of participants who experienced a DLT. DLT was defined using the NCI CTCAE version 3.0 criteria. See primary DLT outcome measure for the DLT definition. The MTD was defined as the dose level, at which the percentage of patients who experienced a DLT rate in Cycle 1 that was closest to 30%. A minimum of 13 participants were required to be enrolled per dose to calculate DLT. If the DLT threshold or enrollment quota per dose were not reached then the MTD could not be determined.
Time Frame	Cycle 1 (up to 21 days)

Outcome Measure Data

Analysis Population Description

All participants who received MK-2206 QOD+erlotinib and had a DLT in Cycle 1 or received 90% of the planned doses and completed all safety evaluations ≤21 days after the first administration of treatment without experiencing a DLT. MTD could not be determined according to pre-defined protocol criteria based on the enrollment number.

Arm/Group Title	MK-2206 Administered QOD+Erlotinib
Arm/Group Description:	Participants received MK-2206 45 mg administered PO every other day (Days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19 and 21) in combination with Erlotinib 100 mg or 150 mg administered PO once every day of each 21-day cycle.
Overall Number of Participants Analyzed	11
Measure Type: Number; Unit of Measure: mg
	NA [1]

[1]

MTD could not be determined

7. Primary Outcome

Title	MTD of MK-2206 Administered Once Every Week (QW) in Combination With Erlotinib
Description	Participants received MK-2206 135 mg administered PO on Days 1, 8 and 15 in combination with Erlotinib (100 or 150 mg) administered PO once every day of each 21-day cycle. The MTD was determined by the number of participants who experienced a DLT. DLT was defined using the NCI CTCAE version 3.0 criteria. See primary DLT outcome measure for the DLT definition. The MTD was defined as the dose level, at which the percentage of patients who experienced a DLT rate in Cycle 1 that was closest to 30%. A minimum of 13 participants were required to be enrolled per dose to calculate DLT. If the DLT threshold or enrollment quota per dose were not reached then the MTD could not be determined.
Time Frame	Cycle 1 (up to 21 days)

Outcome Measure Data

Analysis Population Description

All participants who received MK-2206 QW+erlotinib and had a DLT in Cycle 1 or received 90% of the planned doses and completed all safety evaluations ≤21 days after the first administration of treatment without experiencing a DLT. MTD could not be determined according to pre-defined protocol criteria based on the enrollment number.

Arm/Group Title	MK-2206 Administered QW+Erlotinib
Arm/Group Description:	Participants received MK-2206 135 mg administered PO on Days 1, 8 and 15 in combination with Erlotinib 100 mg or 150 mg administered PO once every day of each 21-day cycle.
Overall Number of Participants Analyzed	9
Measure Type: Number; Unit of Measure: mg
	NA [1]

[1]

MTD could not be determined

8. Primary Outcome

Title	Maximum Plasma Concentration of MK-2206 (Cmax)
Description	Blood samples are to be collected at specified time points according to arm and schedule: QOD schedule for MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48 hours(h) postdose); Q3W schedule MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48, 96h postdose); QOD schedule for the MK-2206+erlotinib (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose); and QW schedule for MK-2206+erlotinib (Cycles 1 Day 1: predose and 2, 4, 6, 10, 24, 48, 96h postdose) for the determination of MK-2206 Cmax after Dose 1. The Cmax of MK-2206 after Dose 1 will be presented.
Time Frame	At designated time points on Cycle 1 Day 1 (Up to 96 hours)

Outcome Measure Data

Analysis Population Description

All participants who received MK-2206 on Cycle 1 Day 1 and had blood samples drawn for the PK parameter being analyzed

Arm/Group Title	MK-2206 45 mg QOD+Carboplatin+Paclitaxel	MK-2206 60 mg QOD+Carboplatin+Paclitaxel	MK-2206 90 mg Q3W+Carboplatin+Paclitaxel	MK-2206 135 mg Q3W+Carboplatin+Paclitaxel	MK-2206 200 mg Q3W+Carboplatin+Paclitaxel	MK-2206 45 mg QOD+Docetaxel 75 mg/m^2	MK-2206 90 mg Q3W+Docetaxel 60 mg/m^2	MK-2206 135 mg Q3W+Docetaxel 60 mg/m^2	MK-2206 200 mg Q3W+Docetaxel 60 mg/m^2	MK-2206 45 mg QOD+Erlotinib 100 mg	MK-2206 45 mg QOD+Erlotinib 150 mg	MK-2206 135 mg QW+Erlotinib 100 mg	MK-2206 135 mg QW+Erlotinib 150 mg
Arm/Group Description:	Participants received MK-2206 45 mg administered PO on Days 1, 3, 5, and 7 in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.	Participants received MK-2206 60 mg administered PO on Days 1, 3, 5, and 7 in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.	Participants received MK-2206 90 mg administered PO in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.	Participants received MK-2206 135 mg administered PO in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.	Participants received MK-2206 200 mg administered PO in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.	Participants received MK-2206 45 mg administered PO on Days 1, 3, 5, and 7 in combination with Docetaxel 75 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily.	Participants received MK-2206 90 mg administered PO on Day 1 in combination with Docetaxel 60 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily.	Participants received MK-2206 135 mg administered PO on Day 1 in combination with Docetaxel 60 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily.	Participants received MK-2206 200 mg administered PO on Day 1 in combination with Docetaxel 60 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily.	Participants received MK-2206 45 mg administered PO every other day (Days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19 and 21) in combination with Erlotinib 100 mg administered PO once every day of each 21-day cycle.	Participants received MK-2206 45 mg administered PO every other day (Days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19 and 21) in combination with Erlotinib 150 mg administered PO once every day of each 21-day cycle.	Participants received MK-2206 135 mg administered PO on Days 1, 8 and 15 in combination with Erlotinib 100 mg administered PO once every day of each 21-day cycle.	Participants received MK-2206 135 mg administered PO on Days 1, 8 and 15 in combination with Erlotinib 150 mg administered PO once every day of each 21-day cycle.
Overall Number of Participants Analyzed	6	8	5	5	6	5	3	3	4	9	4	6	6
Mean (Standard Deviation); Unit of Measure: nmol/L
	57.7 (13.8)	88.3 (24.2)	144 (57.0)	247 (52.5)	431 (249)	42.9 (13.3)	106 (42.5)	278 (35.5)	287 (67.6)	48.8 (11.2)	65.6 (29.3)	212 (75.9)	244 (84.2)

9. Primary Outcome

Title	Time to Maximum Plasma Concentration of MK-2206 (Tmax)
Description	Blood samples are to be collected at specified time points according to arm and schedule: QOD schedule for MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48 hours(h) postdose); Q3W schedule MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48, 96h postdose); QOD schedule for the MK-2206+erlotinib (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose); and QW schedule for MK-2206+erlotinib (Cycles 1 Day 1: predose and 2, 4, 6, 10, 24, 48, 96h postdose) for the determination of MK-2206 Tmax after Dose 1. The Tmax of MK-2206 after Dose 1 will be presented.
Time Frame	At designated time points on Cycle 1 Day 1 (Up to 96 hours)

Outcome Measure Data

Analysis Population Description

All participants who received MK-2206 on Cycle 1 Day 1 and had blood samples drawn for the PK parameter being analyzed

Arm/Group Title	MK-2206 45 mg QOD+Carboplatin+Paclitaxel	MK-2206 60 mg QOD+Carboplatin+Paclitaxel	MK-2206 90 mg Q3W+Carboplatin+Paclitaxel	MK-2206 135 mg Q3W+Carboplatin+Paclitaxel	MK-2206 200 mg Q3W+Carboplatin+Paclitaxel	MK-2206 45 mg QOD+Docetaxel 75 mg/m^2	MK-2206 90 mg Q3W+Docetaxel 60 mg/m^2	MK-2206 135 mg Q3W+Docetaxel 60 mg/m^2	MK-2206 200 mg Q3W+Docetaxel 60 mg/m^2	MK-2206 45 mg QOD+Erlotinib 100 mg	MK-2206 45 mg QOD+Erlotinib 150 mg	MK-2206 135 mg QW+Erlotinib 100 mg	MK-2206 135 mg QW+Erlotinib 150 mg
Arm/Group Description:	Participants received MK-2206 45 mg administered PO on Days 1, 3, 5, and 7 in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.	Participants received MK-2206 60 mg administered PO on Days 1, 3, 5, and 7 in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.	Participants received MK-2206 90 mg administered PO in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.	Participants received MK-2206 135 mg administered PO in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.	Participants received MK-2206 200 mg administered PO in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.	Participants received MK-2206 45 mg administered PO on Days 1, 3, 5, and 7 in combination with Docetaxel 75 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily.	Participants received MK-2206 90 mg administered PO on Day 1 in combination with Docetaxel 60 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily.	Participants received MK-2206 135 mg administered PO on Day 1 in combination with Docetaxel 60 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily.	Participants received MK-2206 200 mg administered PO on Day 1 in combination with Docetaxel 60 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily.	Participants received MK-2206 45 mg administered PO every other day (Days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19 and 21) in combination with Erlotinib 100 mg administered PO once every day of each 21-day cycle.	Participants received MK-2206 45 mg administered PO every other day (Days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19 and 21) in combination with Erlotinib 150 mg administered PO once every day of each 21-day cycle.	Participants received MK-2206 135 mg administered PO on Days 1, 8 and 15 in combination with Erlotinib 100 mg administered PO once every day of each 21-day cycle.	Participants received MK-2206 135 mg administered PO on Days 1, 8 and 15 in combination with Erlotinib 150 mg administered PO once every day of each 21-day cycle.
Overall Number of Participants Analyzed	6	8	5	5	6	5	3	3	4	9	4	6	6
Median (Full Range); Unit of Measure: hours
	4.0; (4.0 to 6.0)	8.0; (6.0 to 10.0)	6.0; (4.0 to 10.0)	10.0; (6.0 to 10.0)	5.0; (4.0 to 10.0)	6.0; (4.0 to 10.0)	4.0; (4.0 to 10.0)	6.0; (4.0 to 10.0)	6.0; (4.0 to 6.0)	6.0; (4.0 to 10.0)	7.0; (4.0 to 24.0)	6.0; (2.0 to 6.0)	4.0; (4.0 to 10.0)

10. Primary Outcome

Title	Minimum Plasma Concentration of MK-2206 (Ctrough)
Description	Blood samples are to be collected at specified time points according to arm and schedule: QOD schedule for MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48 hours(h) postdose); Q3W schedule MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose); QOD schedule for the MK-2206+erlotinib (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose); and QW schedule for MK-2206+erlotinib (Cycles 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose) for the determination of MK-2206 Ctrough after Dose 1. The Ctrough after Dose 1 is presented and is the 48-hour postdose concentration.
Time Frame	At designated time points on Cycle 1 Day 1 (Up to 48 hours)

Outcome Measure Data

Analysis Population Description

All participants who received MK-2206 on Cycle 1 Day 1 and had blood samples drawn for the PK parameter being analyzed

Arm/Group Title	MK-2206 45 mg QOD+Carboplatin+Paclitaxel	MK-2206 60 mg QOD+Carboplatin+Paclitaxel	MK-2206 90 mg Q3W+Carboplatin+Paclitaxel	MK-2206 135 mg Q3W+Carboplatin+Paclitaxel	MK-2206 200 mg Q3W+Carboplatin+Paclitaxel	MK-2206 45 mg QOD+Docetaxel 75 mg/m^2	MK-2206 90 mg Q3W+Docetaxel 60 mg/m^2	MK-2206 135 mg Q3W+Docetaxel 60 mg/m^2	MK-2206 200 mg Q3W+Docetaxel 60 mg/m^2	MK-2206 45 mg QOD+Erlotinib 100 mg	MK-2206 45 mg QOD+Erlotinib 150 mg	MK-2206 135 mg QW+Erlotinib 100 mg	MK-2206 135 mg QW+Erlotinib 150 mg
Arm/Group Description:	Participants received MK-2206 45 mg administered PO on Days 1, 3, 5, and 7 in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.	Participants received MK-2206 60 mg administered PO on Days 1, 3, 5, and 7 in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.	Participants received MK-2206 90 mg administered PO in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.	Participants received MK-2206 135 mg administered PO in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.	Participants received MK-2206 200 mg administered PO in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.	Participants received MK-2206 45 mg administered PO on Days 1, 3, 5, and 7 in combination with Docetaxel 75 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily.	Participants received MK-2206 90 mg administered PO on Day 1 in combination with Docetaxel 60 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily.	Participants received MK-2206 135 mg administered PO on Day 1 in combination with Docetaxel 60 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily.	Participants received MK-2206 200 mg administered PO on Day 1 in combination with Docetaxel 60 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily.	Participants received MK-2206 45 mg administered PO every other day (Days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19 and 21) in combination with Erlotinib 100 mg administered PO once every day of each 21-day cycle.	Participants received MK-2206 45 mg administered PO every other day (Days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19 and 21) in combination with Erlotinib 150 mg administered PO once every day of each 21-day cycle.	Participants received MK-2206 135 mg administered PO on Days 1, 8 and 15 in combination with Erlotinib 100 mg administered PO once every day of each 21-day cycle.	Participants received MK-2206 135 mg administered PO on Days 1, 8 and 15 in combination with Erlotinib 150 mg administered PO once every day of each 21-day cycle.
Overall Number of Participants Analyzed	6	8	5	5	6	5	3	1	4	9	4	6	6
Mean (Standard Deviation); Unit of Measure: nmol/L
	24.9 (10.7)	40.6 (11.2)	1.36 (0.898)	4.67 (3.33)	2.21 (1.04)	17.1 (3.66)	2.27 (1.04)	3.80 [1] (NA)	3.24 (0.638)	23.8 (8.12)	36.8 (10.6)	96.6 (43.6)	95.5 (43.1)

[1]

Standard deviation could not be calculated for 1 participant

11. Primary Outcome

Title	Area Under the MK-2206 Concentration Versus Time Curve From Time Zero to 48 Hours Postdose (AUC 0-48h)
Description	Blood samples are to be collected at specified time points according to arm and schedule: QOD schedule for MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48 hours(h) postdose); Q3W schedule MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose); QOD schedule for the MK-2206+erlotinib (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose); and QW schedule for MK-2206+erlotinib (Cycles 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose) for the determination of MK-2206 AUC0-48h after Dose 1. The AUC0-48h after Dose 1 is presented.
Time Frame	At designated time points on Cycle 1 Day 1 (Up to 48 hours)

Outcome Measure Data

Analysis Population Description

All participants who received MK-2206 on Cycle 1 Day 1 and had blood samples drawn for the PK parameter being analyzed

Arm/Group Title	MK-2206 45 mg QOD+Carboplatin+Paclitaxel	MK-2206 60 mg QOD+Carboplatin+Paclitaxel	MK-2206 90 mg Q3W+Carboplatin+Paclitaxel	MK-2206 135 mg Q3W+Carboplatin+Paclitaxel	MK-2206 200 mg Q3W+Carboplatin+Paclitaxel	MK-2206 45 mg QOD+Docetaxel 75 mg/m^2	MK-2206 90 mg Q3W+Docetaxel 60 mg/m^2	MK-2206 135 mg Q3W+Docetaxel 60 mg/m^2	MK-2206 200 mg Q3W+Docetaxel 60 mg/m^2	MK-2206 45 mg QOD+Erlotinib 100 mg	MK-2206 45 mg QOD+Erlotinib 150 mg	MK-2206 135 mg QW+Erlotinib 100 mg	MK-2206 135 mg QW+Erlotinib 150 mg
Arm/Group Description:	Participants received MK-2206 45 mg administered PO on Days 1, 3, 5, and 7 in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.	Participants received MK-2206 60 mg administered PO on Days 1, 3, 5, and 7 in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.	Participants received MK-2206 90 mg administered PO in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.	Participants received MK-2206 135 mg administered PO in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.	Participants received MK-2206 200 mg administered PO in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.	Participants received MK-2206 45 mg administered PO on Days 1, 3, 5, and 7 in combination with Docetaxel 75 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily.	Participants received MK-2206 90 mg administered PO on Day 1 in combination with Docetaxel 60 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily.	Participants received MK-2206 135 mg administered PO on Day 1 in combination with Docetaxel 60 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily.	Participants received MK-2206 200 mg administered PO on Day 1 in combination with Docetaxel 60 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily.	Participants received MK-2206 45 mg administered PO every other day (Days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19 and 21) in combination with Erlotinib 100 mg administered PO once every day of each 21-day cycle.	Participants received MK-2206 45 mg administered PO every other day (Days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19 and 21) in combination with Erlotinib 150 mg administered PO once every day of each 21-day cycle.	Participants received MK-2206 135 mg administered PO on Days 1, 8 and 15 in combination with Erlotinib 100 mg administered PO once every day of each 21-day cycle.	Participants received MK-2206 135 mg administered PO on Days 1, 8 and 15 in combination with Erlotinib 150 mg administered PO once every day of each 21-day cycle.
Overall Number of Participants Analyzed	6	8	5	5	6	5	3	3	4	9	4	6	6
Mean (Standard Deviation); Unit of Measure: nmol•hr/L
	1630 (496)	2700 (619)	4130 (1520)	7420 (1250)	9730 (2320)	1320 (395)	3000 (1250)	8090 (542)	7690 (1550)	1460 (417)	2110 (637)	6420 (2760)	6560 (2650)

12. Secondary Outcome

Title	Number of Participants Who Had a Tumor Response of Complete Response (CR) or Partial Response (PR)
Description	Tumor response was assessed using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) and was recorded from the start of the study treatment until the end of treatment. Response categories included: Complete Response (CR): disappearance of all target lesions and Partial Response (PR): at least a 30% decrease in the sum of diameters of target lesions. The number of participants who had a tumor response of either CR or PR is presented.
Time Frame	Up to approximately 4 months (6 cycles)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study treatment and had measurable disease at baseline.

Arm/Group Title	MK-2206 45 mg QOD+Carboplatin+Paclitaxel	MK-2206 60 mg QOD+Carboplatin+Paclitaxel	MK-2206 90 mg Q3W+Carboplatin+Paclitaxel	MK-2206 135 mg Q3W+Carboplatin+Paclitaxel	MK-2206 200 mg Q3W+Carboplatin+Paclitaxel	MK-2206 45 mg QOD+Docetaxel 75 mg/m^2	MK-2206 90 mg Q3W+Docetaxel 60 mg/m^2	MK-2206 135 mg Q3W+Docetaxel 60 mg/m^2	MK-2206 200 mg Q3W+Docetaxel 60 mg/m^2	MK-2206 45 mg QOD+Erlotinib 100 mg	MK-2206 45 mg QOD+Erlotinib 150 mg	MK-2206 135 mg QW+Erlotinib 100 mg	MK-2206 135 mg QW+Erlotinib 150 mg
Arm/Group Description:	Participants received MK-2206 45 mg administered PO on Days 1, 3, 5, and 7 in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.	Participants received MK-2206 60 mg administered PO on Days 1, 3, 5, and 7 in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.	Participants received MK-2206 90 mg administered PO in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.	Participants received MK-2206 135 mg administered PO in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.	Participants received MK-2206 200 mg administered PO in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.	Participants received MK-2206 45 mg administered PO on Days 1, 3, 5, and 7 in combination with Docetaxel 75 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily.	Participants received MK-2206 90 mg administered PO on Day 1 in combination with Docetaxel 60 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily.	Participants received MK-2206 135 mg administered PO on Day 1 in combination with Docetaxel 60 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily.	Participants received MK-2206 200 mg administered PO on Day 1 in combination with Docetaxel 60 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily.	Participants received MK-2206 45 mg administered PO every other day (Days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19 and 21) in combination with Erlotinib 100 mg administered PO once every day of each 21-day cycle.	Participants received MK-2206 45 mg administered PO every other day (Days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19 and 21) in combination with Erlotinib 150 mg administered PO once every day of each 21-day cycle.	Participants received MK-2206 135 mg administered PO on Days 1, 8 and 15 in combination with Erlotinib 100 mg administered PO once every day of each 21-day cycle.	Participants received MK-2206 135 mg administered PO on Days 1, 8 and 15 in combination with Erlotinib 150 mg administered PO once every day of each 21-day cycle.
Overall Number of Participants Analyzed	6	9	5	5	6	5	3	4	4	9	4	6	6
Measure Type: Count of Participants; Unit of Measure: Participants
	1 16.7%	3 33.3%	0 0.0%	1 20.0%	1 16.7%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%

