An AE is 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 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; important medical events that may require medical or surgical intervention to prevent one of the outcomes mentioned; events of possible study treatment-induced liver injury with hyperbilirubinemia; and left ventricular ejection fraction (LVEF) meeting stopping criteria. AEs were collected in All Treated Population which comprised of all participants who received at least one dose of GSK2849330. Treatment groups with same dose and administration frequency were combined as pre-specified in reporting and analysis plan.

All Treated Population

An event was considered a DLT if it occured within the first 4 weeks (28 days) of treatment, and met one of the following criteria unless it could be established that the event was unrelated to treatment: Grade 3 or greater non-hematologic toxicity; Grade 4 neutropenia lasting >5 days; Febrile neutropenia, of any grade or duration; Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia associated with bleeding; Alanine aminotransferase (ALT) >3 times upper limit of normal (ULN) with bilirubin >2 times ULN; Any Grade 2 or greater toxicity that in the judgment of the investigator and GlaxoSmithKline (GSK) Medical Monitor, would be considered dose-limiting; Grade 3 or greater decrease in LVEF. Treatment groups with same dose and administration frequency were combined as pre-specified in reporting and analysis plan.

All Treated Population

Blood samples were collected for the analysis of following clinical chemistry parameters: albumin, alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (Total bil), calcium, creatinine, gamma glutamyl transferase (GGT), glucose, potassium, magnesium, sodium, phosphorus, uric acid. Laboratory parameters were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences; Grade 5: death related to AE. Baseline is the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date. Change from Baseline was calculated as visit value minus Baseline value. Data for worst-case post Baseline is presented. Treatment groups with same dose and administration frequency were combined as pre-specified in reporting and analysis plan.

All Treated Population. Only those participants with data available at specified time points were analyzed (represented by n=X in category titles).

Blood samples were collected for the analysis of following clinical chemistry parameters: direct bilirubin (D.Bil.), cancer antigen (CA)-125, CA-15.3, CA19-9, chloride, carbon dioxide (CO2)/bicarbonate (HCO3), luteinizing hormone (LH), total protein and urea or blood urea nitrogen (BUN). Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date. Change from Baseline was calculated as visit value minus Baseline value. A laboratory value that is outside the reference range was considered either high abnormal (value above the upper limit of the reference range) or low abnormal (value below the lower limit of the reference range). Number of participants with change from Baseline in clinical chemistry data at worst-case post Baseline is presented. Treatment groups with same dose and administration frequency were combined as pre-specified in reporting and analysis plan.

All Treated Population. Only those participants with data available at specified time points were analyzed (represented by n=X in category titles).

Blood samples were collected for the analysis of following hematology parameters: hemoglobin, lymphocytes, total neutrophils, platelet count, and white blood cell (WBC). The laboratory parameters were graded according to NCI-CTCAE version 4.0. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences; Grade 5: death related to AE. Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date. Change from Baseline was calculated as visit value minus Baseline value. Number of participants with any grade increase, increase to Grade 3 and increase to Grade 4 in hematology data at worst-case post Baseline is presented. Treatment groups with same dose and administration frequency were combined as pre-specified in reporting and analysis plan.

All Treated Population

Blood samples were collected for the analysis of following hematology parameters: basophils, eosinophils, hematocrit, mean corpuscle hemoglobin concentration (MCHC), mean corpuscle hemoglobin (MCH), mean corpuscle volume (MCV), monocytes, red blood cell count (RBC) and reticulocytes. A laboratory value that was outside the reference range was considered either high abnormal (value above the upper limit of the reference range) or low abnormal (value below the lower limit of the reference range). Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date. Change from Baseline was calculated as value at visit minus Baseline value. Number of participants with change from Baseline in hematology data at worst-case post Baseline is presented. Treatment groups with same dose and administration frequency were combined as pre-specified in reporting and analysis plan.

All Treated Population

Urine samples were collected for the analysis of urine potential of hydrogen (pH) and urine specific gravity. A laboratory value that was outside the reference range was considered either high abnormal (value above the upper limit of the reference range) or low abnormal (value below the lower limit of the reference range). Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date. Change from Baseline was calculated as visit value minus Baseline value. The data for worst-case post Baseline is presented. Treatment groups with same dose and administration frequency were combined as pre-specified in reporting and analysis plan.

All Treated Population. Only those participants with data available at specified time points were analyzed (represented by n=X in category titles).

Vital sign measurements included systolic blood pressure (SBP), diastolic blood pressure (DBP), temperature (Temp) and heart rate (HR). Vital signs were graded according to NCI-CTCAE version 4.0. The following criteria was used to flag vital signs of potential clinical importance: change from Baseline in HR (decrease to <60 beats per minute and increase to >100 beats per minute); increase in SBP from Baseline (>=120 to <140 millimeters of mercury [mmHg] Grade 1; >=140 to <160 mmHg [Grade 2]; >=160 [Grade 3]); increase in DBP from Baseline (>=80 to <90 [Grade 1]; >=90 to <100 [Grade 2]; >=100 mmHg [Grade 3]) and change in temperature from Baseline (increase to >=38 or decrease to <=35 degree Centigrade). Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Change from Baseline was calculated as visit value minus Baseline value. The data for worst-case post Baseline is presented.

