Trial Outcomes & Findings for LGX818 in Combination With Agents (MEK162; BKM120; LEE011; BGJ398; INC280) in Advanced BRAF Melanoma (NCT NCT01820364)

NCT ID: NCT01820364

Last Updated: 2017-01-09

Results Overview

Response Evaluation Criteria In Solid Tumors (RECIST) is a set of published rules that define the status of tumors in cancer patients during a specific treatment. The Overall Response Rate was calculated according to the RECIST criteria, as per investigator assessment. Per RECIST guidelines: * Complete Response (CR) is the Disappearance of all target lesions. * Partial Response (PR) is at least a 30% decrease in the sum of diameters of target lesions. * Progressive Disease (PD) is the at least a 20% increase in the sum of diameters of target lesions. * Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

15 participants

Primary outcome timeframe

Baseline through study completion (approximately 2 years)

Results posted on

2017-01-09

Participant Flow

The study began on 04-Nov-2013 (First Subject First Visit) to the CLGX818X2102 (LOGIC 1) study. A total of 15 subjects were enrolled. The last subject's last visit occurred on 23-Mar-2015. Not completed subjects represents subjects that stopped treatment early, due to the corresponding reason.

After careful evaluation of slow enrollment and the BRAF-mutant melanoma treatment landscape, recruitment was permanently halted on 26-Jul-2014. This recruitment halt was not a consequence of any safety concern and patients who were ongoing in the study continued to be treated as per protocol.

Participant milestones

Participant milestones
Measure	Part I: LGX818 - Single Agent Subjects in Part I of the study received LGX818 as a single agent.	Part II: CLGX818 + MEK162 As per the original study design, Part II was to have five arms corresponding to the five potential combination treatments; however, only one patient was treated in this part of the study and received LGX818 in combination with MEK162.
Part I: LGX818 STARTED	15	0
Part I: LGX818 COMPLETED	1	0
Part I: LGX818 NOT COMPLETED	14	0
Part II: LGX818 + MEK162 STARTED	0	1
Part II: LGX818 + MEK162 COMPLETED	0	0
Part II: LGX818 + MEK162 NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Part I: LGX818 - Single Agent Subjects in Part I of the study received LGX818 as a single agent.	Part II: CLGX818 + MEK162 As per the original study design, Part II was to have five arms corresponding to the five potential combination treatments; however, only one patient was treated in this part of the study and received LGX818 in combination with MEK162.
Part I: LGX818 Death	1	0
Part I: LGX818 Administrative Problems	3	0
Part I: LGX818 Adverse Event	6	0
Part I: LGX818 Disease Progression	4	0
Part II: LGX818 + MEK162 Study Termination	0	1

Baseline Characteristics

LGX818 in Combination With Agents (MEK162; BKM120; LEE011; BGJ398; INC280) in Advanced BRAF Melanoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part I: LGX818 - Single Agent n=15 Participants Subjects in Part I of the study received LGX818 as a single agent.
Age, Categorical <=18 years	0 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	12 Participants n=93 Participants
Age, Categorical >=65 years	3 Participants n=93 Participants
Age, Continuous	52.3 years STANDARD_DEVIATION 16.53 • n=93 Participants
Gender Female	7 Participants n=93 Participants
Gender Male	8 Participants n=93 Participants
Region of Enrollment United States	2 participants n=93 Participants
Region of Enrollment Australia	3 participants n=93 Participants
Region of Enrollment Switzerland	6 participants n=93 Participants
Region of Enrollment Germany	1 participants n=93 Participants
Region of Enrollment Spain	3 participants n=93 Participants
Weight	80.3 kilograms STANDARD_DEVIATION 19.11 • n=93 Participants
Height	171.8 centimeters STANDARD_DEVIATION 9.51 • n=93 Participants
WHO/ ECOG performance status 0	14 participants n=93 Participants
WHO/ ECOG performance status 1	1 participants n=93 Participants

PRIMARY outcome

Timeframe: Baseline through study completion (approximately 2 years)

Population: This analysis is comprised of the Full Analysis Set, which consists of all patients who received at least one dose of LGX818.

Outcome measures

Outcome measures
Measure	Part I: LGX818 - Single Agent n=15 Participants Subjects in Part I of the study received LGX818 as a single agent.	Part II: CLGX818 + MEK162 n=1 Participants As per the original study design, Part II was to have five arms corresponding to the five potential combination treatments; however, only one patient was treated in this part of the study and received LGX818 in combination with MEK162.
Tumor Response (Overall Response Rate) Per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Part I & Part II) Complete Response	1 participants	0 participants
Tumor Response (Overall Response Rate) Per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Part I & Part II) Partial Response	8 participants	0 participants
Tumor Response (Overall Response Rate) Per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Part I & Part II) Progressive Disease	1 participants	1 participants
Tumor Response (Overall Response Rate) Per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Part I & Part II) Stable Disease	2 participants	0 participants
Tumor Response (Overall Response Rate) Per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Part I & Part II) Unknown	3 participants	0 participants

SECONDARY outcome

Timeframe: Baseline through study completion (approximately 2 years)

Incidence of DLTs in Part II of the study was not evaluated due to an inadequate number of patients enrolled in Part II prior to the permanent recruitment halt of this study.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline through study completion (approximately 2 years)

Assessment of pharmacokinetic (PK) parameters and plasma concentration was not done due to an inadequate number of patients enrolled in Part II prior to the permanent recruitment halt of this study.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline through completion of Part I of the study (approximately 2 years)

Population: This analysis is comprised of the Full Analysis Set, which consists of all patients who received at least one dose of LGX818.