Adverse Events

Time Frame	Up to approximately 14 months (Up to 30 days after last dose of study treatment)
Adverse Event Reporting Description	All participants who received at least one dose of study treatment
Arm/Group Title	MK-2206 45 mg QOD+Carboplatin+Paclitaxel		MK-2206 60 mg QOD+Carboplatin+Paclitaxel		MK-2206 90 mg Q3W+Carboplatin+Paclitaxel		MK-2206 135 mg Q3W+Carboplatin+Paclitaxel		MK-2206 200 mg Q3W+Carboplatin+Paclitaxel		MK-2206 45 mg QOD+Docetaxel 75 mg/m2		MK-2206 90 mg Q3W+Docetaxel 60 mg/m2		MK-2206 135 mg Q3W+Docetaxel 60 mg/m2		MK-2206 200 mg Q3W+Docetaxel 60 mg/m2		MK-2206 45 mg QOD+Erlotinib 100 mg		MK-2206 45 mg QOD+Erlotinib 150 mg		MK-2206 135 mg QW+Erlotinib 100 mg		MK-2206 135 mg QW+Erlotinib 150 mg
Arm/Group Description	Participants received MK-2206 45 mg administered PO on Days 1, 3, 5, and 7 in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.		Participants received MK-2206 60 mg administered PO on Days 1, 3, 5, and 7 in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.		Participants received MK-2206 90 mg administered PO in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.		Participants received MK-2206 135 mg administered PO in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.		Participants received MK-2206 200 mg administered PO in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle.		Participants received MK-2206 45 mg administered PO on Days 1, 3, 5, and 7 in combination with Docetaxel 75 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily.		Participants received MK-2206 90 mg administered PO on Day 1 in combination with Docetaxel 60 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily.		Participants received MK-2206 135 mg administered PO on Day 1 in combination with Docetaxel 60 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily.		Participants received MK-2206 200 mg administered PO on Day 1 in combination with Docetaxel 60 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily.		Participants received MK-2206 45 mg administered PO every other day (Days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19 and 21) in combination with Erlotinib 100 mg administered PO once every day of each 21-day cycle.		Participants received MK-2206 45 mg administered PO every other day (Days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19 and 21) in combination with Erlotinib 150 mg administered PO once every day of each 21-day cycle.		Participants received MK-2206 135 mg administered PO on Days 1, 8 and 15 in combination with Erlotinib 100 mg administered PO once every day of each 21-day cycle.		Participants received MK-2206 135 mg administered PO on Days 1, 8 and 15 in combination with Erlotinib 150 mg administered PO once every day of each 21-day cycle.
All-Cause Mortality
	MK-2206 45 mg QOD+Carboplatin+Paclitaxel		MK-2206 60 mg QOD+Carboplatin+Paclitaxel		MK-2206 90 mg Q3W+Carboplatin+Paclitaxel		MK-2206 135 mg Q3W+Carboplatin+Paclitaxel		MK-2206 200 mg Q3W+Carboplatin+Paclitaxel		MK-2206 45 mg QOD+Docetaxel 75 mg/m2		MK-2206 90 mg Q3W+Docetaxel 60 mg/m2		MK-2206 135 mg Q3W+Docetaxel 60 mg/m2		MK-2206 200 mg Q3W+Docetaxel 60 mg/m2		MK-2206 45 mg QOD+Erlotinib 100 mg		MK-2206 45 mg QOD+Erlotinib 150 mg		MK-2206 135 mg QW+Erlotinib 100 mg		MK-2206 135 mg QW+Erlotinib 150 mg
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	0/6 (0.00%)		1/9 (11.11%)		0/5 (0.00%)		0/5 (0.00%)		0/6 (0.00%)		1/5 (20.00%)		0/3 (0.00%)		0/4 (0.00%)		0/4 (0.00%)		1/9 (11.11%)		0/4 (0.00%)		1/6 (16.67%)		1/6 (16.67%)
Serious Adverse Events
	MK-2206 45 mg QOD+Carboplatin+Paclitaxel		MK-2206 60 mg QOD+Carboplatin+Paclitaxel		MK-2206 90 mg Q3W+Carboplatin+Paclitaxel		MK-2206 135 mg Q3W+Carboplatin+Paclitaxel		MK-2206 200 mg Q3W+Carboplatin+Paclitaxel		MK-2206 45 mg QOD+Docetaxel 75 mg/m2		MK-2206 90 mg Q3W+Docetaxel 60 mg/m2		MK-2206 135 mg Q3W+Docetaxel 60 mg/m2		MK-2206 200 mg Q3W+Docetaxel 60 mg/m2		MK-2206 45 mg QOD+Erlotinib 100 mg		MK-2206 45 mg QOD+Erlotinib 150 mg		MK-2206 135 mg QW+Erlotinib 100 mg		MK-2206 135 mg QW+Erlotinib 150 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/6 (33.33%)		8/9 (88.89%)		3/5 (60.00%)		1/5 (20.00%)		2/6 (33.33%)		5/5 (100.00%)		1/3 (33.33%)		3/4 (75.00%)		3/4 (75.00%)		6/9 (66.67%)		1/4 (25.00%)		4/6 (66.67%)		5/6 (83.33%)
Blood and lymphatic system disorders
Anaemia † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	2/9 (22.22%)	2	0/4 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1
Febrile neutropenia † 1	0/6 (0.00%)	0	2/9 (22.22%)	2	1/5 (20.00%)	1	0/5 (0.00%)	0	0/6 (0.00%)	0	3/5 (60.00%)	3	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Neutropenia † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	1/5 (20.00%)	1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Thrombocytopenia † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	1/5 (20.00%)	1	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Cardiac disorders
Sinus tachycardia † 1	1/6 (16.67%)	1	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Ear and labyrinth disorders
Tinnitus † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	1/4 (25.00%)	1	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Eye disorders
Retinal vein occlusion † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	1/3 (33.33%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Gastrointestinal disorders
Abdominal pain † 1	1/6 (16.67%)	1	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	1/4 (25.00%)	1	1/4 (25.00%)	1	1/9 (11.11%)	2	0/4 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1