All Treated Population

A 12-lead ECG was measured using an automated ECG machine after at least 5 minutes of rest for the participant in a semi-recumbent or supine position. Number of participants with abnormal ECG findings at any time post-Baseline is presented. Treatment groups with same dose and administration frequency were combined as pre-specified in reporting and analysis plan.

All Treated Population

The first occurrence of the maximum observed plasma concentration determined directly from the raw concentration-time data is defined as Cmax. Blood samples were collected at indicated time points. The analysis was performed on pharmacokinetic (PK) parameter population which comprised of all participants from the PK concentration population (participants who received at least one dose of GSK2849330 and for whom at least one post-dose PK sample was obtained and analyzed) for whom valid and valuable PK parameters were derived.

PK Parameter Population

PK parameters for Part 2 were not analyzed due to sparse sampling. The protocol was written in a flexible way to either pursue or not pursue additional analyses in Part 2.

PK Parameter Population. PK parameters for Part 2 were not analyzed due to sparse sampling.

The time at which Cmax is observed was determined directly from the raw concentration-time data is defined as Tmax. Blood samples were collected at indicated time points for evaluation of pharmacokinetic parameters.

PK Parameter Population

PK parameters for Part 2 were not analyzed due to sparse sampling. The protocol was written in a flexible way to either pursue or not pursue additional analyses in Part 2.

PK Parameter Population. PK parameters for Part 2 were not analyzed due to sparse sampling.

The AUC to a fixed nominal time AUC(0-168) and AUC(0-336) were calculated using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. Blood samples were collected at indicated time points for determination of PK parameters.

PK Parameter Population. Only those participants with data available at specified time points were analyzed (indicated by n=X in category titles).

PK parameters for Part 2 were not analyzed due to sparse sampling. The protocol was written in a flexible way to either pursue or not pursue additional analyses in Part 2.

PK Parameter Population. PK parameters for Part 2 were not analyzed due to sparse sampling.

Pre-treatment and on-treatment biopsy tissues (tumor and normal skin) were analyzed for markers of HER3 pathway such as HER3 that may indicate a pharmacodynamic (PD) response to GSK2849330. Serum HER3 (soluble HER3) analyses was performed. The analysis was performed on PD population which comprised of all participants who received at least one dose of GSK2849330 and for whom at least one evaluable paired pre-treatment PD sample and on-treatment PD sample were obtained and analyzed. Mean and standard deviation for serum HER3 is presented. Treatment groups with same dose and administration frequency were combined as pre-specified in reporting and analysis plan.

PD Population. Only those participants with data available at specified time points were analyzed (indicated by n=X in category titles).

ORR was determined by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST v 1.1). ORR was calculated as the number of participants with best overall response of complete response (CR) and partial response (PR). CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 millimeter (mm) in the short axis and 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). An estimate to the true response rate for the number of participants analyzed is given. The 95% confidence interval was the exact confidence interval based on binomial proportion for ORR. Treatment groups with same dose and administration frequency were combined as pre-specified in reporting and analysis plan.

All Treated Population

Serum samples were collected for the determination of anti-GSK2849330 antibodies using a validated immunoelectrochemiluminescent (ECL) assay. The assay involved screening, confirmation and titration steps (tiered-testing approach). If serum samples contained anti-GSK2849330 antibodies, they were further analyzed for the specificity of antibodies by a confirmation assay. Confirmed positive samples were titrated to obtain the titers of antibodies. The number of participants who tested positive for anti-GSK2849330 antibody in confirmatory testing on Day 1 and at any time post-Baseline is presented. Treatment groups with same dose and administration frequency were combined as pre-specified in reporting and analysis plan.

All Treated Population. Only those participants with data available at specified time points were analyzed (indicated by n=X in category titles)

Blood samples were collected on Day (D) 1 at pre-dose (pre) and at 1 hour (h) and 6 h post infusion for the analysis of markers to evaluate biological activity of GSK2849330. A pre-dose blood sample was collected on D8, D15 and D29 with additional blood sample collected at progression of disease. CDX241 represent CD45+CD3-CD56+CD16+CD69+CD107+, CDX243=CD45+CD3-CD56+CD16+CD69+CD107-; CDX244=CD45+CD3-CD56+CD16+CD69-CD107+ and CDX245=CD45+CD3-CD56+CD16+CD69-CD107-. For participants in GSK2849330 3 mg/kg weekly arm, two samples (S1 and S2) were collected for D15 analysis. Treatment groups with same dose and administration frequency were combined as pre-specified in reporting and analysis plan.

PD Population. Only those participants with data available at specified time points were analyzed (indicated by n=X in category titles)