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Subject will receive GSK3052230 as 30-minute intravenous (i.v.) infusion once a week (Day 1, Day 8, Day 15) of each 21-day cycle + paclitaxel (constant infusion for 3 hrs) and carboplatin (constant infusion for 30 to 60 minutes) iv on Day 1 of each 21-day cycle. The number of cycles of paclitaxel/carboplatin will be limited to 4 to 6 cycles.

Subject will receive GSK3052230 as 30-minute intravenous (i.v.) infusion once a week (Day 1, Day 8, Day 15) of each 21-day cycle + docetaxel as 1 hour iv infusion on Day 1 of each 21-day cycle. Subjects may continue to receive docetaxel until disease progression or as long as they are considered to derive benefit from treatment.

Subject will receive GSK3052230 as 30 minute iv infusion once a week (Day 1, Day 8, Day 15) of each 21 day cycle + pemetrexed iv infusion over 10 minutes on Day 1 of each 21 day cycle followed 30 minutes later by iv Cisplatin infused over 2 hours

A clear to opalescent, colorless to pale yellow solution for IV infusion once weekly (Day 1, Day 8, Day 15) in each 21-day cycle with unit dose strengths/dose level of 5, 10, 15, and 20 mg/kg supplied in a sterile 25 mL glass vial.

GSK3052230

paclitaxel will be from commercial stock.

paclitaxel

carboplatin will be from commercial stock.

carboplatin

docetaxel

pemetrexed

cisplatin

GSK Clinical Trials

This phase IB trial aims to identify anticancer activity of GSK3052230 in subjects with malignancies with abnormal dependence on FGF pathway signaling. Combination doses of GSK3052230 with standard of care chemotherapy in the first and second line or greater setting of metastatic squamous non-small cell lung cancer (NSCLC) and first line malignant pleural mesothelioma subjects will be studied in the 3+3 dose-escalation design. This will be a multi-arm, multicenter, non-randomized, parallel-group, uncontrolled, open-label Phase IB study designed to evaluate the safety, tolerability and preliminary activity of GSK3052230 in combination with paclitaxel + carboplatin (Arm A), in combination with docetaxel (Arm B), or in combination with pemetrexed + cisplatin (Arm C). Approximately 70 subjects will be enrolled in the study (approximately up to 120 may be enrolled).

Study to Evaluate GSK3052230 in Combination With Paclitaxel and Carboplatin, or Docetaxel or as Single Agent in Subjects With Solid Malignancies and Deregulated Fibroblast Growth Factor (FGF) Pathway Signaling

Multi-arm, Non-randomized, Open-Label Phase IB Study to Evaluate GSK3052230 in Combination With Paclitaxel and Carboplatin, or Docetaxel or as Single Agent in Subjects With Solid Malignancies and Deregulated FGF Pathway Signaling

IPD for this study will be made available via the Clinical Study Data Request site.

An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, protocol-specific events including drug-induced liver injury with hyperbilirubinaemia, any new primary cancers, cardiac toxicity including Left Ventricular Ejection Fraction (LVEF) changes or treatment emergent cardiac valve toxicity and treatment emergent acute anterior uveitis were categorized as SAE. Participants having non-serious AE or SAE were included in the analysis. The All Treated Subjects Population comprised of all participants who received at least one dose of study treatment.

The severity of AEs were graded utilizing National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.3. Grade 1 represents mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 represents moderate; minimal, local or noninvasive intervention indicated. Grade 3 represents severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling. Grade 4 represents life-threatening consequences; urgent intervention indicated. Grade 5 represents death related to AE.

An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. The AEs leading to permanent discontinuation from the study has been reported.

Dose reduction and delays were done due to toxicity, or in the interest of participant's safety per investigator discretion. Requirement for more than 2 dose reductions resulted in permanent discontinuation of chemotherapy. Participants with dose reduction has been reported.