Constipation † 1	0/6 (0.00%)	0	1/9 (11.11%)	1	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Diarrhoea † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	1/9 (11.11%)	1	0/4 (0.00%)	0	0/6 (0.00%)	0	2/6 (33.33%)	2
Nausea † 1	0/6 (0.00%)	0	1/9 (11.11%)	1	1/5 (20.00%)	1	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	1/9 (11.11%)	1	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Small intestinal obstruction † 1	0/6 (0.00%)	0	1/9 (11.11%)	1	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Stomatitis † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	2/6 (33.33%)	2
Vomiting † 1	0/6 (0.00%)	0	1/9 (11.11%)	1	1/5 (20.00%)	1	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0
General disorders
Fatigue † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0
Pyrexia † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	2/6 (33.33%)	2	1/6 (16.67%)	1
Hepatobiliary disorders
Hyperbilirubinaemia † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0
Immune system disorders
Hypersensitivity † 1	0/6 (0.00%)	0	1/9 (11.11%)	1	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Infections and infestations
Cellulitis † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	1/9 (11.11%)	1	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Infection † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	1/4 (25.00%)	1	0/6 (0.00%)	0	1/6 (16.67%)	1
Lower respiratory tract infection † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0
Neutropenic sepsis † 1	0/6 (0.00%)	0	1/9 (11.11%)	1	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	1/4 (25.00%)	1	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Pneumonia † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	1/9 (11.11%)	1	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Urinary tract infection † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	1/5 (20.00%)	1	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Injury, poisoning and procedural complications
Hip fracture † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	1/5 (20.00%)	1	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Infusion related reaction † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	1/4 (25.00%)	1	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Investigations
Blood creatinine increased † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	1/9 (11.11%)	1	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Transaminases increased † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	1/9 (11.11%)	1	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Metabolism and nutrition disorders
Decreased appetite † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0
Dehydration † 1	0/6 (0.00%)	0	1/9 (11.11%)	1	0/5 (0.00%)	0	0/5 (0.00%)	0	1/6 (16.67%)	1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	1/4 (25.00%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0
Hypercalcaemia † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	1/5 (20.00%)	1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Hypokalaemia † 1	0/6 (0.00%)	0	1/9 (11.11%)	1	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1
Hyponatraemia † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	1/4 (25.00%)	1	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Musculoskeletal and connective tissue disorders
Musculoskeletal pain † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1
Pathological fracture † 1	0/6 (0.00%)	0	1/9 (11.11%)	1	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm malignant † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	1/5 (20.00%)	1	0/3 (0.00%)	0	1/4 (25.00%)	1	0/4 (0.00%)	0	1/9 (11.11%)	1	0/4 (0.00%)	0	1/6 (16.67%)	1	1/6 (16.67%)	1
Nervous system disorders
Headache † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	1/6 (16.67%)	1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Spinal cord compression † 1	0/6 (0.00%)	0	1/9 (11.11%)	1	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Renal and urinary disorders
Renal failure acute † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	1/4 (25.00%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0
Reproductive system and breast disorders
Pelvic pain † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1
Respiratory, thoracic and mediastinal disorders
Bronchial obstruction † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0
Cough † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0
Dyspnoea † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	1/4 (25.00%)	1	1/6 (16.67%)	1	0/6 (0.00%)	0
Hypoxia † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1
Pleural effusion † 1	0/6 (0.00%)	0	1/9 (11.11%)	1	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	2/5 (40.00%)	2	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Skin and subcutaneous tissue disorders
Rash † 1	0/6 (0.00%)	0	1/9 (11.11%)	1	1/5 (20.00%)	1	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1
1 Term from vocabulary, MedDRA 13.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	MK-2206 45 mg QOD+Carboplatin+Paclitaxel		MK-2206 60 mg QOD+Carboplatin+Paclitaxel		MK-2206 90 mg Q3W+Carboplatin+Paclitaxel		MK-2206 135 mg Q3W+Carboplatin+Paclitaxel		MK-2206 200 mg Q3W+Carboplatin+Paclitaxel		MK-2206 45 mg QOD+Docetaxel 75 mg/m2		MK-2206 90 mg Q3W+Docetaxel 60 mg/m2		MK-2206 135 mg Q3W+Docetaxel 60 mg/m2		MK-2206 200 mg Q3W+Docetaxel 60 mg/m2		MK-2206 45 mg QOD+Erlotinib 100 mg		MK-2206 45 mg QOD+Erlotinib 150 mg		MK-2206 135 mg QW+Erlotinib 100 mg		MK-2206 135 mg QW+Erlotinib 150 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/6 (100.00%)		8/9 (88.89%)		5/5 (100.00%)		5/5 (100.00%)		5/6 (83.33%)		5/5 (100.00%)		3/3 (100.00%)		3/4 (75.00%)		4/4 (100.00%)		9/9 (100.00%)		4/4 (100.00%)		6/6 (100.00%)		6/6 (100.00%)
