Trial Outcomes & Findings for An Open-label Study of GSK1120212 Compared With Docetaxel in Stage IV KRAS-mutant Non-small Cell Lung Cancer (NCT NCT01362296)

Last Updated: 2014-07-11

Results Overview

PFS is defined as the time from RAN until the earliest date of documented radiological PD or DT due to any cause. PD was assessed by the INV according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. PD is defined as at least a 20% increase in the sum of the diameters (SD) of target lesions with an absolute increase of at least 5 millimeters (mm) or the appearance of at least 1 new lesion, or the worsening of non-target lesions significant enough to require study treatment discontinuation. For participants (PAR) who did not have a documented date of PD or DT, PFS was censored at the date of the last adequate assessment. For PAR who received subsequent anti-cancer therapy prior to the date of documented PD or DT, PFS was censored at the date of the last adequate assessment prior to the initiation of therapy.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

134 participants

Primary outcome timeframe

From randomization (RAN) until the earliest date of documented radiological disease progression (PD) or death (DT) due to any cause (maximum of 10.2 months)

Results posted on

2014-07-11

Participant Flow

Participants who met eligibility criteria at Screening were then randomized to the treatment period. A total of 134 participants were randomized, and 130 participants entered the treatment period.

In the Randomized Phase (RP), participants were treated until disease progression (PD), death, or unacceptable adverse events were experienced. After PD in the RP, participants were given the option of crossing over to the alternative treatment arm in a Cross-over Phase (CP).

Participant milestones

Participant milestones
Measure	GSK1120212 2 mg in RP Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared \[mg/m\^2\]), and continuing in the Cross-over Phase (CP).	Docetaxel 75 mg/m^2 in RP Participants received docetaxel 75 mg per meters squared (m\^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.	GSK1120212 2 mg in CP Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared \[mg/m\^2\]), and continuing in the Cross-over Phase (CP).	Docetaxel 75 mg/m^2 in CP Participants received docetaxel 75 mg per meters squared (m\^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.
Randomized Phase (RP) STARTED	87	43	0	0
Randomized Phase (RP) COMPLETED	0	0	0	0
Randomized Phase (RP) NOT COMPLETED	87	43	0	0
Crossover Phase STARTED	0	0	23	2
Crossover Phase COMPLETED	0	0	0	0
Crossover Phase NOT COMPLETED	0	0	23	2

Reasons for withdrawal

Reasons for withdrawal
Measure	GSK1120212 2 mg in RP Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared \[mg/m\^2\]), and continuing in the Cross-over Phase (CP).	Docetaxel 75 mg/m^2 in RP Participants received docetaxel 75 mg per meters squared (m\^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.	GSK1120212 2 mg in CP Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared \[mg/m\^2\]), and continuing in the Cross-over Phase (CP).	Docetaxel 75 mg/m^2 in CP Participants received docetaxel 75 mg per meters squared (m\^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.
Randomized Phase (RP) PD including Death due to PD	56	28	0	0
Randomized Phase (RP) Physician Decision	1	9	0	0
Randomized Phase (RP) Withdrawal by Subject	2	1	0	0
Randomized Phase (RP) Adverse Event	20	4	0	0
Randomized Phase (RP) Study Closed/Terminated	8	1	0	0
Crossover Phase PD including Death due to PD	0	0	16	1
Crossover Phase Withdrawal by Subject	0	0	2	1
Crossover Phase Adverse Event	0	0	4	0
Crossover Phase Study Closed/Terminated	0	0	1	0

Baseline Characteristics

An Open-label Study of GSK1120212 Compared With Docetaxel in Stage IV KRAS-mutant Non-small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GSK1120212 2 mg in RP n=89 Participants Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared \[mg/m\^2\]), and continuing in the Cross-over Phase (CP).	Docetaxel 75 mg/m^2 in RP n=45 Participants Participants received docetaxel 75 mg per meters squared (m\^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.	Total n=134 Participants Total of all reporting groups
Age, Continuous	61.4 Years STANDARD_DEVIATION 8.97 • n=5 Participants	60.9 Years STANDARD_DEVIATION 10.06 • n=7 Participants	61.2 Years STANDARD_DEVIATION 9.32 • n=5 Participants
Sex: Female, Male Female	43 Participants n=5 Participants	22 Participants n=7 Participants	65 Participants n=5 Participants
Sex: Female, Male Male	46 Participants n=5 Participants	23 Participants n=7 Participants	69 Participants n=5 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	73 Participants n=5 Participants	32 Participants n=7 Participants	105 Participants n=5 Participants
Race/Ethnicity, Customized Asian - East Asian Heritage	11 Participants n=5 Participants	9 Participants n=7 Participants	20 Participants n=5 Participants
Race/Ethnicity, Customized White - Arabic/North African Heritage	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized African American/African Heritage	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Asian - South East Asian Heritage	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Missing	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: From randomization (RAN) until the earliest date of documented radiological disease progression (PD) or death (DT) due to any cause (maximum of 10.2 months)

Population: Modified Intent-to-Treat (MITT) Population: all randomized participants with KRAS mutation-positive non-small cell lung cancer (NSCLC), whether or not treatment was administered

Outcome measures

Outcome measures
Measure	GSK1120212 2 mg in RP n=86 Participants Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared \[mg/m\^2\]), and continuing in the Cross-over Phase (CP).	Docetaxel 75 mg/m^2 in RP n=43 Participants Participants received docetaxel 75 mg per meters squared (m\^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.
Progression-Free Survival (PFS) as Assessed by the Investigator (INV)	11.7 Weeks Interval 7.0 to 12.4	11.4 Weeks Interval 6.1 to 18.3

SECONDARY outcome

Timeframe: Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Randomized Phase (up to Study Week 40)

Population: Safety Population: all participants (KRAS, BRAF, NRAS, and MEK1 mutation positive) that received at least one dose of study treatment, based on the actual treatment received if this differed from that to which the participant was randomized. Only participants with data available at the specified time points were analyzed.

