Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Pharmaceutical Solutions

Docetaxel

Lenograstim

Mitogens

Trametinib

Tubulin Modulators

Antimitotic Agents

Protein Kinase Inhibitors

Enzyme Inhibitors

Participants will receive Trametinib once daily for 21 days of each cycle + Intravenous Docetaxel once every three weeks over at least a one-hour infusion + Filgrastim (growth factor) subcutaneous injection once daily for prophylactic use.

Biconvex film coated oral tablets for once daily use with unit dosage strength of 0.5mg and 2.0 mg for dose level of 2.0mg, 1.5mg, 1.0mg, and 0.5mg

Yellow or brownish yellow solution for injections with unit dosage strength of 20mg and 80 mg for intravenous infusion once every 3 weeks over at least one-hour infusion

Clear and colorless solution for once daily sub-cutaneous injection with unit dosage strength of 75 micrograms (mcg) for dose level of 50 mcg/meter\^2 or 75 mcg/body

Filgrastim

GSK Clinical Trials

The primary purpose of this study is to evaluate the safety and tolerability of the combination therapy of trametinib and docetaxel with growth factor support in Japanese subjects with Stage IV or a postoperative recurrence non-small cell lung cancer (NSCLC). This study data will be used for making decision for further Japanese development plan for NSCLC. Six evaluable subjects will be enrolled in a dose level to evaluate the safety and tolerability of the combination treatment. Dose-limiting toxicity will be assessed during the first 21 days of combination therapy.

Safety and Tolerability of Trametinib in Combination With Docetaxel in Japanese Subjects With Non-small Cell Lung Cancer

An Open-Label, Phase Ib Study to Assess the Safety and Tolerability of GSK1120212 in Combination With Docetaxel in Japanese Subjects With Non-small Cell Lung Cancer

Laboratory parameters include: hematology, clinical chemistry, coagulation tests and urinalysis tests.

Vital sing measurement include: temperature, systolic blood pressure, diastolic blood pressure, heart rate, and blood oxygen saturation (SpO2)

AEs will be collected from the time the first dose of study treatment is administered until 30 days following discontinuation of study treatment regardless of initiation of a new cancer therapy or transfer to hospice

PK parameters include: area under the concentration time curve over dosing interval (AUC\[0 to tau\]), maximum observed concentration (Cmax), time of occurence of Cmax (tmax), and pre-dose (trough) concentration at the end of the dosing interval

PK parameters include: area under the concentration time curve from time zero (pre-dose) extrapolated to infinite time (AUC\[0 to infinite\]), area under the concentration time curve from time zero to last quantifiable concentration within subject across all treatments (AUC\[0 to t\]), Cmax, tmax, systemic clearance of parent drug (CL), and volume of distribution (V)

As per RECIST v1.1 the response will be assessed from target lesion as complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), not applicable (NA) or not evaluable (NE) and from non-target lesion as CR, Non-CR/Non-PD, NA or NE

GlaxoSmithKline

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Recurrence

Uterine Cervical Neoplasms

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

GSK1120212 (trametinib) 1.5 mg QD + GSK2141795 50 mg QD in 28 day cycles

Trametinib dose is 1.5 mg orally once per day

GSK1120212 (trametinib)

The dose of GSK2141795 is 50 mg orally once per day

GSK2141795

Ursula A. Matulonis, MD

This research study is evaluating the combination of two drugs called GSK1120212 (trametinib) and GSK2141795 as a possible treatment for recurrent or persistent cervical cancer. Trametinib and GSK2141795 are drugs that may stop cancer cells from growing. Trametinib is a MEK inhibitor - it blocks a protein called MEK that is commonly overactive in tumor cells. GSK2141795 is an AKT inhibitor which blocks a pathway in cancer cells that is commonly overactive in tumor cells called the PI3kinase pathway. In this research study, the investigator is looking to see whether the combination of Trametinib and GSK2141795 is useful in treating recurrent and persistent cervical cancer.

Additionally, the investigator is looking to see if participants whose tumors contain a particular genetic make-up will have better response to combination trametinib and GSK2141795. Participants' tumors will be tested for mutations in genes which could make some cancers more susceptible to trametinib and GSK2141795.

Before the research starts (screening): The participant will be asked to undergo some screening tests or procedures to find out if they can be in the research study. Many of these tests and procedures are likely to be part of regular cancer care and may be done even if it turns out that the participant does not take part in the research study. If the participant has had some of these tests or procedures recently, they may or may not have to be repeated.

* A medical history, which includes questions about the participant's health, current medications, and any allergies.
* Physical exam, including height and weight
* An eye exam, by an eye specialist
* Performance status, the investigator will ask the participant questions about how they are able to carry on with your usual activities.
* Vital signs, including blood pressure, pulse, body temperature and respiratory rate
* An assessment of the participant's tumor by CT (Computerized Tomography) scan or MRI (Magnetic Resonance Imaging), of their chest, stomach area, and pelvis.
* Blood tests (approximately 2-3 tablespoons) including hematology, chemistry, liver function, kidney function, blood sugar levels, blood clotting levels
* Electrocardiogram (EKG), a test to check the participant's heart's rhythm
* Echocardiogram (ECHO), a test to check the participant's heart's structure and function.
* Serum pregnancy test if the participant are capable of becoming pregnant

If the results of the above tests show that the participant is eligible to participate in the research study, the participant will begin the study treatment. If the participant does not meet the eligibility criteria, the participant will not be able to participate in this research study.

If these tests show that the participant is eligible to participate in the research study, the participant will begin the study treatment. If the participant does not meet the eligibility criteria, the participant will not be able to participate in this research study.

Additional research procedures to be performed at the time of screening:

- Archival tumor testing: During this study, additional tests will be performed on a sample of the participant's original tumor that has been stored in your institution's tissue banks. These tests will be performed on tumor tissue samples from previous biopsies or surgeries for the participant's cancer. The research done on these samples will involve looking at DNA and proteins in the participant's cancer to see if researchers can learn more about the participant's type of cancer and understand how trametinib and GSK2141795 might work on their tumor. Testing of this sample will not require the participant to undergo any additional procedures.

TISSUE COLLECTIONS/OWNERSHIP: Participation in this protocol involves providing specimen(s) of the participant's tissue. Please know that if the investigator leaves the institution, the research and the tissue might remain at the DF/HCC or might be transferred to another institution.

* Additional Blood tests: Approximately 2 tablespoons of blood will be collected for research testing. This testing will involve looking at DNA and proteins in the participant's blood to compare them with those seen in their cancer. This will be drawn before the participant begin taking the study drug. These research sample collections are a required part of this research study. If the participant does not wish to undergo these procedures, the participant may not participate in this research study.
* Optional pre and post tumor biopsies: Before the participant begin receiving the study drug, your doctor will arrange for a procedure where your tumor will be biopsied. Your entire tumor or part of your tumor might be removed (excisional biopsy) or a small sample of the tumor might be removed using a needle (needle biopsy, fine needle aspirate) with guidance under radiographic studies. This will also occur before the participant begins treatment and between 2-4 weeks after treatment has started.

After the screening procedures confirm that the participant is eligible to participate in the research study:

Study Drugs:

If the participant decides to take part in this research study, the participant will be given a study drug diary for each treatment cycle. The participant will be asked to complete a drug diary to record when they took each dose or to give a reason if the participant did not take the study drugs. At the end of each cycle, the participant should return the pill bottles and all of the remaining pills prior to starting the next cycle. The participant will receive a new set of pills and new diary if the participant is to continue the next cycle.

Clinical Exams: During all cycles the participant will have a physical exam, and will be asked questions about their general health and specific questions about any problems that they might having and any medications the participant may be taking.

The participant can expect the following while they are a participant on this study.

At the beginning of each cycle (one cycle equals 28 days):

* Recording of any health problems, including side effects of the study drugs
* List of medications taken since the last visit
* Physical examination (including measurement of vital signs, such as blood pressure, breathing rate, heart rate, temperature and weight)
* Evaluation of the participant's performance status (the ability to carry on daily activities)
* Blood samples (approximately 2-3 tablespoons of blood will be taken) to evaluate the participant's blood counts, electrolytes, liver function, kidney function and blood sugar levels.
* EKG, a test to check the participant's heart's rhythm. This will be performed at the start on each cycle.

Once a week during the first cycle:

* The participant will be called by a member of the study team to record any health problems, including side effects from the study drugs and any changes in medications.
* Blood samples (approximately 1 teaspoon of blood will be taken) to evaluate their blood sugar levels. This can be done at a lab close to home. If the participant's doctor thinks that their blood sugars need further monitoring, the participant may have continued blood samples drawn to check their blood sugar weekly or daily past the first cycle.