Blood and lymphatic system disorders
Anaemia † 1	2/6 (33.33%)	2	5/9 (55.56%)	11	3/5 (60.00%)	3	3/5 (60.00%)	3	1/6 (16.67%)	1	2/5 (40.00%)	7	0/3 (0.00%)	0	1/4 (25.00%)	1	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	1/6 (16.67%)	1	3/6 (50.00%)	3
Leukopenia † 1	1/6 (16.67%)	1	6/9 (66.67%)	23	4/5 (80.00%)	9	4/5 (80.00%)	4	1/6 (16.67%)	1	1/5 (20.00%)	3	1/3 (33.33%)	2	0/4 (0.00%)	0	1/4 (25.00%)	1	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Lymphopenia † 1	0/6 (0.00%)	0	3/9 (33.33%)	12	1/5 (20.00%)	1	1/5 (20.00%)	1	0/6 (0.00%)	0	2/5 (40.00%)	7	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	1/9 (11.11%)	4	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Neutropenia † 1	1/6 (16.67%)	1	5/9 (55.56%)	13	4/5 (80.00%)	13	3/5 (60.00%)	3	1/6 (16.67%)	1	3/5 (60.00%)	8	2/3 (66.67%)	6	0/4 (0.00%)	0	1/4 (25.00%)	1	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Thrombocytopenia † 1	1/6 (16.67%)	1	5/9 (55.56%)	10	3/5 (60.00%)	6	2/5 (40.00%)	2	1/6 (16.67%)	1	2/5 (40.00%)	7	1/3 (33.33%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1
Cardiac disorders
Bradycardia † 1	0/6 (0.00%)	0	1/9 (11.11%)	1	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Sinus tachycardia † 1	0/6 (0.00%)	0	1/9 (11.11%)	1	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Ear and labyrinth disorders
Hyperacusis † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	1/6 (16.67%)	1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Meniere's disease † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	1/5 (20.00%)	1	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Tinnitus † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	1/6 (16.67%)	1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Endocrine disorders
Hypothyroidism † 1	0/6 (0.00%)	0	2/9 (22.22%)	2	2/5 (40.00%)	2	0/5 (0.00%)	0	1/6 (16.67%)	1	0/5 (0.00%)	0	0/3 (0.00%)	0	1/4 (25.00%)	1	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Eye disorders
Conjunctivitis † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	1/3 (33.33%)	1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/9 (11.11%)	1	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Diplopia † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	1/6 (16.67%)	1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	1/4 (25.00%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0
Dry eye † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	1/6 (16.67%)	1	1/6 (16.67%)	1
Eye irritation † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	1/4 (25.00%)	1	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Lacrimation increased † 1	1/6 (16.67%)	1	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0
Orbital oedema † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1
Photophobia † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	1/6 (16.67%)	1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Vision blurred † 1	1/6 (16.67%)	1	1/9 (11.11%)	1	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Visual impairment † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	2/6 (33.33%)	2
Gastrointestinal disorders
Abdominal discomfort † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1
Abdominal distension † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0
Abdominal pain † 1	0/6 (0.00%)	0	1/9 (11.11%)	1	0/5 (0.00%)	0	1/5 (20.00%)	1	1/6 (16.67%)	1	2/5 (40.00%)	2	0/3 (0.00%)	0	0/4 (0.00%)	0	1/4 (25.00%)	1	0/9 (0.00%)	0	1/4 (25.00%)	1	1/6 (16.67%)	1	1/6 (16.67%)	1
Abdominal pain upper † 1	0/6 (0.00%)	0	2/9 (22.22%)	2	1/5 (20.00%)	1	1/5 (20.00%)	1	0/6 (0.00%)	0	0/5 (0.00%)	0	1/3 (33.33%)	2	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	1/4 (25.00%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0
Ascites † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0
Cheilitis † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	2/6 (33.33%)	2	0/6 (0.00%)	0
Colitis † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	1/4 (25.00%)	1	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Constipation † 1	2/6 (33.33%)	2	1/9 (11.11%)	1	2/5 (40.00%)	3	2/5 (40.00%)	2	2/6 (33.33%)	2	1/5 (20.00%)	1	1/3 (33.33%)	1	0/4 (0.00%)	0	1/4 (25.00%)	1	1/9 (11.11%)	1	0/4 (0.00%)	0	0/6 (0.00%)	0	3/6 (50.00%)	3
Diarrhoea † 1	1/6 (16.67%)	2	4/9 (44.44%)	6	2/5 (40.00%)	2	1/5 (20.00%)	1	2/6 (33.33%)	3	1/5 (20.00%)	1	2/3 (66.67%)	2	0/4 (0.00%)	0	2/4 (50.00%)	2	5/9 (55.56%)	7	3/4 (75.00%)	5	4/6 (66.67%)	6	5/6 (83.33%)	7
Dry mouth † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	1/6 (16.67%)	1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	1/4 (25.00%)	2	0/6 (0.00%)	0	1/6 (16.67%)	1
Dyspepsia † 1	0/6 (0.00%)	0	1/9 (11.11%)	1	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	1/6 (16.67%)	1	1/6 (16.67%)	1
Dysphagia † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	1/4 (25.00%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0
Gastrointestinal haemorrhage † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	1/4 (25.00%)	1	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Gastrooesophageal reflux disease † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	1/5 (20.00%)	1	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Haematemesis † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1
Ileus † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	1/6 (16.67%)	1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Lip ulceration † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	1/4 (25.00%)	1	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Melaena † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	1/4 (25.00%)	1	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Mouth ulceration † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	1/4 (25.00%)	1	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Nausea † 1	3/6 (50.00%)	4	6/9 (66.67%)	6	3/5 (60.00%)	4	2/5 (40.00%)	2	4/6 (66.67%)	6	2/5 (40.00%)	2	1/3 (33.33%)	1	1/4 (25.00%)	1	2/4 (50.00%)	3	3/9 (33.33%)	5	4/4 (100.00%)	4	1/6 (16.67%)	3	2/6 (33.33%)	2
Oral pain † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	2/6 (33.33%)	2
Post-tussive vomiting † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	1/5 (20.00%)	1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Rectal haemorrhage † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	1/5 (20.00%)	1	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Rectal tenesmus † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1
Steatorrhoea † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1
Stomatitis † 1	1/6 (16.67%)	1	2/9 (22.22%)	3	2/5 (40.00%)	2	1/5 (20.00%)	1	1/6 (16.67%)	1	2/5 (40.00%)	2	0/3 (0.00%)	0	1/4 (25.00%)	1	0/4 (0.00%)	0	4/9 (44.44%)	6	1/4 (25.00%)	1	4/6 (66.67%)	11	3/6 (50.00%)	4
Toothache † 1	1/6 (16.67%)	1	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Vomiting † 1	1/6 (16.67%)	2	3/9 (33.33%)	4	1/5 (20.00%)	1	3/5 (60.00%)	3	4/6 (66.67%)	5	3/5 (60.00%)	4	1/3 (33.33%)	1	1/4 (25.00%)	1	1/4 (25.00%)	2	4/9 (44.44%)	5	1/4 (25.00%)	1	1/6 (16.67%)	1	0/6 (0.00%)	0
General disorders
Application site erythema † 1	0/6 (0.00%)	0	1/9 (11.11%)	1	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Asthenia † 1	0/6 (0.00%)	0	1/9 (11.11%)	1	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	1/3 (33.33%)	2	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Catheter site swelling † 1	0/6 (0.00%)	0	1/9 (11.11%)	1	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Chest discomfort † 1	1/6 (16.67%)	1	1/9 (11.11%)	1	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Chest pain † 1	1/6 (16.67%)	1	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	1/4 (25.00%)	1	1/9 (11.11%)	5	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Chills † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	1/5 (20.00%)	1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	1/9 (11.11%)	1	0/4 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1
Early satiety † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	1/4 (25.00%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0
Fatigue † 1	4/6 (66.67%)	5	6/9 (66.67%)	7	4/5 (80.00%)	8	5/5 (100.00%)	5	1/6 (16.67%)	1	4/5 (80.00%)	4	3/3 (100.00%)	4	2/4 (50.00%)	2	4/4 (100.00%)	4	5/9 (55.56%)	5	3/4 (75.00%)	3	3/6 (50.00%)	3	4/6 (66.67%)	5
Influenza like illness † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	2
Malaise † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	1/5 (20.00%)	1	0/5 (0.00%)	0	1/6 (16.67%)	3	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	1/4 (25.00%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0
Mucosal inflammation † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	1/4 (25.00%)	2	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Oedema † 1	1/6 (16.67%)	1	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Oedema peripheral † 1	1/6 (16.67%)	1	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	2/5 (40.00%)	2	1/3 (33.33%)	1	0/4 (0.00%)	0	1/4 (25.00%)	1	2/9 (22.22%)	2	1/4 (25.00%)	1	0/6 (0.00%)	0	1/6 (16.67%)	1
Pain † 1	0/6 (0.00%)	0	1/9 (11.11%)	1	0/5 (0.00%)	0	0/5 (0.00%)	0	1/6 (16.67%)	2	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	1/9 (11.11%)	1	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Pyrexia † 1	2/6 (33.33%)	4	3/9 (33.33%)	3	0/5 (0.00%)	0	0/5 (0.00%)	0	1/6 (16.67%)	1	2/5 (40.00%)	2	0/3 (0.00%)	0	0/4 (0.00%)	0	1/4 (25.00%)	1	2/9 (22.22%)	2	0/4 (0.00%)	0	1/6 (16.67%)	1	3/6 (50.00%)	3
Thirst † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1
Ulcer † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	1/5 (20.00%)	1	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Hepatobiliary disorders
Hyperbilirubinaemia † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	1/5 (20.00%)	1	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1
Immune system disorders
Hypersensitivity † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	1/6 (16.67%)	1	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Infections and infestations
Candidiasis † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	1/4 (25.00%)	1	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Cellulitis † 1	0/6 (0.00%)	0	1/9 (11.11%)	1	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	1/9 (11.11%)	1	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Folliculitis † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	1/5 (20.00%)	1	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Gastroenteritis † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	1/4 (25.00%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0
Gastrointestinal infection † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0
Herpes zoster † 1	0/6 (0.00%)	0	1/9 (11.11%)	1	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Infection † 1	0/6 (0.00%)	0	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	1/6 (16.67%)	2	0/5 (0.00%)	0	0/3 (0.00%)	0	0/4 (0.00%)	0	0/4 (0.00%)	0	0/9 (0.00%)	0	0/4 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0
Laryngitis † 1	1/6 (16.67%)	1	0/9 (0.00%)	0	0/5 (0.00%)	0	0/5 (0.00%)	0	0/6 (0.00%)	0	0/5 (0.00%)