Dose reduction and delays were done due to toxicity, or in the interest of participant's safety per investigator discretion. Requirement for more than 2 dose reductions resulted in permanent discontinuation of chemotherapy. Participants with dose delay has been reported.

The number of participants administered study treatment were summarized according to the duration of therapy. The extent of treatment exposure is calculated as the number of cycles administered. The duration of exposure to study treatment is calculated from first day to last day of treatment plus 1 day. Median and full range (minimum and maximum) has been reported.

DLT is defined as toxicities due to GSK3052230 or due to the combination of GSK3052230 with chemotherapy within Cycle 1 (first 21 days of period on study) that are unlikely to be due to another cause, such as the known effects of cytotoxics chemotherapy alone, disease progression, or accident, and protocol-specified criteria. Clinically significant toxicities that persist or occur beyond Cycle 1 that the investigator and GlaxoSmithKline (GSK) medical monitor consider dose-limiting may also be designated a DLT for the purpose of establishing Maximum tolerated dose (MTD). Number of participants with DLTs has been reported.

Blood pressure was measured in a semi-supine position after 5 minutes of rest. Blood pressure was measured before start of first chemotherapy infusion and within 20 minutes before start of GSK3052230 infusion on Day 1 of every cycle and Baseline. Baseline is defined as the most recent, non-missing value prior to or on the first study GSK3052230 treatment dose date. Change from Baseline is calculated as visit value minus Baseline value. The worst-case post-Baseline values has been presented. NA indicates that data were not available as standard deviation could not be calculated for a single participant. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Heart rate was measured in a semi-supine position after 5 minutes of rest. Heart rate was measured before start of first chemotherapy infusion and within 20 minutes before start of GSK3052230 infusion on Day 1 of every cycle and Baseline. Baseline is defined as the most recent, non-missing value prior to or on the first study GSK3052230 treatment dose date. Change from Baseline is calculated as visit value minus Baseline value. The worst-case post-Baseline values has been presented.

Temperature was measured in a semi-supine position after 5 minutes of rest. Temperature was measured before start of first chemotherapy infusion and within 20 minutes before start of GSK3052230 infusion on Day 1 of every cycle and Baseline. Baseline is defined as the most recent, non-missing value prior to or on the first study GSK3052230 treatment dose date. Change from Baseline is calculated as visit value minus Baseline value. The worst-case post-Baseline values has been presented.

A single 12-lead ECG was performed at the specified timepoints during the study where the participant was instructed to be in semi-recumbent position for 5 minutes before obtaining the ECG. An ECG machine that automatically calculated the heart rate and measures like the PR, QRS, QT, and corrected QT intervals. Number of participants with worst-case post-Baseline abnormal clinically significant findings and abnormal not clinically significant findings in ECG results has been reported.

Echocardiography scans were obtained at given time points using an echocardiogram and the findings for left ventricular ejection fraction (LVEF) were obtained. LVEF values at end of treatment (EOT) were recorded as no change or any increase and any decrease values. Only those participants available at the specified time points were analyzed.

Clinical chemistry parameters included potassium, sodium, chloride (Cl), total carbon dioxide (CO2), total and ionized calcium, magnesium, phosphate, albumin, glucose (fasting), Blood urea nitrogen (BUN), creatinine (Cr), uric acid, creatinine clearance, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (GGT), alkaline phosphatase, Total bilirubin (T. Bil), and Direct bilirubin (D. Bil), total T3 and T4, free T4, amylase, lipase, prothrombin time, partial thromboplastin time, international normalized ratio, and fibrinogen. Baseline is defined as the most recent, non-missing value prior to or on the first study GSK3052230 treatment dose date. Change from Baseline is calculated as visit value minus Baseline value. Clinical chemistry parameters with change from Baseline with respect to normal range only has been presented. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Urinalysis parameters included urine protein, urine glucose, urine ketones and occult blood were assessed. Dipstick test was performed for routine urinalysis. Abnormal values such as trace, 1+, 2+, 3+, 4+, \>1000, \>=1000, and \>10 have been reported.

Hematology parameters included platelet Count, red blood cell (RBC) Count, hemoglobin, absolute white blood cell (WBC) Count, absolute neutrophils (Neu), absolute lymphocytes (Lym), absolute monocytes (Mono), absolute eosinophils (Eos), absolute basophils (Baso). Baseline is defined as the most recent, non-missing value prior to or on the first study GSK3052230 treatment dose date. Change from Baseline is calculated as visit value minus Baseline value. Hematology parameters with worst-case change from Baseline with respect to normal range only has been presented. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

The MTD is defined as the highest dose level tested at which \< 33 percent of participants experience a DLT. In cases when MTD is not reached dose was described as the MFD.

Best response defined as complete response (CR:disappearance of all target. Any pathological lymph nodes \< 10 millimeter \[mm\] in the short axis) or partial response (PR at least a 30 percent decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters), stable disease (SD neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease) or progressive disease (PR at least a 20 percent increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started. In addition, the sum must have an absolute increase from nadir of 5 mm) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or modified RECIST. Best response as per RECIST version 1.1 for Arm A and B participants has been reported. Best response according to RECIST version 1.1 or modified RECIST for Arm C participants has been reported.

Overall Response Rate (ORR) is defined as the percentage of participants achieving a confirmed Complete response (CR) or Partial response (PR) from the start of treatment until disease progression as per RECIST version 1.1 or modified RECIST for participants in Arm C. This was determined based on Investigator assessments of response. 95% confidence intervals (CI) are calculated based on the unconditional exact method. ORR as per RECIST vesrion 1.1 for Arm A and B has been reported. ORR as per RECIST version 1.1 and modified RECIST version 1.1 for Arm C has been reported. The study population used for decision-making at the interim analyses during the dose expansion cohorts of the study arms is termed as the All Evaluable Participants Population. NA indicates 0 participants met ORR criteria therefore no dispersion.

PFS is defined as the interval between first dose of GSK3052230 and the earliest date of disease progression or death due to any cause by investigator assessment per RECIST 1.1 (for Arm A and B participants) or modified RECIST (for Arm C participants). For participants who do not progress or die, PFS was censored at the time of last radiological scan. Participants who discontinued study with no post-treatment tumor assessment were censored at date of first dose of study drug. Mean and 95 percent CI has been reported. NA indicates that data were not available as only 1 participant had event, other two censored therefore there is no confidence interval.

Serial blood sample were collected at an indicated time points. A nonlinear mixed effects model was used to determine clearances. The Pharmacokinetic Population (PK) consisted of all participants in the All Treated Subject Population for whom a blood sample for pharmacokinetics was obtained and analyzed. Plasma GSK3052230 concentration-time data were to be combined with data from other studies to be analyzed using a population PK approach. However, other studies with GSK3052230 were not performed and thus no population PK analyses were done.

Serial blood sample were collected at an indicated time points. A nonlinear mixed effects model was used to determine volume distribution. Plasma GSK3052230 concentration-time data were to be combined with data from other studies to be analyzed using a population PK approach. However, other studies with GSK3052230 were not performed and thus no population PK analyses were done.

Relevant covariates included parameters like age, weight and disease related covariates. Plasma GSK3052230 concentration-time data were to be combined with data from other studies to be analyzed using a population PK approach. However, other studies with GSK3052230 were not performed and thus no population PK analyses were done.

FVC is the total amount of air exhaled during the Forced Expiratory Volume test. Baseline is defined as the most recent, non-missing value prior to or on the first study GSK3052230 treatment dose date. Change from Baseline is calculated as visit value minus Baseline value. Assessment of FVC was done on Day 1 of every odd cycle for Arm C participants with MPM. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates that data were not available as standard deviation could not be calculated for a single participant.

GlaxoSmithKline

Participants in Arm A received 5 milligram per kilogram (mg/kg) GSK3052230 along with 200 mg per meter square (mg/m\^2) of Paclitaxel plus Area under curve (AUC) 6 that is (i.e.) 900 mg Carboplatin

5 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A

Participants in Arm A received 10 mg/kg GSK3052230 along with 200 mg/m\^2 of Paclitaxel plus AUC 6 i.e. 900 mg Carboplatin

10 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A

Participants in Arm A received 20 mg/kg GSK3052230 along with 200 mg/m\^2 of Paclitaxel plus AUC 6 i.e. 900 mg Carboplatin

20 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A

Participants in Arm B received 5 mg/kg GSK3052230 along with 75 mg/m\^2 Docetaxel

5 mg/kg GSK3052230 + Docetaxel: Arm B

Participants in Arm B received 10 mg/kg GSK3052230 along with 75 mg/m\^2 Docetaxel

10 mg/kg GSK3052230 + Docetaxel: Arm B

Participants in Arm B received 20 mg/kg GSK3052230 along with 75 mg/m\^2 Docetaxel

20 mg/kg GSK3052230 + Docetaxel: Arm B

Participants in Arm C received 10 mg/kg GSK3052230 along with 500 mg/m\^2 Pemetrexed plus 75 mg/m\^2 Cisplatin

10 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C

Participants in Arm C received 15 mg/kg GSK3052230 along with 500 mg/m\^2 Pemetrexed plus 75 mg/m\^2 Cisplatin

15 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C

Participants in Arm C received 20 mg/kg GSK3052230 along with 500 mg/m\^2 Pemetrexed plus 75 mg/m\^2 Cisplatin

20 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C

Total

Age, Continuous

Sex: Female, Male

Race/Ethnicity, Customized

GSK Response Center

Non-serious AEs

SAEs

Number of Participants With Non-serious Adverse Events (AEs) and Serious AEs (SAEs)

Number of Participants With Severe AEs and SAEs

Number of Participants Withdrew Due to AEs

Number of Participants With Dose Reduction

Number of Participants With Dose Delays

Treatment Duration With GSK3052230

Number of Participants With Dose-Limiting Toxicities (DLT)

DBP, n=3, 2, 9, 3, 2, 2, 3, 21, 5

SBP, n=3, 1, 13, 2, 2, 2, 3, 21, 4

Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

All Treated Subjects Population. Number of par. analyzed \> number of par. started in the study, as these were bi-directional vital signs tests. Heart rate had both clinically significant low and high ranges and there were par. who experienced both worst case post-Baseline values.Only those par. available at the specified time points were analyzed.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study to Evaluate GSK3052230 in Combination With Paclitaxel and Carboplatin, or Docetaxel or as Single Agent in Subjects With Solid Malignancies and Deregulated Fibroblast Growth Factor (FGF) Pathway Signaling	NCT01868022	Neoplasms	GSK3052230 paclitaxel carboplatin docetaxel pemetrexed cisplatin	18 Years -	GlaxoSmithKline
Study to Evaluate GSK3052230 in Combination With Paclitaxel and Carboplatin, or Docetaxel or as Single Agent in Subjects With Solid Malignancies and Deregulated Fibroblast Growth Factor (FGF) Pathway Signaling	NCT01868022	Neoplasms	GSK3052230 paclitaxel carboplatin docetaxel pemetrexed cisplatin	18 Years -	GlaxoSmithKline
Study to Evaluate GSK3052230 in Combination With Paclitaxel and Carboplatin, or Docetaxel or as Single Agent in Subjects With Solid Malignancies and Deregulated Fibroblast Growth Factor (FGF) Pathway Signaling	NCT01868022	Neoplasms	GSK3052230 paclitaxel carboplatin docetaxel pemetrexed cisplatin	18 Years -	GlaxoSmithKline

Spots Global Cancer Trial Database for gsk3052230

Every month we try and update this database with for gsk3052230 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for gsk3052230

Every month we try and update this database with for gsk3052230 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for gsk3052230 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.