Every 2 cycles:

* Blood samples (approximately 1 teaspoon of blood will be taken) to evaluate the participant's HgbA1C, a test that evaluates their blood sugar levels over a period of time. This can be done at a lab close to home.
* CT scan or MRI of your chest, stomach area, and pelvis to see if the participant's cancer is increasing, decreasing, or staying the same size. If the cancer is decreasing, the participant's doctor may schedule the participant for another CT scan in about one month to check it again.
* ECHO, a test to check the participant's heart's structure and function

At the end of the study:

* Recording of any health problems, including any side effects from the study drugs.
* List of medications taken since the last visit
* Physical examination (including measurement of the participant's vital signs, such as blood pressure, breathing rate, heart rate, temperature, and weight.)
* Evaluation of the participant's performance status (their ability to carry on daily activities).
* Blood samples (approximately 2-3 tablespoons of blood will be taken) to evaluate the participant's blood counts, electrolytes, liver function, kidney function, blood sugar level, and HgbA1C.

After the final dose of the study drug:

The investigator would like to keep track of the participant's medical condition for up to 3 years after the participant completes the study. The investigator would like to do this by calling the participant on the telephone or seeing the participant in clinic for evaluation of their status, disease and current therapy. Keeping in touch with the participant and checking their condition routinely helps us look at the long-term effects of the research study.

GSK1120212+GSK2141795 for Cervical Cancer

A Single Arm, Single Stage Phase II Trial of GSK1120212 and GSK2141795 in Persistent or Recurrent Cervical Cancer

Response rate will be assessed by RECIST version 1.1.

The duration of progression-free (PFS) following initiation of therapy with GSK1120212 (trametinib) and GSK2141795 will be measured.

Toxicity was assessed for this combination by version 4.0 of the NCI Common Terminology Criteria for Adverse Events (CTCAE) in this cohort of patients. Toxicities reported were deemed related to study treatment.

The mutation and co-mutation rates of genes in the PI3K and RAS ERK signaling pathways in recurrent cervical cancer will be interrogated using high throughput targeted mutational analysis on participant tumor samples.

Overall survival will be determined for subjects on this study

Novartis

National Comprehensive Cancer Network

Dana-Farber Cancer Institute

Principal Investigator

GSK1120212 (trametinib) 1.5 mg QD + GSK2141795 50 mg QD in 28 day cycles

GSK1120212 (trametinib): Trametinib dose is 1.5 mg orally once per day

GSK2141795: The dose of GSK2141795 is 50 mg orally once per day

GSK1120212 (Trametinib) and GSK2141795

Age, Categorical

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Ursula Matulonis

Response rate assessed by RECIST version 1.1.

Response Rate for the Combination of GSK1120212 (Trametinib) and GSK2141795 in Patients With Recurrent or Persistent Cervical Cancer.

PFS events were determined by RECIST 1.1, clinical progression and death.

Duration of Progression-free (PFS)

Toxicity of GSK1120212 (Trametinib) and GSK2141795 as Measured by the Number of Participants With Adverse Events

Adenocarcinoma

Squamous Cell Carcinoma

Mucinous

Observed mutations and amplifications in genes related to PI3K or RAS signaling in the 13 patients with tissue available for testing. One patient did not have archival tissue available for testing, five patients did not have detected alterations.

Mutation and Co-mutation Rates of Genes in the PI3K and RAS ERK Signaling Pathways in Recurrent Cervical Cancer Using High Throughput Targeted Mutational Analysis on Participant Tumor Samples.

Overall Survival

Overall Study

Digestive System Diseases

Rare Diseases

Biliary Tract Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Biliary Tract Diseases

Gastrointestinal Diseases

Biliary Tract Cancer

Gemcitabine

Subjects will receive, trametinib once daily as a single tablet of 2 mg administered orally with eight ounces of water under fasting conditions either one hour before or 2 hours after a meal.

Subjects will receive on Day 1, trametinib as four tablets of 0.5 mg administered orally with eight ounces of water under fasting conditions either one hour before or 2 hours after a meal.

Subjects will receive Day 2 onwards, trametinib once daily as a single tablet of 2 mg administered orally with eight ounces of water under fasting conditions either one hour before or 2 hours after a meal.

Trametinib (single tablet)

Trametinib (Multiple tablet)

This is a Phase IIa, open-label, single-arm, multi-center study to evaluate the efficacy and safety of orally administered MEK inhibitor trametinib as the second line in subjects with advanced or metastatic biliary tract cancers (BTC) in Japanese population. The primary endpoint of this study is 12 week non-progressive disease (PD) rate defined as the percentage of subjects without progression at Week 12. As a sub-study, pharmacokinetics (PK) of four tablets of 0.5 milligram (mg) tablet, or one tablet of 2 mg tablet to achieve 2 mg daily regimen will be assessed to evaluate the pharmacokinetics of trametinib in Japanese population.

Eligible subjects will be randomized to receive trametinib at the recommended Phase II dose of 2 mg every day as one 2 mg tablet or four 0.5 mg tablets on Day 1. From Day 2 until disease progression or withdrawal from the study treatment, all subjects will receive one tablet of 2 mg trametinib . Disease assessment will be performed every 8 week. Translational research is also planned to evaluate the potential blood or tumor tissue-derived biomarkers for biological activity, and sensitivity or resistance to treatment with trametinib .

A Phase IIa Study of the MEK Inhibitor Trametinib Monotherapy in the Treatment of Biliary Tract Cancers

A Phase IIa Study of the MEK Inhibitor GSK1120212 Monotherapy in the Treatment of Gemcitabine Refractory Locally Advanced, Recurrent or Metastatic Biliary Tract Cancers

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the diameters of target lesions; Stable Disease(SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; Progressive Disease(PD), At least a 20% increase in the sum of the diameters of target lesions. Non-PD = CR + PR + SD.

Twelve week non-progressive disease (PD) at Week 12 was evaluated by computed tomography. Non- PD was calculated as the sum of complete response (CR), partial response (PR), and stable disease (SD).

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. 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 or Protocol-Specific SAEs

Interstitial lung disease markers KL-6 assessments were carried out at Baseline (Day 1), Week 12, Week 20, Week 24, Week 28, Week 32, and Week 36

Interstitial lung disease marker Surfactant Protein D assessments were carried out at Baseline (Day 1), Week 12, and Week 28

Shift from baseline was calculated as the post baseline value minus the baseline value for albumin, alkalaine phosphatase (AP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, creatine kinase (CK), creatinine, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, and phosphate. A Worst Post Baseline (WPB) grade shift is defined as the worst change that occurred at any measured timepoint during the treatment period. Grading was determined by the NCI Common Terminology Criteria for Adverse Events Version 3.0 (NCI-CTCAE). Participants with missing baseline grade were designated a baseline grade of 0.

Shift from baseline was calculated as the post baseline value minus the baseline value for activated partial thromboplastin time (APTT) and prothrombin time (PT). A Worst Post Baseline (WPB) grade shift is defined as the worst change that occurred at any measured timepoint during the treatment period. Grading was determined by the NCI Common Terminology Criteria for Adverse Events Version 3.0 (NCI-CTCAE). Participants with missing baseline grade were designated a baseline grade of 0.

Shift from baseline was calculated as the post baseline value minus the baseline value for hemoglobin, lymphocytes, neutrophils, platelets, and leukocytes. A Worst Post Baseline (WPB) grade shift is defined as the worst change that occurred at any measured timepoint during the treatment period. Grading was determined by the NCI Common Terminology Criteria for Adverse Events Version 3.0 (NCI-CTCAE). Participants with missing baseline grade were designated a baseline grade of 0.

Change from baseline was calculated as the post baseline value minus the baseline value for cancer antigen 19-9 (CA 19-9), chloride, lactate dehydrogenase (LDH), and urea. A Worst Post Baseline (WPB) change is defined as the worst change that occurred at any measured timepoint during the treatment period. Measurements were designated as either Decreased to Low (DTL) or Increased to High (ITH) or Change to Normal/No Change (CN/NC). Participants with missing baseline measurements or visit measurements were considered to be missing. Participants were counted twice if the participant Decreased to Low and Increased to High.

Change from baseline was calculated as the post baseline value minus the baseline value for prothrombin time (PT). A Worst Post Baseline (WPB) change is defined as the worst change that occurred at any measured timepoint during the treatment period. Measurements were designated as either Decreased to Low (DTL) or Increased to High (ITH) or Change to Normal/No Change (CN/NC). Participants with missing baseline measurements or visit measurements were considered to be missing. Participants were counted twice if the participant Decreased to Low and Increased to High.