Outcome measures

Outcome measures
Measure	Part I: LGX818 - Single Agent n=15 Participants Subjects in Part I of the study received LGX818 as a single agent.	Part II: CLGX818 + MEK162 As per the original study design, Part II was to have five arms corresponding to the five potential combination treatments; however, only one patient was treated in this part of the study and received LGX818 in combination with MEK162.
Tumor Response (Overall Response Rate) Via Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Part I) Complete Response	1 participants	—
Tumor Response (Overall Response Rate) Via Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Part I) Partial Response	8 participants	—
Tumor Response (Overall Response Rate) Via Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Part I) Progressive Disease	1 participants	—
Tumor Response (Overall Response Rate) Via Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Part I) Stable Disease	2 participants	—
Tumor Response (Overall Response Rate) Via Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Part I) Unknown	3 participants	—

SECONDARY outcome

Timeframe: Entry to Part II of the study through study completion (approximately 22 days)

Population: This analysis group is comprised of the Full Analysis Set, which consists of all patients who received at least one dose of LGX818.

Outcome measures

Outcome measures
Measure	Part I: LGX818 - Single Agent n=1 Participants Subjects in Part I of the study received LGX818 as a single agent.	Part II: CLGX818 + MEK162 As per the original study design, Part II was to have five arms corresponding to the five potential combination treatments; however, only one patient was treated in this part of the study and received LGX818 in combination with MEK162.
Tumor Response (Overall Response Rate) Via Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Part II) Complete Response	0 participants	—
Tumor Response (Overall Response Rate) Via Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Part II) Partial Response	0 participants	—
Tumor Response (Overall Response Rate) Via Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Part II) Progressive Disease	1 participants	—
Tumor Response (Overall Response Rate) Via Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Part II) Stable Disease	0 participants	—
Tumor Response (Overall Response Rate) Via Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 (Part II) Unknown	0 participants	—

SECONDARY outcome

Timeframe: Baseline and at progression with LGX818 single agent treatment

Molecular status was not evaluated due to an inadequate number of patients enrolled in Part II prior to the permanent recruitment halt of this study.

Outcome measures

Outcome data not reported

Adverse Events

Part I: LGX818 - Single Agent

Serious events: 3 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Part I: LGX818 - Single Agent n=15 participants at risk Subjects in Part I of the study received LGX818 as a single agent.
Vascular disorders Hypotension	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases To Central Nervous System	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic Pain	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Cardiac disorders Atrial Fibrillation	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Respiratory, thoracic and mediastinal disorders Dyspnoea	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Blood and lymphatic system disorders Coagulopathy	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Psychiatric disorders Panic Attack	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Renal and urinary disorders Renal Failure Acute	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Renal and urinary disorders Urinary Retention	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Metabolism and nutrition disorders Dehydration	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Infections and infestations Pneumonia	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.

Other adverse events

Other adverse events
Measure	Part I: LGX818 - Single Agent n=15 participants at risk Subjects in Part I of the study received LGX818 as a single agent.
Vascular disorders Flushing	20.0% 3/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Vascular disorders Hypotension	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Melanocytic Naevus	13.3% 2/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin Papilloma	13.3% 2/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acrochordon	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Blepharal Papilloma	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pyogenic Granuloma	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Seborrhoeic Keratosis	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
General disorders Fatigue	60.0% 9/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
General disorders Asthenia	26.7% 4/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
General disorders Oedema Peripheral	20.0% 3/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
General disorders Face Oedema	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
General disorders Pyrexia	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Reproductive system and breast disorders Benign Prostatic Hyperplasia	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Reproductive system and breast disorders Breast Pain	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Reproductive system and breast disorders Menstruation Irregular	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Reproductive system and breast disorders Vaginal Haemorrhage	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Reproductive system and breast disorders Dyspnoea	13.3% 2/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Injury, poisoning and procedural complications Procedural Pain	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Injury, poisoning and procedural complications Toxicity To Various Agents	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Investigations Gamma-Glutamyltransferase Increased	13.3% 2/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Investigations Alanine Aminotransferase Increased	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Investigations Amylase Increased	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Investigations Blood Alkaline Phosphatase Increased	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Investigations Blood Cholesterol Increased	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Investigations Blood Creatinine Increased	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Investigations Electrocardiogram Qt Prolonged	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Investigations Haemoglobin Increased	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Investigations Lipase Increased	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Investigations Weight Decreased	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Cardiac disorders Atrial Fibrillation	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Cardiac disorders Long Qt Syndrome	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Respiratory, thoracic and mediastinal disorders Cough	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Blood and lymphatic system disorders Anaemia	33.3% 5/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Blood and lymphatic system disorders Leukocytosis	13.3% 2/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Blood and lymphatic system disorders Eosinophilia	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Blood and lymphatic system disorders Thrombocytopenia	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Nervous system disorders Headache	26.7% 4/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Nervous system disorders Dysgeusia	20.0% 3/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Nervous system disorders Aphasia	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Nervous system disorders Convulsion	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Nervous system disorders Dizziness	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Nervous system disorders Hypogeusia	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Nervous system disorders Neuralgia	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Nervous system disorders Paraesthesia	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Nervous system disorders Peripheral Sensorimotor Neuropathy	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Nervous system disorders Tremor	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Nervous system disorders VIIth Nerve Paralysis	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Nervous system disorders Insomnia	66.7% 10/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Eye disorders Cataract	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Eye disorders Conjunctival Hyperaemia	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Eye disorders Ophthalmoplegia	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Eye disorders Vision Blurred	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Ear and labyrinth disorders Ear Pain	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Gastrointestinal disorders Nausea	20.0% 3/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Gastrointestinal disorders Vomiting	20.0% 3/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Gastrointestinal disorders Constipation	13.3% 2/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Gastrointestinal disorders Abdominal Pain Upper	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Gastrointestinal disorders Dyspepsia	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Gastrointestinal disorders Gingival Bleeding	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Gastrointestinal disorders Haemorrhoidal Haemorrhage	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Gastrointestinal disorders Haemorrhoids	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Gastrointestinal disorders Inguinal Hernia	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Gastrointestinal disorders Rectal Haemorrhage	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Gastrointestinal disorders Tongue Coated	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Renal and urinary disorders Dysuria	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Renal and urinary disorders Haematuria	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Renal and urinary disorders Proteinuria	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Skin and subcutaneous tissue disorders Hyperkeratosis	80.0% 12/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Skin and subcutaneous tissue disorders Alopecia	66.7% 10/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Skin and subcutaneous tissue disorders Palmar-Plantar Erythrodysaesthesia Syndrome	60.0% 9/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Skin and subcutaneous tissue disorders Dry Skin	33.3% 5/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Skin and subcutaneous tissue disorders Rash	26.7% 4/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Skin and subcutaneous tissue disorders Rash Maculo-Papular	26.7% 4/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Skin and subcutaneous tissue disorders Erythema	20.0% 3/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Skin and subcutaneous tissue disorders Rash Papular	13.3% 2/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Skin and subcutaneous tissue disorders Granuloma Skin	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Skin and subcutaneous tissue disorders Palmar Erythema	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Skin and subcutaneous tissue disorders Papule	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Skin and subcutaneous tissue disorders Rash Macular	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Skin and subcutaneous tissue disorders Skin Hypertrophy	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Musculoskeletal and connective tissue disorders Arthralgia	40.0% 6/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Musculoskeletal and connective tissue disorders Myalgia	26.7% 4/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Musculoskeletal and connective tissue disorders Back Pain	20.0% 3/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Musculoskeletal and connective tissue disorders Muscular Weakness	20.0% 3/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Musculoskeletal and connective tissue disorders Musculoskeletal Pain	13.3% 2/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Musculoskeletal and connective tissue disorders Joint Swelling	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Musculoskeletal and connective tissue disorders Musculoskeletal Chest Pain	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Musculoskeletal and connective tissue disorders Pain In Extremity	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Endocrine disorders Hypothyroidism	13.3% 2/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Metabolism and nutrition disorders Decreased Appetite	26.7% 4/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Metabolism and nutrition disorders Hyperglycaemia	20.0% 3/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Metabolism and nutrition disorders Dehydration	13.3% 2/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Metabolism and nutrition disorders Hyperkalaemia	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Metabolism and nutrition disorders Hypertriglyceridaemia	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Metabolism and nutrition disorders Hypoalbuminaemia	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Metabolism and nutrition disorders Hypokalaemia	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Metabolism and nutrition disorders Hypophosphataemia	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Infections and infestations Anal Abscess	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Infections and infestations Folliculitis	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Infections and infestations Lower Respiratory Tract Infection	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Infections and infestations Oral Candidiasis	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Infections and infestations Upper Respiratory Tract Infection	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.
Infections and infestations Urinary Tract Infection	6.7% 1/15 • Adverse Events (AEs), Serious Adverse Events (SAEs), and Non-serious AEs were collected throughout the duration of the study, approximately 2 years. An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. This analysis group is the Safety Set, which is all patients from the Full Analysis Set who had at least one post-baseline safety assessment. Due to slow enrollment, the study was terminated on 26-July-2014, at which time 15 patients were enrolled of Phase I of the study. The last patient last visit date occurred on 23-March-2015. One patient with documented PD at study Day 146 entered into Part II of the study and received combination treatment of LGX818 450 mg plus MEK162 45 mg for two weeks. The patient experienced disease progression on Day 22 of Part II and discontinued the study.

Additional Information

Study Director

Array BioPharma, Inc.

Phone: 303-381-6604

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of the sponsor's agreements with its investigators may vary. However, the sponsor does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e.,data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER