SIGNATURE: MEK162 for Patients With RAS/RAF/MEK Activated Tumors

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01885195
• Collaborator: (none)
• Enrollment: 110
• Locations: 68
• Arm: 1
• Actual Duration (Months): 42
• Patients Per Site: 1.6
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this signal seeking study is to determine whether treatment with MEK162 demonstrates sufficient efficacy in select pathway-activated solid tumors and/or hematologic malignancies to warrant further study

Condition or Disease	Intervention/Treatment	Phase
Solid Tumor and Hematologic Malignancies	Drug: MEK162	Phase 2

Detailed Description

This is a phase II, open label study to determine the efficacy and safety of treatment with MEK162 in patients with a diagnosis of select solid tumors or hematological malignancies that have been pre-identified (prior to study consent) to have activations of the RAS/RAF/MEK pathway and whose disease has progressed on or after standard treatment.

Genomic profiling is becoming more accessible to patients and their physicians. This is a signal-seeking study to match patients with mutations in RAF, RAS, NF1 or MEK to the ATP-noncompetitive MEK 1/2 inhibitor, MEK162. Pre-identification of these mutations or activations in the pathway will be performed locally at a CLIA certified laboratory prior to screening for participation on the trial.

Once the patient has been identified, treating physicians who are qualified investigators may contact Novartis to consider enrollment in this study. For the purpose of this study, genomic profiling is not considered part of screening. Informed consent must be signed before any screening activities take place. Once eligibility (screening criteria met) has been confirmed by Novartis, the patient will initiate therapy with single agent MEK162. The patient may not receive any additional anti-cancer therapy during treatment with MEK162.

Patients will continue to receive study treatment until disease progression (assessed by RECIST 1.1 or appropriate hematologic response criteria), unacceptable toxicity, death or discontinuation from study treatment for any other reason (e.g., withdrawal of consent, start of a new anti-neoplastic therapy or at the discretion of the investigator), otherwise known as End of Treatment. All patients who discontinue from study treatment due to disease progression must have their progression clearly documented.

Disease assessment (per RECIST 1.1 or appropriate hematological response criteria) will be performed every 8 weeks (±4 days) after first dose of study drug (Day 1 of every odd cycle), until disease progression or end of treatment, whichever occurs first. The frequency of disease assessment may be reduced to every 12 weeks for patients who have at least 4 post-baseline disease assessments and are clinically stable (except AML and MM patients). Scans will be assessed locally by the investigator. After discontinuation of treatment, patients, regardless of reason for treatment discontinuation, will be followed for safety for 30 days after the last dose.

All patients will be followed for survival status every 3 months for 2 years after the last patient has enrolled in the study regardless of treatment discontinuation reason (except if consent is withdrawn or patient is lost to follow-up.)

Study Design

• Study Type: Interventional
• Actual Enrollment: 110 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Primary Purpose: Treatment
• Official Title: Modular Phase II Study to Link Targeted Therapy to Patients With Pathway Activated Tumors: Module 3 - MEK162 for Patients With RAS/RAF/MEK Activated Tumors
• Actual Study Start Date: Oct 10, 2013
• Actual Primary Completion Date: Oct 1, 2015
• Actual Study Completion Date: Apr 11, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MEK162 MEK162 will be dosed on a flat scale of 45 mg twice daily on a continuous dosing schedule.	Drug: MEK162; MEK162 will be dosed on a flat scale of 45 mg twice daily on a continuous dosing schedule.

Outcome Measures

Primary Outcome Measures

1. Clinical Benefit Rate (CBR) for Solid Tumors at Week 16 as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 [Week 16]

   CBR: participants with complete response (CR), partial response (PR) or stable disease (SD) for at least 16 weeks. As per RECIST 1.1, CR: disappearance of all target and non-target lesions, normalization of tumor marker level, pathological lymph nodes assigned as target or non-target lesions must have a reduction in short axis to less than (<) 10 millimeter (mm); PR: at least a 30 percent (%) decrease in sum of diameter of all target lesions, taking as reference the baseline sum of diameters; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters; PD: at least a 20% increase in sum of diameter of all measured target lesions, taking as reference smallest sum of diameter of all target lesions recorded at or after baseline, sum was also an absolute increase of at least 5 mm. Unequivocal progression of existing non-target lesions. Appearance of >=1 new target or non-target lesions.

2. CBR for Hematologic Tumors at Week 16: Multiple Myeloma [Week 16]

   CBR: participants with stringent complete response(sCR), CR, very good partial response(VGPR), PR/SD for at least 16 weeks. For hematologic tumors (multiple myeloma), sCR: negative immunofixation on serum, urine, disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow plus normal free light chain(FLC) ratio and absence of clonal cells in bone marrow by immunohistochemistry/immunofluorescence; CR: negative immunofixation on the serum, urine, disappearance of any soft tissue, plasmacytomas and <5% plasma cells in bone marrow; VGPR: serum,urine M-component detectable by immunofixation but not on electrophoresis or>=90% reduction in serum M-component plus urine M-component <100 mg/24 hr; PR: >50% reduction of serum M-protein and reduction in 24hr urinary M-protein by >90%/to <200 mg/24 hr; SD: not meeting criteria for CR, VGPR, PRor PD; PD: increase of >25% from lowest response value in serum M-component, urine M-component and bone marrow plasma cell percentage.

3. CBR for Hematologic Tumors at Week 16: Acute Myeloid Leukemia [Week 16]

   CBR: participants with complete remission (CR), CR with incomplete blood count recovery (CRi), partial remission (PR) and no resposne for at least 16 weeks. For hematologic tumors (acute myeloid leukemia); CR: as bone marrow- < 5% blasts, no blasts with auer rods, peripheral blood- neutrophils ≥1.0*10^9/L and/or platelets ≥100*10^9/L, ≤1% blasts, no evidence of extramedullary disease (such as CNS or soft tissue involvement), transfusion independent; CRi: all the CR criteria were involved but platelet and neutrophil transfusions were also allowed; PR: bone marrow- 50% or greater decrease (absolute range 5-25% blasts), < 5% of blasts contain auer rods, peripheral blood- neutrophils <1.0*10^9/L and/or platelets <100*10^9/L, no evidence of extramedullary disease; no response: in case a patient did not achieve CR, CRi, PR or relapse for an individual response assessment.