Clinical chemistry parameters were summarized according to National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade, version 4.0. Grade (G) 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to any G, G3, or G4 occurred. Clinical chemistry parameters included: albumin, alkaline phosphatase (ALKP), alanine amino transferase (ALT), aspartate amino transferase (AST), total bilirubin, calcium (hypercalcemia), calcium (hypocalcemia), creatine kinase, creatinine, glucose (hyperglycemia), glucose (hypoglycemia), potassium (hyperkalemia), potassium (hypokalemia), sodium (hypernatremia), and sodium (hyponatremia). Worst-case on-therapy changes from Baseline were summarized. Worst-case on-therapy was defined using the on-therapy window and changes were indentified using both scheduled and unscheduled assessments.

Outcome measures

Outcome measures
Measure	GSK1120212 2 mg in RP n=87 Participants Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared \[mg/m\^2\]), and continuing in the Cross-over Phase (CP).	Docetaxel 75 mg/m^2 in RP n=43 Participants Participants received docetaxel 75 mg per meters squared (m\^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase Albumin, Increase to any G (IAG), n=86, 43	57 Participants	21 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase Albumin, Increase to G4, n=86, 43	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase ALT, IAG, n=87, 43	32 Participants	7 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase ALT, Increase to G4, n=87, 43	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase AST, Increase to G4, n=86, 43	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase Calcium (hypercalcemia), Increase to G3, n=87, 43	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase Calcium (hypocalcemia), Increase to G3, n=87, 43	0 Participants	1 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase Creatinine, Increase to G4, n=87, 43	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase Glucose (hyperglycemia), Increase to G3, n=87, 43	5 Participants	2 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase Glucose (hypoglycemia), IAG, n=87, 43	4 Participants	4 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase Potassium (hyperkalemia), Increase to G4, n=86, 43	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase Sodium (hypernatremia), IAG, n=87, 43	12 Participants	2 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase Sodium (hypernatremia), Increase to G4, n=87, 43	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase Sodium (hyponatremia), Increase to G3, n=87, 43	2 Participants	1 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase Sodium (hyponatremia), Increase to G4, n=87, 43	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase Albumin, Increase to G3, n=86, 43	4 Participants	1 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase ALKP, IAG, n=85, 43	26 Participants	3 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase ALKP, Increase to G3, n =85, 43	2 Participants	1 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase ALKP, Increase to G4, n=85, 43	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase ALT, Increase to G3, n=87, 43	3 Participants	1 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase AST, IAG, n=86, 43	55 Participants	11 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase AST, Increase to G3, n=86, 43	1 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase Total bilirubin, IAG, n=85, 42	3 Participants	3 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase Total bilirubin, Increase to G3, n=85, 42	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase Total bilirubin, Increase to G4, n=85, 42	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase Calcium (hypercalcemia), IAG, n =87, 43	9 Participants	3 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase Calcium (hypercalcemia), Increase to G4, n=87, 43	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase Calcium (hypocalcemia), IAG, n=87, 43	4 Participants	1 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase Calcium (hypocalcemia), Increase to G4, n=87, 43	1 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase Creatine kinase, IAG, n=1, 0	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase Creatine kinase, Increase to G3, n=1, 0	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase Creatine kinase, Increase to G4, n=1, 0	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase Creatinine, IAG, n=87, 43	12 Participants	6 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase Creatinine, Increase to G3, n=87, 43	3 Participants	1 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase Glucose (hyperglycemia), IAG, n=87, 43	47 Participants	24 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase Glucose (hyperglycemia), Increase to G4, n=87, 43	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase Glucose (hypoglycemia), Increase to G3, n=87, 43	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase Glucose (hypoglycemia), Increase to G4, n=87, 43	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase Potassium (hyperkalemia), IAG, n=86,	9 Participants	4 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase Potassium (hyperkalemia), Increase to G3, n=86, 43	1 Participants	1 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase Potassium (hypokalemia), IAG, n=86, 43	8 Participants	2 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase Potassium (hypokalemia), Increase to G3, n=86, 43	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase Potassium (hypokalemia), Increase to G4, n=86, 43	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase Sodium (hypernatremia), Increase to G3, n=87, 43	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase Sodium (hyponatremia), IAG, n=87, 43	16 Participants	5 Participants

SECONDARY outcome

Timeframe: Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Crossover Phase (up to Study Week 19)

Population: Crossover Population: all participants who, at the point of disease progression during the Randomized Phase, elected to enter the crossover portion of the study. Only participants with data available at the specified time points were analyzed.

