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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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:
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
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
Hide 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
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
Hide 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
Hide 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%
1.Primary Outcome
Title Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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%
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
Hide 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%)    
Hide 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
Hide 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%)