Secondary Outcome Measures

1. Overall Response Rate (ORR) as Per RECIST Version 1.1 [From the start of the treatment until disease progression (maximum up to 19.4 months)]

   ORR: percentage of participants with a best overall response (BOR) of CR or PR as assessed per RECIST version 1.1. BOR: the best response recorded from the start of the treatment until disease progression (PD). CR: disappearance of all target and non-target lesions, normalization of tumor marker level, pathological lymph nodes assigned as target or non-target lesions must have a reduction in short axis to less than <10 mm; PR: at least a 30 % decrease in sum of diameter of all target lesions, taking as reference the baseline sum of diameters; PD: at least a 20% increase in sum of diameter of all measured target lesions, taking as reference smallest sum of diameter of all target lesions recorded at or after baseline, sum was also an absolute increase of at least 5 mm. Unequivocal progression of existing non-target lesions. Appearance of >=1 new target or non-target lesions.

2. ORR for Hematologic Tumors: Multiple Myeloma [From the start of the treatment until disease progression (maximum up to 19.4 months)]

   ORR: percentage of participants with sCR, CR, VGPR or PR. For hematologic tumors (multiple myeloma), sCR: negative immunofixation on the serum, urine, disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow plus normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence; CR: CR: negative immunofixation on the serum, urine, disappearance of any soft tissue, plasmacytomas and <5% plasma cells in bone marrow; VGPR: serum and urine M-component detectable by immunofixation but not on electrophoresis or greater than equal to >=90% reduction in serum M-component plus urine M-component <100 mg per 24hour (hr); PR: >50% reduction of serum M-protein and reduction in 24 hr urinary M-protein by >90% or to <200 mg/24 hr.

3. ORR for Hematologic Tumors: Acute Myeloid Leukemia [From the start of the treatment until disease progression (maximum up to 19.4 months)]

   ORR: participants with complete remission (CR), CR with incomplete blood count recovery (CRi), partial remission (PR) and no resposne for at least 16 weeks. For hematologic tumors (acute myeloid leukemia); CR: as bone marrow- < 5% blasts, no blasts with auer rods, peripheral blood- neutrophils ≥1.0*10^9/L and/or platelets ≥100*10^9/L, ≤1% blasts, no evidence of extramedullary disease (such as CNS or soft tissue involvement), transfusion independent; CRi: all the CR criteria were involved but platelet and neutrophil transfusions were also allowed; PR: bone marrow- 50% or greater decrease (absolute range 5-25% blasts), < 5% of blasts contain auer rods, peripheral blood- neutrophils <1.0*10^9/L and/or platelets <100*10^9/L, no evidence of extramedullary disease.

4. Progression-free Survival (PFS) as Per RECIST Version 1.1 [From the date of first dose to the date of the first documented PD, censored date or death (maximum up to 19.4 months)]

   PFS was defined as the time from the date of first dose to the date of first documented PD or relapse or death due to any cause. PD: at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of existing non-target lesions. Appearance of >=1 new target or non-target lesions was also considered progression. PFS data was censored at date of last adequate tumor assessment.

5. Overall Survival (OS) [From the date of first dose to the date of death due to any cause (maximum up to 19.4 months)]

   OS was defined as the time from the date of first dose to the date of death due to any cause. If a participant was not known to have died, survival time was censored at the date of last contact.

6. Duration of Response (DOR) as Per RECIST Version 1.1 [From the first documented response (CR or PR) to the date of the first documented PD or death (maximum up to 19.4 months)]

   DOR was defined as the time from the first documented response (CR or PR) to the date of first documented disease progression, relapse or death due to any cause. As per RECIST 1.1, CR: disappearance of all target and non-target lesions, normalization of tumor marker level, pathological lymph nodes assigned as target or non-target lesions must have a reduction in short axis to <10 mm; PR: at least a 30% decrease in sum of diameter of all target lesions, taking as reference the baseline sum of diameters; PD: at least a 20% increase in sum of diameter of all measured target lesions, taking as reference smallest sum of diameter of all target lesions recorded at or after baseline, sum was also an absolute increase of at least 5 mm. Unequivocal progression of existing non-target lesions. Appearance of >=1 new target or non-target lesions. The DOR was determined only in participants whose best response was PR or greater.

7. Number of Participants With Treatment Emergent Adverse Events (TEAEs) Graded According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03 [From Baseline up to 30 days following the last dose of study treatment (maximum up to 21 months)]

   Adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated. Treatment-emergent adverse events were defined as new or worsening events that were collected from first study treatment date to last treatment date +30 days. AEs of all grades were reported.

8. Number of Participants With Vital Sign Abnormality of Greater Than or Equal to (>=) Grade 3 as Per CTCAE v4.03 [From Baseline up to 30 days following the last dose of study treatment (maximum up to 21 months)]

   Vital signs included hypertension, hypotension and weight decreased were reported. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated. Participants with grade 3 or higher vital sign abnormality are reported.

9. Number of Participants With Electrocardiogram (ECG) Abnormalities [From Baseline up to 30 days following the last dose of study treatment (maximum up to 21 months)]

   ECG abnormalities criteria included: 1) QTc interval adjusted according to Bazett formula (QTcF) in millisecond (msec): greater than equal to (>=) 450 to less than (<) 480, >=480 to <500, >=500, increase from baseline >=30, increase from baseline >=60; 2) QTc interval adjusted according to Fridericia formula (QTcB) (msec): >=450 to <480, >=480 to <500, >=500, increase from baseline >=30, increase from baseline >=60. 3) QT (msec): >=450 to <480, >=480 to <500, >=500, increase from baseline >=30, increase from baseline >=60.

10. Number of Participants With Shift From Baseline in Clinical Laboratory - Hematology Parameters [From Baseline up to 30 days following the last dose of study treatment (maximum up to 21 months)]

    Laboratory parameters included hematological and biochemistry parameters. Hematological parameters included neutrophils, platelets, prothrombin time, activated partial thromboplastin time, INR, fibrinogen. Number of participants with hematological abnormalities by grades (as per Common Terminology Criteria for Adverse Events (CTCAE version 4.03) were reported. Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Participants with a grade shift of 3 or more from baseline are reported in this outcome measure.

11. Number of Participants With Shift From Baseline in Clinical Laboratory - Biochemistry Parameters [From Baseline up to 30 days following the last dose of study treatment (maximum up to 21 months)]

    Laboratory parameters included hematological and biochemistry parameters. Biochemistry parameters included: creatinine, phosphorus, albumin, gamma-glutamyl transferase, aspartate transaminase, alanine aminotransferase, alkaline phosphatase, total bilirubin, uric acid, amylase, lipase, creatine kinase, total cholesterol and triglycerides. Number of participants with biochemistry test abnormalities by grades (CTCAE version 4.03) were reported. Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Participants with a grade shift of 3 or more from baseline are reported in this outcome measure.

12. Number of Participants With Shift From Baseline in Cardiac Imaging [From Baseline up to 30 days following the last dose of study treatment (maximum up to 21 months)]

    Number of Participants With Shift From Baseline in Cardiac Imaging were reported.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patient has a confirmed diagnosis of a select solid tumor (except for primary diagnosis of pancreatic cancer, biliary cancer, colorectal cancer, low grade serous ovarian cancer, melanoma) or hematologic malignancy (except for primary diagnosis of chronic myelomonocytic leukemia).

• Patients must be pre-identified as having a tumor with a mutation in RAF, RAS, NF1 or MEK at a CLIA certified laboratory

• Patient must have received at least one prior treatment for recurrent, metastatic and /or locally advanced disease and for whom no standard therapy options are anticipated to result in a durable remission.

• Patient must have progressive and measurable disease as per RECIST 1.1. or other appropriate hematological guidelines.

• Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1

Exclusion Criteria:

• Patient has received prior treatment with MEK162.

• Patients with primary CNS tumor or CNS tumor involvement

• History of retinal degenerative disease

• History or current evidence of central serous retinopathy (CSR) or retinal vein occlusion (RVO)

• Any ophthalmopathy visible at screening that would be considered a risk factor for CSR or RVO by the ophthalmologist

• Patients who have neuromuscular disorders that are associated with elevated CK

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of South Alabama / Mitchell Cancer Institute Univ South Alabama	Mobile	Alabama	United States	36688
2	Alaska Oncology and Hematology AOH (2)	Anchorage	Alaska	United States	99508
3	Arizona Oncology Associates AZ Oncology Assoc.	Phoenix	Arizona	United States
4	Arizona Oncology Associates HOPE Division	Phoenix	Arizona	United States
5	Arizona Oncology Associates PC- NAHOA	Sedona	Arizona	United States	86336
6	Highlands Oncology Group Highlands Oncology Group (22)	Fayetteville	Arkansas	United States	72703
7	PCR Oncology	Pismo Beach	California	United States	93449
8	University of California Davis Cancer Center UC Davis Cancer (3)	Sacramento	California	United States	95817
9	Rocky Mountain Cancer Centers USOR	Boulder	Colorado	United States	80304
10	Yale University School of Medicine Yale Cancer Center	New Haven	Connecticut	United States	06511
11	Whittingham Cancer Center Norwalk Hospital	Norwalk	Connecticut	United States	06856
12	Eastern Connecticut Hematology & Oncology Associates Dept. of ECHO	Norwich	Connecticut	United States	06360
13	Hematology Oncology PC Stamford Hospital	Stamford	Connecticut	United States	06902
14	Florida Cancer Specialists Florida Cancer Specialists (31	Fort Myers	Florida	United States	33901
15	Memorial Cancer Institute Memorial Healthcare System	Hollywood	Florida	United States	33021
16	Cancer Specialists of North Florida	Jacksonville	Florida	United States	32256
17	Mt. Sinai Comprehensive Cancer Center	Miami Beach	Florida	United States	33140
18	Ocala Oncology Center Dept. of Ocala Oncology Center	Ocala	Florida	United States	34474
19	Cancer Centers of Florida PA Cancer Centers of FL-Orlando-4	Ocoee	Florida	United States
20	University Cancer & Blood Center, LLC	Athens	Georgia	United States	30607
21	Lurie Children's Hospital of Chicago Developmental Therapeutics	Chicago	Illinois	United States	60611
22	Oncology Specialists, SC Onc Specialists	Park Ridge	Illinois	United States	60068-0736
23	Illinois Cancer Care IL. Cancer Care	Peoria	Illinois	United States	61615-7828
24	Indiana University Indiana Univ. - Purdue Univ.	Indianapolis	Indiana	United States	46202
25	University of Iowa Hospitals & Clinics Regulatory Contact 2	Iowa City	Iowa	United States	52242
26	Maryland Oncology Hematology, P.A. Oncology Hematology	Rockville	Maryland	United States	20850
27	Cancer and Hematology Centers of West Michigan Dept. of Oncology	Grand Rapids	Michigan	United States	49546
28	Metro MN CCOP - Coon Rapids	Coon Rapids	Minnesota	United States	55433
29	Research Medical Center Research Med Center (2)	Kansas City	Missouri	United States	64132
30	Washington University School of Medicine Washington University (16)	Saint Louis	Missouri	United States	63110
31	Glacier View Research Institute - Cancer Oncology Dept	Kalispell	Montana	United States	59901
32	Comprehensive Cancer Centers of Nevada CCC of Nevada (21)	Las Vegas	Nevada	United States	89109
33	Cancer Institute of New Jersey CINJ	New Brunswick	New Jersey	United States	08901
34	New Mexico Cancer Care Alliance Oncology Dept	Albuquerque	New Mexico	United States	87106
35	New York Oncology Hematology, P.C. NYOH Latham	Troy	New York	United States	12180
36	University of North Carolina Chapel Hill Physician Office Building	Chapel Hill	North Carolina	United States	27514
37	Duke University Medical Center Seeley G. Mudd Bldg.	Durham	North Carolina	United States	27710
38	Sanford Research/USD-Fargo Sanford Hematology Oncology	Fargo	North Dakota	United States	58122
39	Cleveland Clinic Foundation Cleveland Clinic (19)	Cleveland	Ohio	United States	44195
40	Ohio State University Medical Center Comprehensive Cancer Center	Columbus	Ohio	United States	43221
41	St. Charles Cancer Center	Bend	Oregon	United States	97701
42	Willamette Valley Clinical Studies Cancer Institute & Res. Ctr.	Eugene	Oregon	United States	97404
43	Northwest Cancer Specialists Vancouver Cancer Center	Portland	Oregon	United States	97210
44	Oregon Health & Science University Oregon Health & Science U (56)	Portland	Oregon	United States	97239
45	St. Luke's Hospital and Health Network St Luke's (2)	Bethlehem	Pennsylvania	United States
46	West Penn Allegheny Oncology Network	Natrona Heights	Pennsylvania	United States	15065
47	Abington Hematology Oncology Associates, Inc Abington Hem Onc Assoc (5)	Willow Grove	Pennsylvania	United States	19090
48	Chattanooga Oncology and Hematology Assoicates, PC Chattanooga Oncology	Chattanooga	Tennessee	United States	37404
49	The West Clinic Dept. of the West Clinic	Memphis	Tennessee	United States	38120
50	Sarah Cannon Research Institute Sarah Cannon Research Inst (51	Nashville	Tennessee	United States	37203
51	Texas Oncology Presbyterian Hospital (3)	Dallas	Texas	United States	75246
52	Texas Oncology Texas Oncology - Denton	Dallas	Texas	United States	75246
53	Texas Oncology Austin Midtown	Dallas	Texas	United States	75251
54	Texas Oncology Texas Oncology - Midland	Dallas	Texas	United States	75251
55	Sammons Cancer Center - Texas Oncology Sammons Cancer Center (10)	Dallas	Texas	United States	78246
56	Oncology Consultants Oncology Group	Houston	Texas	United States	77024
57	MD Anderson Cancer Center/University of Texas MD Anderson Cancer Center (3)	Houston	Texas	United States	77030
58	Cancer Care Centers of South Texas / HOAST CCC of So. TX-San Antonio (3)	San Antonio	Texas	United States	78229
59	Tyler Cancer Center Dept.ofTylerCancerCtr. (2)	Tyler	Texas	United States	75702
60	Deke Slayton Cancer Center Deke Slayton Cancer Center (2)	Webster	Texas	United States	77598
61	Intermountain Medical Center Intermountain Healthcare	Murray	Utah	United States	84157
62	Virginia Cancer Specialists, PC Virginia Cancer Specialists	Fairfax	Virginia	United States	22031
63	Medical Oncology & Hematology Associates of Northern VA Med Onc Hem Northern VA	Reston	Virginia	United States	20190
64	Kadlec Clinic Hematology and Oncology Kadlec Clinic Hematology & Onc	Kennewick	Washington	United States	99336
65	Providence Regional Cancer System	Lacey	Washington	United States	98503
66	MultiCare Health System Institute for Research & Innovation MultiCare	Tacoma	Washington	United States	98405
67	Northwest Medical Specialties NW Medical Specialties	Tacoma	Washington	United States	98405
68	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin	United States	53226

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT01885195
• Other Study ID Numbers: CMEK162AUS11; C4211007
• First Posted: Jun 24, 2013
• Last Update Posted: Feb 21, 2021
• Last Verified: Feb 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Pfizer: RAS, RAF, MEK, NF1, MEK162, signature, papillary thyroid, small intestine, bladder, esophagus, lung cancer, NSCLC, acute myelogenous leukemia, AML
• Additional relevant MeSH terms: Hematologic Neoplasms

Study Results

Participant Flow

Pre-assignment Detail	Participants diagnosed with select solid tumors or hematological malignancies pre-identified (prior to study consent) and had an activation of the v-raf murine sarcoma viral oncogene (RAF)/ RAS oncogene [rat sarcoma viral oncogene homologue] (RAS)/mitogen-activated erk kinase (MEK) pathway and whose disease had progressed on or after standard treatment.

Arm/Group Title	Binimetinib (MEK162)
Arm/Group Description	Participants received an oral dose of 45 milligram (mg) of binimetinib tablets (3 tablets of 15 mg) twice daily in each cycle starting from Cycle 1 Day 1 (1 cycle =28 days) until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment due to any other reason. Maximum treatment exposure was approximately of 19.4 months.
Period Title: Overall Study
STARTED	110
COMPLETED	0
NOT COMPLETED	110

Baseline Characteristics

Arm/Group Title	Binimetinib (MEK162)
Arm/Group Description	Participants received an oral dose of 45 mg of binimetinib tablets (3 tablets of 15 mg) twice daily in each cycle starting from Cycle 1 Day 1 (1 cycle =28 days) until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment due to any other reason. Maximum treatment exposure was approximately of 19.4 months.
Overall Participants	110
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	60.4 (12.29)
Sex: Female, Male (Count of Participants)
Female	68 61.8%
Male	42 38.2%

Outcome Measures

1. Primary Outcome

Title	Clinical Benefit Rate (CBR) for Solid Tumors at Week 16 as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Description	CBR: participants with complete response (CR), partial response (PR) or stable disease (SD) for at least 16 weeks. As per RECIST 1.1, CR: disappearance of all target and non-target lesions, normalization of tumor marker level, pathological lymph nodes assigned as target or non-target lesions must have a reduction in short axis to less than (<) 10 millimeter (mm); PR: at least a 30 percent (%) decrease in sum of diameter of all target lesions, taking as reference the baseline sum of diameters; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters; PD: at least a 20% increase in sum of diameter of all measured target lesions, taking as reference smallest sum of diameter of all target lesions recorded at or after baseline, sum was also an absolute increase of at least 5 mm. Unequivocal progression of existing non-target lesions. Appearance of >=1 new target or non-target lesions.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

Full analysis set included all the participants who had received at least 1 dose of study drug. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

Arm/Group Title	Binimetinib (MEK162)
Arm/Group Description	Participants received an oral dose of 45 mg of binimetinib tablets (3 tablets of 15 mg) twice daily in each cycle starting from Cycle 1 Day 1 (1 cycle =28 days) until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment due to any other reason. Maximum treatment exposure was approximately of 19.4 months.
Measure Participants	104
Number (95% Confidence Interval) [Percentage of participants]	23.1 21%

2. Primary Outcome

Title	CBR for Hematologic Tumors at Week 16: Multiple Myeloma
Description	CBR: participants with stringent complete response(sCR), CR, very good partial response(VGPR), PR/SD for at least 16 weeks. For hematologic tumors (multiple myeloma), sCR: negative immunofixation on serum, urine, disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow plus normal free light chain(FLC) ratio and absence of clonal cells in bone marrow by immunohistochemistry/immunofluorescence; CR: negative immunofixation on the serum, urine, disappearance of any soft tissue, plasmacytomas and <5% plasma cells in bone marrow; VGPR: serum,urine M-component detectable by immunofixation but not on electrophoresis or>=90% reduction in serum M-component plus urine M-component <100 mg/24 hr; PR: >50% reduction of serum M-protein and reduction in 24hr urinary M-protein by >90%/to <200 mg/24 hr; SD: not meeting criteria for CR, VGPR, PRor PD; PD: increase of >25% from lowest response value in serum M-component, urine M-component and bone marrow plasma cell percentage.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

Full analysis set included all the participants who had received at least 1 dose of study drug. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

Arm/Group Title	Binimetinib (MEK162)
Arm/Group Description	Participants received an oral dose of 45 mg of binimetinib tablets (3 tablets of 15 mg) twice daily in each cycle starting from Cycle 1 Day 1 (1 cycle =28 days) until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment due to any other reason. Maximum treatment exposure was approximately of 19.4 months.
Measure Participants	3
Number (95% Confidence Interval) [Percentage of participants]	0.0 0%

3. Primary Outcome

Title	CBR for Hematologic Tumors at Week 16: Acute Myeloid Leukemia
Description	CBR: participants with complete remission (CR), CR with incomplete blood count recovery (CRi), partial remission (PR) and no resposne for at least 16 weeks. For hematologic tumors (acute myeloid leukemia); CR: as bone marrow- < 5% blasts, no blasts with auer rods, peripheral blood- neutrophils ≥1.0*10^9/L and/or platelets ≥100*10^9/L, ≤1% blasts, no evidence of extramedullary disease (such as CNS or soft tissue involvement), transfusion independent; CRi: all the CR criteria were involved but platelet and neutrophil transfusions were also allowed; PR: bone marrow- 50% or greater decrease (absolute range 5-25% blasts), < 5% of blasts contain auer rods, peripheral blood- neutrophils <1.0*10^9/L and/or platelets <100*10^9/L, no evidence of extramedullary disease; no response: in case a patient did not achieve CR, CRi, PR or relapse for an individual response assessment.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

Full analysis set included all the participants who had received at least 1 dose of study drug. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

Arm/Group Title	Binimetinib (MEK162)
Arm/Group Description	Participants received an oral dose of 45 mg of binimetinib tablets (3 tablets of 15 mg) twice daily in each cycle starting from Cycle 1 Day 1 (1 cycle =28 days) until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment due to any other reason. Maximum treatment exposure was approximately of 19.4 months.
Measure Participants	3
Number (95% Confidence Interval) [Percentage of participants]	33.3 30.3%

4. Secondary Outcome

Title	Overall Response Rate (ORR) as Per RECIST Version 1.1
Description	ORR: percentage of participants with a best overall response (BOR) of CR or PR as assessed per RECIST version 1.1. BOR: the best response recorded from the start of the treatment until disease progression (PD). CR: disappearance of all target and non-target lesions, normalization of tumor marker level, pathological lymph nodes assigned as target or non-target lesions must have a reduction in short axis to less than <10 mm; PR: at least a 30 % decrease in sum of diameter of all target lesions, taking as reference the baseline sum of diameters; PD: at least a 20% increase in sum of diameter of all measured target lesions, taking as reference smallest sum of diameter of all target lesions recorded at or after baseline, sum was also an absolute increase of at least 5 mm. Unequivocal progression of existing non-target lesions. Appearance of >=1 new target or non-target lesions.
Time Frame	From the start of the treatment until disease progression (maximum up to 19.4 months)

Outcome Measure Data

Analysis Population Description

Full analysis set included all the participants who had received at least 1 dose of study drug. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

Arm/Group Title	Binimetinib (MEK162)
Arm/Group Description	Participants received an oral dose of 45 mg of binimetinib tablets (3 tablets of 15 mg) twice daily in each cycle starting from Cycle 1 Day 1 (1 cycle =28 days) until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment due to any other reason. Maximum treatment exposure was approximately of 19.4 months.
Measure Participants	104
Number (95% Confidence Interval) [Percentage of participants]	2.9 2.6%

5. Secondary Outcome

Title	ORR for Hematologic Tumors: Multiple Myeloma
Description	ORR: percentage of participants with sCR, CR, VGPR or PR. For hematologic tumors (multiple myeloma), sCR: negative immunofixation on the serum, urine, disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow plus normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence; CR: CR: negative immunofixation on the serum, urine, disappearance of any soft tissue, plasmacytomas and <5% plasma cells in bone marrow; VGPR: serum and urine M-component detectable by immunofixation but not on electrophoresis or greater than equal to >=90% reduction in serum M-component plus urine M-component <100 mg per 24hour (hr); PR: >50% reduction of serum M-protein and reduction in 24 hr urinary M-protein by >90% or to <200 mg/24 hr.
Time Frame	From the start of the treatment until disease progression (maximum up to 19.4 months)

Outcome Measure Data

Analysis Population Description

Full analysis set included all the participants who had received at least 1 dose of study drug. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

Arm/Group Title	Binimetinib (MEK162)
Arm/Group Description	Participants received an oral dose of 45 mg of binimetinib tablets (3 tablets of 15 mg) twice daily in each cycle starting from Cycle 1 Day 1 (1 cycle =28 days) until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment due to any other reason. Maximum treatment exposure was approximately of 19.4 months.
Measure Participants	3
Number (95% Confidence Interval) [Percentage of participants]	33.3 30.3%

6. Secondary Outcome

Title	ORR for Hematologic Tumors: Acute Myeloid Leukemia
Description	ORR: participants with complete remission (CR), CR with incomplete blood count recovery (CRi), partial remission (PR) and no resposne for at least 16 weeks. For hematologic tumors (acute myeloid leukemia); CR: as bone marrow- < 5% blasts, no blasts with auer rods, peripheral blood- neutrophils ≥1.0*10^9/L and/or platelets ≥100*10^9/L, ≤1% blasts, no evidence of extramedullary disease (such as CNS or soft tissue involvement), transfusion independent; CRi: all the CR criteria were involved but platelet and neutrophil transfusions were also allowed; PR: bone marrow- 50% or greater decrease (absolute range 5-25% blasts), < 5% of blasts contain auer rods, peripheral blood- neutrophils <1.0*10^9/L and/or platelets <100*10^9/L, no evidence of extramedullary disease.
Time Frame	From the start of the treatment until disease progression (maximum up to 19.4 months)

Outcome Measure Data

Analysis Population Description

Full analysis set included all the participants who had received at least 1 dose of study drug. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

Arm/Group Title	Binimetinib (MEK162)
Arm/Group Description	Participants received an oral dose of 45 mg of binimetinib tablets (3 tablets of 15 mg) twice daily in each cycle starting from Cycle 1 Day 1 (1 cycle =28 days) until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment due to any other reason. Maximum treatment exposure was approximately of 19.4 months.
Measure Participants	3
Number (95% Confidence Interval) [Percentage of participants]	33.3 30.3%

7. Secondary Outcome

Title	Progression-free Survival (PFS) as Per RECIST Version 1.1
Description	PFS was defined as the time from the date of first dose to the date of first documented PD or relapse or death due to any cause. PD: at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of existing non-target lesions. Appearance of >=1 new target or non-target lesions was also considered progression. PFS data was censored at date of last adequate tumor assessment.
Time Frame	From the date of first dose to the date of the first documented PD, censored date or death (maximum up to 19.4 months)

Outcome Measure Data

Analysis Population Description

Full analysis set included all the participants who had received at least 1 dose of study drug.

Arm/Group Title	Binimetinib (MEK162)
Arm/Group Description	Participants received an oral dose of 45 mg of binimetinib tablets (3 tablets of 15 mg) twice daily in each cycle starting from Cycle 1 Day 1 (1 cycle =28 days) until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment due to any other reason. Maximum treatment exposure was approximately of 19.4 months.
Measure Participants	110
Median (95% Confidence Interval) [Months]	2.6

8. Secondary Outcome

Title	Overall Survival (OS)
Description	OS was defined as the time from the date of first dose to the date of death due to any cause. If a participant was not known to have died, survival time was censored at the date of last contact.
Time Frame	From the date of first dose to the date of death due to any cause (maximum up to 19.4 months)

Outcome Measure Data

Analysis Population Description

Full analysis set included all the participants who had received at least 1 dose of study drug.

Arm/Group Title	Binimetinib (MEK162)
Arm/Group Description	Participants received an oral dose of 45 mg of binimetinib tablets (3 tablets of 15 mg) twice daily in each cycle starting from Cycle 1 Day 1 (1 cycle =28 days) until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment due to any other reason. Maximum treatment exposure was approximately of 19.4 months.
Measure Participants	110
Median (95% Confidence Interval) [Months]	8.5

9. Secondary Outcome

Title	Duration of Response (DOR) as Per RECIST Version 1.1
Description	DOR was defined as the time from the first documented response (CR or PR) to the date of first documented disease progression, relapse or death due to any cause. As per RECIST 1.1, CR: disappearance of all target and non-target lesions, normalization of tumor marker level, pathological lymph nodes assigned as target or non-target lesions must have a reduction in short axis to <10 mm; PR: at least a 30% decrease in sum of diameter of all target lesions, taking as reference the baseline sum of diameters; PD: at least a 20% increase in sum of diameter of all measured target lesions, taking as reference smallest sum of diameter of all target lesions recorded at or after baseline, sum was also an absolute increase of at least 5 mm. Unequivocal progression of existing non-target lesions. Appearance of >=1 new target or non-target lesions. The DOR was determined only in participants whose best response was PR or greater.
Time Frame	From the first documented response (CR or PR) to the date of the first documented PD or death (maximum up to 19.4 months)

Outcome Measure Data

Analysis Population Description

Full analysis set included all the participants who had received at least 1 dose of study drug. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

Arm/Group Title	Binimetinib (MEK162)
Arm/Group Description	Participants received an oral dose of 45 mg of binimetinib tablets (3 tablets of 15 mg) twice daily in each cycle starting from Cycle 1 Day 1 (1 cycle =28 days) until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment due to any other reason. Maximum treatment exposure was approximately of 19.4 months.
Measure Participants	3
Median (95% Confidence Interval) [Months]	NA

10. Secondary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events (TEAEs) Graded According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03
Description	Adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated. Treatment-emergent adverse events were defined as new or worsening events that were collected from first study treatment date to last treatment date +30 days. AEs of all grades were reported.
Time Frame	From Baseline up to 30 days following the last dose of study treatment (maximum up to 21 months)

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of study treatment and had at least 1 post-baseline safety assessment.

Arm/Group Title	Binimetinib (MEK162)
Arm/Group Description	Participants received an oral dose of 45 mg of binimetinib tablets (3 tablets of 15 mg) twice daily in each cycle starting from Cycle 1 Day 1 (1 cycle =28 days) until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment due to any other reason. Maximum treatment exposure was approximately of 19.4 months.
Measure Participants	110
Grade 1	2 1.8%
Grade 2	27 24.5%
Grade 3	64 58.2%
Grade 4	17 15.5%

11. Secondary Outcome

Title	Number of Participants With Vital Sign Abnormality of Greater Than or Equal to (>=) Grade 3 as Per CTCAE v4.03
Description	Vital signs included hypertension, hypotension and weight decreased were reported. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated. Participants with grade 3 or higher vital sign abnormality are reported.
Time Frame	From Baseline up to 30 days following the last dose of study treatment (maximum up to 21 months)

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of study treatment and had at least 1 post-baseline safety assessment.

Arm/Group Title	Binimetinib (MEK162)
Arm/Group Description	Participants received an oral dose of 45 mg of binimetinib tablets (3 tablets of 15 mg) twice daily in each cycle starting from Cycle 1 Day 1 (1 cycle =28 days) until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment due to any other reason. Maximum treatment exposure was approximately of 19.4 months.
Measure Participants	110
Hypertension	15 13.6%
Hypotension	6 5.5%
Weight Decreased	11 10%

12. Secondary Outcome

Title	Number of Participants With Electrocardiogram (ECG) Abnormalities
Description	ECG abnormalities criteria included: 1) QTc interval adjusted according to Bazett formula (QTcF) in millisecond (msec): greater than equal to (>=) 450 to less than (<) 480, >=480 to <500, >=500, increase from baseline >=30, increase from baseline >=60; 2) QTc interval adjusted according to Fridericia formula (QTcB) (msec): >=450 to <480, >=480 to <500, >=500, increase from baseline >=30, increase from baseline >=60. 3) QT (msec): >=450 to <480, >=480 to <500, >=500, increase from baseline >=30, increase from baseline >=60.
Time Frame	From Baseline up to 30 days following the last dose of study treatment (maximum up to 21 months)

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of study treatment and had at least 1 post-baseline safety assessment.

Arm/Group Title	Binimetinib (MEK162)
Arm/Group Description	Participants received an oral dose of 45 mg of binimetinib tablets (3 tablets of 15 mg) twice daily in each cycle starting from Cycle 1 Day 1 (1 cycle =28 days) until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment due to any other reason. Maximum treatment exposure was approximately of 19.4 months.
Measure Participants	110
QTcF: >=450 to <480 msec	15 13.6%
QTcF: >=480 to <500 msec	4 3.6%
QTcF: >=500 msec	1 0.9%
QTcF: Increase from baseline >=30 msec	20 18.2%
QTcF: Increase from baseline >=60 msec	3 2.7%
QTcB: >=450 to <480 msec	13 11.8%
QTcB: >=480 to <500 msec	5 4.5%
QTcB: >=500 msec	8 7.3%
QTcB: Increase from baseline >=30 msec	53 48.2%
QTcB: Increase from baseline >=60 msec	29 26.4%
QT: >=450 to <480 msec	13 11.8%
QT: >=480 to <500 msec	2 1.8%
QT: >=500 msec	2 1.8%
QT: Increase from baseline >=30 msec	39 35.5%
QT: Increase from baseline >=60 msec	7 6.4%

13. Secondary Outcome

Title	Number of Participants With Shift From Baseline in Clinical Laboratory - Hematology Parameters
Description	Laboratory parameters included hematological and biochemistry parameters. Hematological parameters included neutrophils, platelets, prothrombin time, activated partial thromboplastin time, INR, fibrinogen. Number of participants with hematological abnormalities by grades (as per Common Terminology Criteria for Adverse Events (CTCAE version 4.03) were reported. Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Participants with a grade shift of 3 or more from baseline are reported in this outcome measure.
Time Frame	From Baseline up to 30 days following the last dose of study treatment (maximum up to 21 months)

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of study treatment and had at least 1 post-baseline safety assessment. Here, "Number Analyzed" signifies number of participants evaluable for specified rows.

Arm/Group Title	Binimetinib (MEK162)
Arm/Group Description	Participants received an oral dose of 45 mg of binimetinib tablets (3 tablets of 15 mg) twice daily in each cycle starting from Cycle 1 Day 1 (1 cycle =28 days) until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment due to any other reason. Maximum treatment exposure was approximately of 19.4 months.
Measure Participants	110
Neutrophils	6 5.5%
Platelets	3 2.7%
Prothrombin Time	2 1.8%
Activated Partial Thromboplastin Time	2 1.8%
INR	2 1.8%
Fibrinogen	0 0%

14. Secondary Outcome

Title	Number of Participants With Shift From Baseline in Clinical Laboratory - Biochemistry Parameters
Description	Laboratory parameters included hematological and biochemistry parameters. Biochemistry parameters included: creatinine, phosphorus, albumin, gamma-glutamyl transferase, aspartate transaminase, alanine aminotransferase, alkaline phosphatase, total bilirubin, uric acid, amylase, lipase, creatine kinase, total cholesterol and triglycerides. Number of participants with biochemistry test abnormalities by grades (CTCAE version 4.03) were reported. Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Participants with a grade shift of 3 or more from baseline are reported in this outcome measure.
Time Frame	From Baseline up to 30 days following the last dose of study treatment (maximum up to 21 months)

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of study treatment and had at least 1 post-baseline safety assessment. Here, "Number Analyzed" signifies number of participants evaluable for specified rows.

Arm/Group Title	Binimetinib (MEK162)
Arm/Group Description	Participants received an oral dose of 45 mg of binimetinib tablets (3 tablets of 15 mg) twice daily in each cycle starting from Cycle 1 Day 1 (1 cycle =28 days) until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment due to any other reason. Maximum treatment exposure was approximately of 19.4 months.
Measure Participants	110
Creatinine	0 0%
Phosphorus	1 0.9%
Albumin	5 4.5%
Gamma-Glutamyl Transferase	1 0.9%
Aspartate Transaminase	2 1.8%
Alanine Aminotransferase	2 1.8%
Alkaline Phosphatase	0 0%
Total Bilirubin	0 0%
Uric Acid	0 0%
Amylase	2 1.8%
Lipase	5 4.5%
Creatine Kinase	18 16.4%
Total Cholesterol	0 0%
Triglycerides	1 0.9%

15. Secondary Outcome

Title	Number of Participants With Shift From Baseline in Cardiac Imaging
Description	Number of Participants With Shift From Baseline in Cardiac Imaging were reported.
Time Frame	From Baseline up to 30 days following the last dose of study treatment (maximum up to 21 months)

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of study treatment and had at least 1 post-baseline safety assessment.

Arm/Group Title	Binimetinib (MEK162)
Arm/Group Description	Participants received an oral dose of 45 mg of binimetinib tablets (3 tablets of 15 mg) twice daily in each cycle starting from Cycle 1 Day 1 (1 cycle =28 days) until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment due to any other reason. Maximum treatment exposure was approximately of 19.4 months.
Measure Participants	110
Count of Participants [Participants]	10 9.1%

Adverse Events

Time Frame	From Baseline up to 30 days following the last dose of study treatment (maximum up to 21 months)
Adverse Event Reporting Description	Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Safety analysis set included all the participants who received at least 1 dose of study treatment and had at least 1 post-baseline safety assessment.
Arm/Group Title	Binimetinib (MEK162)
Arm/Group Description	Participants received an oral dose of 45 mg of binimetinib tablets (3 tablets of 15 mg) twice daily in each cycle starting from Cycle 1 Day 1 (1 cycle =28 days) until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment due to any other reason. Maximum treatment exposure was approximately of 19.4 months.
All Cause Mortality
	Binimetinib (MEK162)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Binimetinib (MEK162)
	Affected / at Risk (%)	# Events
Total	50/110 (45.5%)
Blood and lymphatic system disorders
Coagulopathy	1/110 (0.9%)
Febrile neutropenia	1/110 (0.9%)
Cardiac disorders
Dilatation ventricular	1/110 (0.9%)
Eye disorders
Cataract	1/110 (0.9%)
Retinal artery occlusion	1/110 (0.9%)
Retinal detachment	1/110 (0.9%)
Retinal tear	1/110 (0.9%)
Vitreous haemorrhage	1/110 (0.9%)
Gastrointestinal disorders
Abdominal pain	4/110 (3.6%)
Small intestinal obstruction	4/110 (3.6%)
Vomiting	2/110 (1.8%)
Ascites	1/110 (0.9%)
Diarrhoea	1/110 (0.9%)
Gastric ulcer	1/110 (0.9%)
Haematemesis	1/110 (0.9%)
Intestinal obstruction	1/110 (0.9%)
Mesenteric vein thrombosis	1/110 (0.9%)
Nausea	1/110 (0.9%)
Oesophageal haemorrhage	1/110 (0.9%)
Oesophageal obstruction	1/110 (0.9%)
Oesophageal perforation	1/110 (0.9%)
Pancreatitis	1/110 (0.9%)
Upper gastrointestinal haemorrhage	1/110 (0.9%)
General disorders
Oedema peripheral	2/110 (1.8%)
Asthenia	1/110 (0.9%)
Chest pain	1/110 (0.9%)
Fatigue	1/110 (0.9%)
Oedema	1/110 (0.9%)
Pain	1/110 (0.9%)
Pyrexia	2/110 (1.8%)
Hepatobiliary disorders
Bile duct obstruction	1/110 (0.9%)
Infections and infestations
Pneumonia	3/110 (2.7%)
Urinary tract infection	3/110 (2.7%)
Cellulitis	2/110 (1.8%)
Sepsis	2/110 (1.8%)
Cystitis	1/110 (0.9%)
Influenza	1/110 (0.9%)
Lung abscess	1/110 (0.9%)
Post procedural infection	1/110 (0.9%)
Streptococcal bacteraemia	1/110 (0.9%)
Upper respiratory tract infection	1/110 (0.9%)
Injury, poisoning and procedural complications
Femur fracture	1/110 (0.9%)
Hip fracture	1/110 (0.9%)
Investigations
Blood creatine phosphokinase increased	1/110 (0.9%)
Troponin I increased	1/110 (0.9%)
Troponin T increased	1/110 (0.9%)
Metabolism and nutrition disorders
Dehydration	4/110 (3.6%)
Decreased appetite	1/110 (0.9%)
Hypercalcaemia	1/110 (0.9%)
Musculoskeletal and connective tissue disorders
Back pain	1/110 (0.9%)
Musculoskeletal chest pain	1/110 (0.9%)
Myositis	1/110 (0.9%)
Pain in extremity	1/110 (0.9%)
Nervous system disorders
Haemorrhage intracranial	1/110 (0.9%)
Peripheral motor neuropathy	1/110 (0.9%)
Peripheral sensory neuropathy	1/110 (0.9%)
Psychiatric disorders
Confusional state	1/110 (0.9%)
Renal and urinary disorders
Urinary retention	1/110 (0.9%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	12/110 (10.9%)
Hypoxia	3/110 (2.7%)
Haemoptysis	2/110 (1.8%)
Pleural effusion	2/110 (1.8%)
Pulmonary embolism	2/110 (1.8%)
Chronic obstructive pulmonary disease	1/110 (0.9%)
Cough	1/110 (0.9%)
Pharyngeal oedema	1/110 (0.9%)
Pulmonary hypertension	1/110 (0.9%)
Respiratory distress	1/110 (0.9%)
Sleep apnoea syndrome	1/110 (0.9%)
Upper airway obstruction	1/110 (0.9%)
Vascular disorders
Embolism	1/110 (0.9%)
Haemorrhage	1/110 (0.9%)
Hypotension	1/110 (0.9%)
Lymphoedema	1/110 (0.9%)
Lymphorrhoea	1/110 (0.9%)
Other (Not Including Serious) Adverse Events
	Binimetinib (MEK162)
	Affected / at Risk (%)	# Events
Total	110/110 (100%)
Blood and lymphatic system disorders
Anaemia	29/110 (26.4%)
Neutropenia	7/110 (6.4%)
Eye disorders
Vision blurred	18/110 (16.4%)
Chorioretinopathy	8/110 (7.3%)
Periorbital oedema	7/110 (6.4%)
Visual impairment	6/110 (5.5%)
Gastrointestinal disorders
Diarrhoea	52/110 (47.3%)
Nausea	48/110 (43.6%)
Vomiting	42/110 (38.2%)
Constipation	25/110 (22.7%)
Dry mouth	11/110 (10%)
Dyspepsia	11/110 (10%)
Abdominal pain	10/110 (9.1%)
Stomatitis	9/110 (8.2%)
Ascites	6/110 (5.5%)
Dysphagia	6/110 (5.5%)
General disorders
Fatigue	55/110 (50%)
Oedema peripheral	44/110 (40%)
Mucosal inflammation	13/110 (11.8%)
Pyrexia	13/110 (11.8%)
Asthenia	11/110 (10%)
Face oedema	10/110 (9.1%)
Chills	7/110 (6.4%)
Oedema	7/110 (6.4%)
Infections and infestations
Urinary tract infection	19/110 (17.3%)
Investigations
Blood creatine phosphokinase increased	38/110 (34.5%)
Aspartate aminotransferase increased	22/110 (20%)
Alanine aminotransferase increased	15/110 (13.6%)
Lipase increased	13/110 (11.8%)
Amylase increased	11/110 (10%)
Blood lactate dehydrogenase increased	11/110 (10%)
Ejection fraction decreased	11/110 (10%)
Weight decreased	11/110 (10%)
Blood alkaline phosphatase increased	9/110 (8.2%)
Blood phosphorus increased	8/110 (7.3%)
Blood creatinine increased	6/110 (5.5%)
Gamma-glutamyltransferase increased	6/110 (5.5%)
Intraocular pressure increased	6/110 (5.5%)
Troponin T increased	6/110 (5.5%)
White blood cell count decreased	6/110 (5.5%)
Metabolism and nutrition disorders
Decreased appetite	24/110 (21.8%)
Hypomagnesaemia	17/110 (15.5%)
Hyperglycaemia	14/110 (12.7%)
Dehydration	11/110 (10%)
Hypokalaemia	11/110 (10%)
Hypoalbuminaemia	10/110 (9.1%)
Hyponatraemia	7/110 (6.4%)
Hyperkalaemia	6/110 (5.5%)
Musculoskeletal and connective tissue disorders
Muscular weakness	14/110 (12.7%)
Back pain	10/110 (9.1%)
Pain in extremity	8/110 (7.3%)
Myalgia	7/110 (6.4%)
Arthralgia	6/110 (5.5%)
Nervous system disorders
Dizziness	13/110 (11.8%)
Headache	7/110 (6.4%)
Neuropathy peripheral	6/110 (5.5%)
Psychiatric disorders
Insomnia	10/110 (9.1%)
Anxiety	9/110 (8.2%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	29/110 (26.4%)
Cough	15/110 (13.6%)
Epistaxis	6/110 (5.5%)
Pleural effusion	6/110 (5.5%)
Skin and subcutaneous tissue disorders
Rash	48/110 (43.6%)
Dermatitis acneiform	21/110 (19.1%)
Dry skin	15/110 (13.6%)
Pruritus	9/110 (8.2%)
Rash maculo-papular	8/110 (7.3%)
Vascular disorders
Hypertension	15/110 (13.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.