Change from baseline was calculated as the post baseline value minus the baseline value for basophils, eosinophils, and monocytes. A Worst Post Baseline (WPB) change is defined as the worst change that occurred at any measured timepoint during the treatment period. Measurements were designated as either Decreased to Low (DTL) or Increased to High (ITH) or Change to Normal/No Change (CN/NC). Participants with missing baseline measurements or visit measurements were considered to be missing. Participants were counted twice if the participant Decreased to Low and Increased to High.

Change from baseline was calculated as the post baseline value minus the baseline value for carcinoembryonic antigen (CEA). A Worst Post Baseline (WPB) change is defined as the worst change that occurred at any measured timepoint during the treatment period. Measurements were designated as either Decreased to Low (DTL) or Increased to High (ITH) or Change to Normal/No Change (CN/NC). Participants with missing baseline measurements or visit measurements were considered to be missing. Participants were counted twice if the participant Decreased to Low and Increased to High.

Body temperature was categorized as Decrease to \<=35; Change to Normal or No Change and Increase to \>=38. Change from baseline was calculated as the post baseline value minus the baseline value. A Worst Post Baseline (WPB) change is defined as the worst change that occurred at any measured timepoint during the treatment period. Participants with missing baseline measurements or visit measurements were considered to be missing.

Systolic and diastolic blood pressure was measured after sitting for at least 5 minutes. Systolic blood pressure (SBP) was categorized as: Grade 0 (\<120), Grade 1 (\>=120-\<140), Grade 2 (\>=140-\<160) and Grade 3 (\>=160). Diastolic blood pressure (DBP) was categorized as Grade 0 (\<80), Grade 1 (\>=80-\<90), Grade 2 (\>=90-\<100), and Grade 3 (\>=100). Change from baseline was calculated as the post baseline value minus the baseline value. A Worst Post Baseline (WPB) change is defined as the worst change that occurred at any measured timepoint during the treatment period. Participants with missing baseline measurements or visit measurements were considered to be missing.

Pulse rate was categorized as Decrease to \<60, Change to Normal or No Change, and Increase to \>100. Change from baseline was calculated as the post baseline value minus the baseline value. A Worst Post Baseline (WPB) change is defined as the worst change that occurred at any measured timepoint during the treatment period. Participants with missing baseline measurements or visit measurements were considered to be missing.

Oxygen Saturation was measured at Baseline (Day 1), Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32 and Week 36. For records occurring after baseline, change from baseline was calculated as the post baseline value minus the baseline value. When either the baseline or visit value was missing, the change from baseline was considered to be missing.

Progression-Free Survival (PFS) is defined as the interval of time (in weeks) between the date of randomization and the earlier of the date of disease progression and the date of death due to any cause. Disease progression was based on the assessments by the Investigator. If a participant received subsequent anti-cancer therapy prior to the date of documented progression or death, PFS in the participant was censored at the last adequate assessment prior the initiation of the new anti-cancer therapy. Otherwise, if a participant did not have a documented date of progression or death, PFS in the participant was censored at the last adequate assessment.

Progression-Free Survival (PFS) is defined as the interval of time (in weeks) between the date of randomization and the earlier of the date of disease progression and the date of death due to any cause. Disease progression was based on the assessments by the independent radiologist. If a participant received subsequent anti-cancer therapy prior to the date of documented progression or death, PFS in the participant was censored at the last adequate assessment prior the initiation of the new anti-cancer therapy. Otherwise, if a participant did not have a documented date of progression or death, PFS in the participant was censored at the last adequate assessment.

Overall Survival (OS) is defined as the interval of time (in weeks) between the date of randomization and the date of death due to any cause. For participants that did not die, time of death was censored at the date of last contact. The date of death was taken from that recorded on the Record of Death page. Death on study due to any cause was included. One year OS was calculated from Kaplan-Meier estimates.

Overall Response Rate (ORR) is defined as the number of participants achieving a confirmed CR or PR per RECIST 1.1 criteria from the start of treatment until disease progression or the start of new anti-cancer therapy. ORR was based on responses from the Investigator assessment of best overall response, the best overall response is the best response recorded from the start of the treatment until disease progression/recurrence. ORR is calculated as CR + PR.

Overall Response Rate (ORR) is defined as the number of participants achieving a confirmed CR or PR per RECIST 1.1 criteria from the start of treatment until disease progression or the start of new anti-cancer therapy. ORR was based on responses from the Independent Radiologist assessment of best overall response, the best overall response is the best response recorded from the start of the treatment until disease progression/recurrence. ORR is calculated as CR + PR.

Time to response (TTR) event was defined as achievement of a confirmed CR or PR, as the time from date of randomization until date of first documented evidence of CR or PR (whichever status is recorded first). If a participant received subsequent anti-cancer therapy prior to the date of documented progression or death, progression free survival (PFS) in the participant was censored at the last adequate assessment prior the initiation of the new anti-cancer therapy. Otherwise, if a participant did not have a documented date of progression or death, PFS in the participant was censored at the last adequate assessment.

Time to response (TTR) event was defined as achievement of a confirmed CR or PR, as the time from date of randomization until date of first documented evidence of CR or PR (whichever status is recorded first). If a participant received subsequent anti-cancer therapy prior to the date of documented progression or death, progression free survival (PFS) in the participant was censored at the last adequate assessment prior the initiation of the new anti-cancer therapy. Otherwise, if a participant did not have a documented date of progression or death, PFS in the participant was censored at the last adequate assessment. Only 1 participant reached PR therefore estimated time to response cannot be presented. The time to response for this patient is presented as the actual number of weeks to PR.

Duration of response was summarized for participants with a confirmed CR or PR and is defined as the time (in weeks) from the initial response (CR/PR) to first documented disease progression or death due to any cause. If a participant received subsequent anti-cancer therapy prior to the date of documented progression or death, PFS in the participant was censored at the last adequate assessment prior the initiation of the new anti-cancer therapy. Otherwise, if a participant did not have a documented date of progression or death, PFS in the participant was censored at the last adequate assessment.

SAEs and non-serious AEs are reported for members of the Intent-to-Treat (ITT) Population: all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.

Participants received GSK1120212 at 2 milligram (mg), either as four tablets of 0.5 mg or one tablet of 2 mg at Day 1. At Day 2 and for the remaining study period, participants received continuous daily dosing of one tablet of 2 mg GSK1120212 once-daily until disease progression or death or until study treatment stopping criteria was met.

GSK1120212 2 mg

Age, Continuous

Asian - Japanese Heritage

Race/Ethnicity, Customized

GSK Response Center

Complete Response (CR)

Partial Response (PR)

Stable Disease (SD)

Non-CR/Non-PD

Progressive Disease (PD)

Not Evaluable (NE)

Progressive Disease before week 12

Censored before week 12

CR+PR+SD+Non-CR/Non-PD

Intent-to-Treat (ITT) Population: all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.

Number of Participants With Indicated Non-progressive Disease as Assessed by Investigator Per Response Evaluation Criteria In Solid Tumor Version 1.1 (RECIST 1.1) at Week 12

Number of Participants With Indicated Non-progressive Disease as Assessed by Independent Radiologist Per Response Evaluation Criteria In Solid Tumor Version 1.1 (RECIST 1.1) at Week 12

Any AE

Any SAE

Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)

Baseline, n=20

Week 12, n=3

Week 20, n=1

Week 24, n=1

Week 28, n=2

Week 32, n=1

Week 36, n=1

Intent-to-Treat (ITT) Population: all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period. Only those participants with analyzable data at the indicated time point were assessed.

Expression of Interstitial Lung Disease Marker KL-6

Baseline, n=17

Week 12, n=2

Week 28, n=1

Intent-to-Treat (ITT) Population: all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period. Only those participants with analyzable data at the indicated time point were assessed (represented by n=x).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Safety and Tolerability of Trametinib in Combination With Docetaxel in Japanese Subjects With Non-small Cell Lung Cancer	NCT01938456	Lung Cancer, No...	Trametinib Docetaxel Filgrastim	20 Years -	GlaxoSmithKline
GSK1120212+GSK2141795 for Cervical Cancer	NCT01958112	Cervical Cancer	GSK1120212 (tra... GSK2141795	18 Years -	Dana-Farber Cancer Institute
A Phase IIa Study of the MEK Inhibitor Trametinib Monotherapy in the Treatment of Biliary Tract Cancers	NCT01943864	Cancer	Trametinib (sin... Trametinib (Mul...	20 Years - 80 Years	GlaxoSmithKline

Spots Global Cancer Trial Database for gsk1120212 (trametinib)