Clinical chemistry parameters were summarized according to NCI CTCAE grade, version 4.0. Grade (G) 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to any grade, Grade 3, or Grade 4 occurred. Clinical chemistry parameters included: albumin, alkaline phosphatase (ALKP), alanine amino transferase (ALT), aspartate amino transferase (AST), total bilirubin, calcium (hypercalcemia), calcium (hypocalcemia), creatine kinase, creatinine, glucose (hyperglycemia), glucose (hypoglycemia), potassium (hyperkalemia), potassium (hypokalemia), sodium (hypernatremia), and sodium (hyponatremia). Worst-case on-therapy changes from Baseline were summarized. Worst-case on-therapy was defined using the on-therapy window and changes were indentified using both scheduled and unscheduled assessments.

Outcome measures

Outcome measures
Measure	GSK1120212 2 mg in RP n=23 Participants Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared \[mg/m\^2\]), and continuing in the Cross-over Phase (CP).	Docetaxel 75 mg/m^2 in RP n=1 Participants Participants received docetaxel 75 mg per meters squared (m\^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase Albumin, Increase to any G (IAG), n=23, 1	15 Participants	1 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase ALKP, IAG, n=23, 1	10 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase ALKP, Increase to G4, n=23, 1	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase ALT, Increase to G3, n=23, 1	1 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase ALT, Increase to G4, n=23, 1	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase AST, Increase to G3, n=23, 1	1 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase Total bilirubin, IAG, n=22, 1	1 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase Calcium (hypercalcemia), Increase to G4, n=23, 1	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase Calcium (hypocalcemia), Increase to G3, n=23, 1	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase Calcium (hypocalcemia), Increase to G4, n=23, 1	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase Creatine kinase, IAG, n=1, 0	1 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase Creatine kinase, Increase to G3, n=1, 0	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase Creatine kinase, Increase to G4, n=1, 0	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase Creatinine, IAG, n=23, 1	3 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase Creatinine, Increase to G4, n=23, 1	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase Glucose (hyperglycemia), Increase to G3, n=23, 1	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase Glucose (hypoglycemia), IAG, n=23, 1	1 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase Potassium (hyperkalemia), IAG, n=23, 1	3 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase Potassium (hyperkalemia), Increase to G3, n=23, 1	1 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase Potassium (hyperkalemia), Increase to G4, n=23, 1	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase Potassium (hypokalemia), IAG, n=23, 1	1 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase Potassium (hypokalemia), Increase to G3, n=23, 1	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase Potassium (hypokalemia), Increase to G4, n=23, 1	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase Sodium (hypernatremia), IAG, n=23, 1	1 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase Sodium (hypernatremia), Increase to G3, n=23, 1	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase Sodium (hypernatremia), Increase to G4, n=23, 1	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase Sodium (hyponatremia), IAG, n=23, 1	3 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase Sodium (hyponatremia), Increase to G3, n=23, 1	2 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase Sodium (hyponatremia), Increase to G4, n=23, 1	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase Albumin, Increase to G3, n=23, 1	4 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase Albumin, Increase to G4, n=23, 1	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase ALKP, Increase to G3, n =23, 1	1 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase ALT, IAG, n=23, 1	7 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase AST, IAG, n=23, 1	9 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase AST, Increase to G4, n=23, 1	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase Total bilirubin, Increase to G3, n=22, 1	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase Total bilirubin, Increase to G4, n=22, 1	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase Calcium (hypercalcemia), IAG, n =23, 1	1 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase Calcium (hypercalcemia), Increase to G3, n=23, 1	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase Calcium (hypocalcemia), IAG, n=23, 1	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase Creatinine, Increase to G3, n=23, 1	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase Glucose (hyperglycemia), IAG, n=23, 1	10 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase Glucose (hyperglycemia), Increase to G4, n=23, 1	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase Glucose (hypoglycemia), Increase to G3, n=23, 1	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase Glucose (hypoglycemia), Increase to G4, n=23, 1	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Randomized Phase (up to Study Week 40)

Population: Safety Population. Only participants with data available at the specified time points were analyzed.

Hematology parameters were summarized according to NCI CTCAE grade, version 4.0. Grade (G) 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to any G (IAG), G3, or G4 occurred. Hematology parameters included: haemoglobin (increased \[inc\]), haemoglobin (anemia), lymphocyte count (ct) (inc), lymphocyte ct (decreased \[dec\]), total absolute neutrophil count (ANC), platelet ct, and white blood cell count (WBC). Worst-case on-therapy changes from Baseline were summarized. Worst-case on-therapy was defined using the on-therapy window and changes were indentified using both scheduled and unscheduled assessments.

Outcome measures

Outcome measures
Measure	GSK1120212 2 mg in RP n=87 Participants Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared \[mg/m\^2\]), and continuing in the Cross-over Phase (CP).	Docetaxel 75 mg/m^2 in RP n=43 Participants Participants received docetaxel 75 mg per meters squared (m\^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Randomized Phase Haemoglobin (inc), IAG, n=87, 43	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Randomized Phase Haemoglobin (inc), Increase to G3, n=87, 43	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Randomized Phase Haemoglobin (inc), Increase to G4, n=87, 43	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Randomized Phase Haemoglobin (anemia), IAG, n=86, 43	34 Participants	27 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Randomized Phase Haemoglobin (anemia), Increase to G3, n=86, 43	8 Participants	3 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Randomized Phase Haemoglobin (anemia), Increase to G4, n=86, 43	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Randomized Phase Lymphocyte ct (inc), IAG, n=86, 43	9 Participants	2 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Randomized Phase Lymphocyte ct (inc), Increase to G3, n=86, 43	1 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Randomized Phase Lymphocyte ct (inc), Increase to G4, n=86, 43	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Randomized Phase Lymphocyte ct (dec), IAG, n=85, 43	18 Participants	19 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Randomized Phase Lymphocyte ct (dec), Increase to G3, n=85, 43	4 Participants	2 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Randomized Phase Lymphocyte ct (dec), Increase to G4, n=85, 43	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Randomized Phase ANC, IAG, n=86, 43	5 Participants	34 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Randomized Phase ANC, Increase to G3, n=86, 43	0 Participants	13 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Randomized Phase ANC, Increase to G4, n=86, 43	0 Participants	13 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Randomized Phase Platelet ct, IAG, n=87, 43	15 Participants	3 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Randomized Phase Platelet ct, Increase to G3, n=87, 43	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Randomized Phase WBC, Increase to G4, n=87, 43	1 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Randomized Phase Platelet ct, Increase to G4, n=87, 43	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Randomized Phase WBC, IAG, n=87, 43	5 Participants	33 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Randomized Phase WBC, Increase to G3, n=87, 43	0 Participants	17 Participants

SECONDARY outcome

Timeframe: Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Crossover Phase (up to Study Week 19)

Population: Crossover Population. Only participants with data available at the specified time points were analyzed.

Outcome measures

Outcome measures
Measure	GSK1120212 2 mg in RP n=23 Participants Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared \[mg/m\^2\]), and continuing in the Cross-over Phase (CP).	Docetaxel 75 mg/m^2 in RP n=1 Participants Participants received docetaxel 75 mg per meters squared (m\^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Crossover Phase Haemoglobin (inc), IAG, n=23, 1	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Crossover Phase Haemoglobin (inc), Increase to G3, n=23, 1	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Crossover Phase Haemoglobin (inc), Increase to G4, n=23, 1	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Crossover Phase Haemoglobin (anemia), IAG, n=23, 1	12 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Crossover Phase Haemoglobin (anemia), Increase to G3, n=23, 1	2 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Crossover Phase Haemoglobin (anemia), Increase to G4, n=23, 1	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Crossover Phase Lymphocyte ct (inc), IAG, n=23, 1	1 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Crossover Phase Lymphocyte ct (inc), Increase to G3, n=23, 1	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Crossover Phase Lymphocyte ct (inc), Increase to G4, n=23, 1	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Crossover Phase Lymphocyte ct (dec), IAG, n=23, 1	3 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Crossover Phase Lymphocyte ct (dec), Increase to G3, n=23, 1	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Crossover Phase Lymphocyte ct (dec), Increase to G4, n=23, 1	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Crossover Phase ANC, IAG, n=19, 0	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Crossover Phase ANC, Increase to G3, n=19, 0	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Crossover Phase ANC, Increase to G4, n=19, 0	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Crossover Phase Platelet ct, IAG, n=23, 1	4 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Crossover Phase Platelet ct, Increase to G3, n=23, 1	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Crossover Phase Platelet ct, Increase to G4, n=23, 1	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Crossover Phase WBC, IAG, n=23, 1	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Crossover Phase WBC, Increase to G3, n=23, 1	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Crossover Phase WBC, Increase to G4, n=23, 1	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Randomized Phase (up to Study Week 40)

Population: Safety Population. Only participants with data available at the specified time points were analyzed.

Data are presented for only those clinical chemistry parameters for which the following worst-case on-therapy changes from Baseline with respect to the normal range were observed: decrease to low, change to normal (CTN) or no change, or increase to high. Clinical chemistry parameters included: lactate dehydrogenase, total protein, and urea/blood urea nitrogen (BUN). Worst-case on-therapy changes from Baseline were summarized. Worst-case on-therapy was defined using the on-therapy window and changes were indentified using both scheduled and unscheduled assessments. Normal ranges for each parameter may vary depending on the laboratory (central versus local) and the participant (age, gender, etc.).

Outcome measures

Outcome measures
Measure	GSK1120212 2 mg in RP n=87 Participants Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared \[mg/m\^2\]), and continuing in the Cross-over Phase (CP).	Docetaxel 75 mg/m^2 in RP n=43 Participants Participants received docetaxel 75 mg per meters squared (m\^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Clinical Chemistry Parameters: Randomized Phase Lactate dehydrogenase, Decrease to low, n=87, 43	1 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Clinical Chemistry Parameters: Randomized Phase Lactate dehydrogenase, CTN or no change, n=87, 43	40 Participants	23 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Clinical Chemistry Parameters: Randomized Phase Lactate dehydrogenase, Increase to high, n=87, 43	46 Participants	20 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Clinical Chemistry Parameters: Randomized Phase Total Protein, Decrease to low, n=86, 43	31 Participants	12 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Clinical Chemistry Parameters: Randomized Phase Total Protein, CTN or no change, n=86, 43	55 Participants	31 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Clinical Chemistry Parameters: Randomized Phase Total Protein, Increase to high, n=86, 43	1 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Clinical Chemistry Parameters: Randomized Phase Urea/BUN, Decrease to low, n=87, 43	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Clinical Chemistry Parameters: Randomized Phase Urea/BUN, CTN or no change, n=87, 43	62 Participants	34 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Clinical Chemistry Parameters: Randomized Phase Urea/BUN, Increase to high, n=87,43	25 Participants	9 Participants

SECONDARY outcome

Timeframe: Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Crossover Phase (up to Study Week 19)

Population: Crossover Population. Only participants with data available at the specified time points were analyzed.

Outcome measures

Outcome measures
Measure	GSK1120212 2 mg in RP n=23 Participants Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared \[mg/m\^2\]), and continuing in the Cross-over Phase (CP).	Docetaxel 75 mg/m^2 in RP n=1 Participants Participants received docetaxel 75 mg per meters squared (m\^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Clinical Chemistry Parameters: Crossover Phase Lactate dehydrogenase, Decrease to low	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Clinical Chemistry Parameters: Crossover Phase Lactate dehydrogenase, CTN or no change	15 Participants	1 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Clinical Chemistry Parameters: Crossover Phase Lactate dehydrogenase, Increase to high	8 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Clinical Chemistry Parameters: Crossover Phase Total Protein, Decrease to low	15 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Clinical Chemistry Parameters: Crossover Phase Total Protein, CTN or no change	8 Participants	1 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Clinical Chemistry Parameters: Crossover Phase Total Protein, Increase to high	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Clinical Chemistry Parameters: Crossover Phase Urea/BUN, Decrease to low	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Clinical Chemistry Parameters: Crossover Phase Urea/BUN, CTN or no change	18 Participants	1 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Clinical Chemistry Parameters: Crossover Phase Urea/BUN, Increase to high	5 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Randomized Phase (up to Study Week 40)

Population: Safety Population. Only participants with data available at the specified time points were analyzed.

Data are presented for only those hematology parameters for which the following worst-case on-therapy changes from Baseline with respect to the normal range were observed: decrease to low, change to normal (CTN) or no change, or increase to high. Hematology parameters included: atypical lymphs, atypical lymphs (percentage \[%\]), basophils, eosinophils, metamyelocytes, monocytes, myelocytes, neutrophil bands (%). Worst-case on-therapy changes from Baseline were summarized. Worst-case on-therapy was defined using the on-therapy window and changes were indentified using both scheduled and unscheduled assessments. Normal ranges for each parameter may vary depending on the laboratory (central versus local) and the participant (age, gender, etc.).

Outcome measures

Outcome measures
Measure	GSK1120212 2 mg in RP n=86 Participants Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared \[mg/m\^2\]), and continuing in the Cross-over Phase (CP).	Docetaxel 75 mg/m^2 in RP n=43 Participants Participants received docetaxel 75 mg per meters squared (m\^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Randomized Phase Atypical lymphs (%), Increase to high, n=0, 3	0 Participants	3 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Randomized Phase Basophils, CTN or no change, n=86, 43	82 Participants	41 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Randomized Phase Myelocytes, Decrease to low, n=1, 9	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Randomized Phase Atypical lymphs, Decrease to low, n=0, 3	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Randomized Phase Atypical lymphs, CTN or no change, n=0, 3	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Randomized Phase Atypical lymphs, Increase to high, n=0, 3	0 Participants	3 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Randomized Phase Atypical lymphs (%), Decrease to low, n =0, 3	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Randomized Phase Atypical lymphs (%), CTN or no change, n=0, 3	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Randomized Phase Basophils, Decrease to low, n=86, 43	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Randomized Phase Basophils, Increase to high, n=86,43	4 Participants	2 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Randomized Phase Eosinophils, Decrease to low, n=86, 43	1 Participants	1 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Randomized Phase Eosinophils, CTN or no change, n=86, 43	77 Participants	42 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Randomized Phase Eosinophils, Increase to high, n=86, 43	9 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Randomized Phase Metamyelocytes, Decrease to low, n=1, 7	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Randomized Phase Metamyelocytes, CTN or no change, n=1, 7	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Randomized Phase Metamyelocytes, Increase to high, n=1, 7	1 Participants	7 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Randomized Phase Monocytes, Decrease to low, n=86, 43	3 Participants	20 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Randomized Phase Monocytes, CTN or no change, n=86, 43	78 Participants	18 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Randomized Phase Monocytes, Increase to high, n=86, 43	5 Participants	9 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Randomized Phase Myelocytes, CTN or no change, n=1, 9	0 Participants	1 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Randomized Phase Myelocytes, Increase to high, n=1, 9	1 Participants	8 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Randomized Phase Neutrophil Bands (%), Decrease to low, n=1, 4	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Randomized Phase Neutrophil Bands (%), CTN or no change, n=1, 4	1 Participants	3 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Randomized Phase Neutrophil Bands (%), Increase to high, n=1, 4	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Crossover Phase (up to Study Week 19)

Population: Crossover Population. Only participants with data available at the specified time points were analyzed.

Data are presented for only those hematology parameters for which the following worst-case on-therapy changes from Baseline with respect to the normal range were observed: decrease to low, change to normal (CTN) or no change, or increase to high. Hematology parameters included: atypical lymphs, atypical lymphs (percentage \[%\]), basophils, eosinophils, metamyelocytes, monocytes, and myelocytes. Worst-case on-therapy changes from Baseline were summarized. Worst-case on-therapy was defined using the on-therapy window and changes were indentified using both scheduled and unscheduled assessments. Normal ranges for each parameter may vary depending on the laboratory (central versus local) and the participant (age, gender, etc.).

Outcome measures

Outcome measures
Measure	GSK1120212 2 mg in RP n=23 Participants Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared \[mg/m\^2\]), and continuing in the Cross-over Phase (CP).	Docetaxel 75 mg/m^2 in RP n=1 Participants Participants received docetaxel 75 mg per meters squared (m\^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Crossover Phase Atypical lymphs, CTN or no change, n=3, 1	1 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Crossover Phase Basophils, CTN or no change, n=23, 1	23 Participants	1 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Crossover Phase Atypical lymphs (%), CTN or no change, n=3, 1	1 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Crossover Phase Atypical lymphs (%), Increase to high, n=3, 1	2 Participants	1 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Crossover Phase Basophils, Decrease to low, n=23, 1	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Crossover Phase Atypical lymphs, Decrease to low, n=3, 1	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Crossover Phase Atypical lymphs, Increase to high, n=3, 1	2 Participants	1 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Crossover Phase Basophils, Increase to high, n=23, 1	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Crossover Phase Eosinophils, Decrease to low, n=23, 1	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Crossover Phase Eosinophils, CTN or no change, n=23, 1	23 Participants	1 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Crossover Phase Atypical lymphs (%), Decrease to low, n=3, 1	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Crossover Phase Eosinophils, Increase to high, n=23, 1	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Crossover Phase Metamyelocytes, Decrease to low, n=1, 1	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Crossover Phase Metamyelocytes, CTN or no change, n=1, 1	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Crossover Phase Metamyelocytes, Increase to high, n=1, 1	1 Participants	1 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Crossover Phase Monocytes, Decrease to low, n=23, 1	1 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Crossover Phase Monocytes, CTN or no change, n=23, 1	20 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Crossover Phase Monocytes, Increase to high, n=23, 1	2 Participants	1 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Crossover Phase Myelocytes, Decrease to low, n=3, 1	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Crossover Phase Myelocytes, CTN or no change, n=3, 1	0 Participants	0 Participants
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Crossover Phase Myelocytes, Increase to high, n=3, 1	3 Participants	1 Participants

SECONDARY outcome

Timeframe: From randomization until 30 days following discontinuation of study treatment regardless of initiation of a new cancer therapy or transfer to hospice (maximum of 19 months)

Population: Safety Population

An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. Medical or scientific judgment should have been exercised in deciding whether reporting was appropriate in other situations. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs.

Outcome measures

Outcome measures
Measure	GSK1120212 2 mg in RP n=87 Participants Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared \[mg/m\^2\]), and continuing in the Cross-over Phase (CP).	Docetaxel 75 mg/m^2 in RP n=43 Participants Participants received docetaxel 75 mg per meters squared (m\^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.
Number of Participants With Any Serious Adverse Event (SAE) or Non-serious Adverse Event (AE): Randomized Phase Any AE	87 Participants	43 Participants
Number of Participants With Any Serious Adverse Event (SAE) or Non-serious Adverse Event (AE): Randomized Phase Any SAE	32 Participants	9 Participants

SECONDARY outcome

Timeframe: From the date of the first dose of study treatment in the Crossover Phase until 30 days following discontinuation of study treatment regardless of initiation of a new cancer therapy or transfer to hospice (maximum of 12 months)

Population: Crossover Population

Outcome measures

Outcome measures
Measure	GSK1120212 2 mg in RP n=23 Participants Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared \[mg/m\^2\]), and continuing in the Cross-over Phase (CP).	Docetaxel 75 mg/m^2 in RP n=2 Participants Participants received docetaxel 75 mg per meters squared (m\^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.
Number of Participants With Any SAE or Non-serious AE: Crossover Phase Any AE	22 Participants	2 Participants
Number of Participants With Any SAE or Non-serious AE: Crossover Phase Any SAE	12 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Randomized Phase (up to Study Week 40)

Population: Safety Population. Only participants with data available at the specified time points were analyzed.

Systolic and diastolic blood pressure were measured at the following scheduled time points: Baseline; Days 1, 8, and 15 of Cycle 1 (Study Week 1); and Day 1 of every cycle thereafter until treatment discontinuation. The worst-case on-therapy was determined using both scheduled and unscheduled assessments during the on-therapy period. Change from Baseline was calculated as the value at post-Baseline time point minus the value at Baseline.

Outcome measures

Outcome measures
Measure	GSK1120212 2 mg in RP n=87 Participants Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared \[mg/m\^2\]), and continuing in the Cross-over Phase (CP).	Docetaxel 75 mg/m^2 in RP n=43 Participants Participants received docetaxel 75 mg per meters squared (m\^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP): Randomized Phase SBP, Worst-case on-therapy	13.5 millimeters of mercury (mmHg) Standard Deviation 16.63	3.1 millimeters of mercury (mmHg) Standard Deviation 13.71
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP): Randomized Phase DBP, Worst-case on-therapy	10.7 millimeters of mercury (mmHg) Standard Deviation 9.95	2.5 millimeters of mercury (mmHg) Standard Deviation 7.34

SECONDARY outcome

Timeframe: Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Crossover Phase (up to Study Week 19)

Population: Crossover Population. Only participants with data available at the specified time points were analyzed.

Systolic and diastolic blood pressure were measured at the following scheduled time points: Baseline; Days 1, 8, and 15 of Cycle 1 (Study Week 1); and Day 1 of every cycle therafter until treatment discontinuation. The worst-case on-therapy was determined using both scheduled and unscheduled assessments during the on-therapy period. Change from Baseline was calculated as the value at post-Baseline time point minus the value at Baseline.

Outcome measures

Outcome measures
Measure	GSK1120212 2 mg in RP n=23 Participants Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared \[mg/m\^2\]), and continuing in the Cross-over Phase (CP).	Docetaxel 75 mg/m^2 in RP n=1 Participants Participants received docetaxel 75 mg per meters squared (m\^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.
Change From Baseline in SBP and DBP: Crossover Phase SBP, Worst-case on-therapy	8.7 mmHg Standard Deviation 15.95	-15.0 mmHg Standard Deviation NA Only one participant was analyzed in this treatment arm at this time point; therefore the standard deviation cannot be calculated.
Change From Baseline in SBP and DBP: Crossover Phase DBP, Worst-case on-therapy	8.3 mmHg Standard Deviation 12.28	-12.0 mmHg Standard Deviation NA Only one participant was analyzed in this treatment arm at this time point; therefore the standard deviation cannot be calculated.

SECONDARY outcome

Timeframe: Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Randomized Phase (up to Study Week 40)

Population: Safety Population. Only participants with data available at the specified time points were analyzed.

Heart rate was measured at the following scheduled time points: Baseline; Days 1, 8, and 15 of Cycle 1 (Study Week 1); and Day 1 of every cycle therafter until treatment discontinuation.The worst-case on-therapy was determined using both scheduled and unscheduled assessments during the on-therapy period. Change from Baseline was calculated as the value at post-Baseline time point minus the value at Baseline.

Outcome measures

Outcome measures
Measure	GSK1120212 2 mg in RP n=87 Participants Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared \[mg/m\^2\]), and continuing in the Cross-over Phase (CP).	Docetaxel 75 mg/m^2 in RP n=43 Participants Participants received docetaxel 75 mg per meters squared (m\^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.
Change From Baseline in Heart Rate: Randomized Phase	10.4 Beats per minute Standard Deviation 14.23	13.2 Beats per minute Standard Deviation 9.31

SECONDARY outcome

Timeframe: Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Crossover Phase (up to Study Week 19)

Population: Crossover Population. Only participants with data available at the specified time points were analyzed.

Outcome measures

Outcome measures
Measure	GSK1120212 2 mg in RP n=23 Participants Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared \[mg/m\^2\]), and continuing in the Cross-over Phase (CP).	Docetaxel 75 mg/m^2 in RP n=1 Participants Participants received docetaxel 75 mg per meters squared (m\^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.
Change From Baseline in Heart Rate: Crossover Phase	8.5 Beats per minute Standard Deviation 11.46	5.0 Beats per minute Standard Deviation NA Only one participant was analyzed in this treatment arm at this time point; therefore the standard deviation cannot be calculated.

SECONDARY outcome

Timeframe: From randomization until the first documented evidence of a CR or PR (maximum of 10.2 months)

Population: MITT Population

Response was assessed by the investigator according to RECIST, version 1.1, using confirmed and unconfirmed responses. Responders were defined as participants achieving either a CR (disappearance of all target and non-target lesions; any pathological lymph nodes must be \<10 millimeters \[mm\] in the short axis; without the appearance of new lesions) or PR (at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters \[e.g., percent change from Baseline\]). Participants with unknown or missing response were treated as non-responders.

Outcome measures

Outcome measures
Measure	GSK1120212 2 mg in RP n=86 Participants Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared \[mg/m\^2\]), and continuing in the Cross-over Phase (CP).	Docetaxel 75 mg/m^2 in RP n=43 Participants Participants received docetaxel 75 mg per meters squared (m\^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.
Number of Participants With a Best Response of Either a Complete Response (CR) or Partial Response (PR) as Assessed by the Investigator: Randomized Phase CR	0 Participants	0 Participants
Number of Participants With a Best Response of Either a Complete Response (CR) or Partial Response (PR) as Assessed by the Investigator: Randomized Phase PR	10 Participants	5 Participants

SECONDARY outcome

Timeframe: From the date of the first dose of study treatment in the Crossover Phase until the first documented evidence of a CR or PR (maximum of 4 months)

Population: Crossover Population

Outcome measures

Outcome measures
Measure	GSK1120212 2 mg in RP n=23 Participants Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared \[mg/m\^2\]), and continuing in the Cross-over Phase (CP).	Docetaxel 75 mg/m^2 in RP n=2 Participants Participants received docetaxel 75 mg per meters squared (m\^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.
Number of Participants With a Best Response of Either a CR or PR as Assessed by the Investigator: Crossover Phase CR	0 Participants	0 Participants
Number of Participants With a Best Response of Either a CR or PR as Assessed by the Investigator: Crossover Phase PR	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Time from the first documented evidence of CR or PR until the earliest date of documented radiological progression or death due to any cause (maximum of 10.2 months)

Population: MITT Population. Only participants who achieved a CR or PR were analyzed for duration of response.

DOR was assessed by the investigator for participants with CR (disappearance of all target and non-target lesions; any pathological lymph nodes must be \<10 mm in the short axis; without the appearance of new lesions) or PR (at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters \[e.g., percent change from Baseline\]). DOR is defined as the time from the first documented evidence of CR or PR until the earliest date of documented radiological progression or death due to any cause. PD is defined as at least a 20% increase in the sum of the diameters (SD) of target lesions with an absolute increase of at least 5 millimeters (mm) or the appearance of at least 1 new lesion, or the worsening of non-target lesions significant enough to require study treatment discontinuation.

Outcome measures

Outcome measures
Measure	GSK1120212 2 mg in RP n=10 Participants Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared \[mg/m\^2\]), and continuing in the Cross-over Phase (CP).	Docetaxel 75 mg/m^2 in RP n=5 Participants Participants received docetaxel 75 mg per meters squared (m\^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.
Duration of Response (DOR) as Assessed by the Investigator: Randomized Phase	6.7 Weeks Interval 2.7 to There were a limited number of participants with a CR or PR who later progressed or died; therefore, the upper limit (UL) of the CI could not be estimated.	12.4 Weeks Interval 7.1 to 17.3

SECONDARY outcome

Timeframe: Time interval between the date of randomization and the date of death due to any cause (maximum of 22 months)

Population: MITT Population

OS is defined as the interval of time between the date of randomization and the date of death due to any cause. For participants who did not die, OS was censored at the date of last contact.

Outcome measures

Outcome measures
Measure	GSK1120212 2 mg in RP n=86 Participants Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared \[mg/m\^2\]), and continuing in the Cross-over Phase (CP).	Docetaxel 75 mg/m^2 in RP n=43 Participants Participants received docetaxel 75 mg per meters squared (m\^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.
Overall Survival (OS)	8.1 Months Interval 6.8 to 10.0	9.9 Months Interval 5.0 to Statistics for the median is missing because an insufficient number of participants reached the milestone, making calculation of this statistic inappropriate or impossible.

SECONDARY outcome

Timeframe: Day 15 of Cycle 1: pre-dose; 0.5-2 hours, 2-4 hours, and 4-8 hours post-dose; Day 1 of Cycle 2, Cycle 3 and Cycle 4: pre-dose

Population: PK Population. Only participants with data available at the specified time points were analyzed.

Blood samples for PK analysis of GSK1120212 were collected at the following time points: Cycle 1 (Study Day 15), Cycle 2 (Study Day 22), Cycle 3 (Study Day 43), and Cycle 4 (Study Day 64). Post-dose PK samples collected on Day 15 of Cycle 1 occurred at least 1 hour apart. Participants were instructed to withhold the dose of GSK1120212 until after blood for PK samples had been drawn. Pre-dose samples were taken 15 minutes or less prior to taking the next dose (i.e., trough).

Outcome measures

Outcome measures
Measure	GSK1120212 2 mg in RP n=80 Participants Participants received GSK1120212 2 milligrams (mg) orally once daily continuously in the Randomized Phase (RP). Participants continued treatment until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (docetaxel 75 milligrams per meters squared \[mg/m\^2\]), and continuing in the Cross-over Phase (CP).	Docetaxel 75 mg/m^2 in RP Participants received docetaxel 75 mg per meters squared (m\^2) intravenously (IV) every 3 weeks in the RP. Participants continued treatment on a 21-day cycle until disease progression, death, or unacceptable adverse events were experienced. Participants who experienced disease progression in the RP were given the option of crossing over to the alternative treatment arm (GSK1120212 2 mg), and continuing in the CP.
GSK1120212 Plasma Pharmacokinetic (PK) Concentration Cycle 1, Day 15, pre-dose, n=80	16.1 Nanograms (ng)/milliliter (mL) Standard Deviation 5.31	—
GSK1120212 Plasma Pharmacokinetic (PK) Concentration Cycle 1, Day 15, 0.5-2 hours post-dose, n=78	21.5 Nanograms (ng)/milliliter (mL) Standard Deviation 8.59	—
GSK1120212 Plasma Pharmacokinetic (PK) Concentration Cycle 1, Day 15, 2-4 hours post-dose, n=77	29.7 Nanograms (ng)/milliliter (mL) Standard Deviation 22.9	—
GSK1120212 Plasma Pharmacokinetic (PK) Concentration Cycle 1, Day 15, 4-8 hours post-dose, n=78	24.8 Nanograms (ng)/milliliter (mL) Standard Deviation 7.80	—
GSK1120212 Plasma Pharmacokinetic (PK) Concentration Cycle 2, Day 1, pre-dose, n=75	16.7 Nanograms (ng)/milliliter (mL) Standard Deviation 6.95	—
GSK1120212 Plasma Pharmacokinetic (PK) Concentration Cycle 3, Day 1, pre-dose, n=60	12.9 Nanograms (ng)/milliliter (mL) Standard Deviation 7.19	—
GSK1120212 Plasma Pharmacokinetic (PK) Concentration Cycle 4, Day 1, pre-dose, n=38	13.9 Nanograms (ng)/milliliter (mL) Standard Deviation 6.49	—

Adverse Events

GSK1120212 2 mg in RP

Serious events: 32 serious events

Other events: 87 other events

Deaths: 0 deaths

Docetaxel 75 mg/m^2 in RP

Serious events: 9 serious events

Other events: 43 other events

Deaths: 0 deaths

GSK1120212 2 mg in CP

Serious events: 12 serious events

Other events: 20 other events

Deaths: 0 deaths

Docetaxel 75 mg/m^2 in CP

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER