A Study of the Safety, Tolerability, and Effects of Cobim... | NCT02457793

NCT02457793

ID	Type	Description	Link
2015-000092-27	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

No data available

No data is available for this block.

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Not assigned	Experimental	One participant was assigned to receive intermittent cobimetinib 80 milligrams (mg) + GDC 0994 200 mg) and did receive study drug. However, the participant diary was not returned, and the site was unable to document study dose administration.	Drug: Cobimetinib Drug: GDC-0994
COB 20 mg + GDC 200 mg	Experimental	Concurrent or intermittent dosing of cobimetinib 20 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.	Drug: Cobimetinib Drug: GDC-0994
COB 40 mg + GDC 200 mg	Experimental	Concurrent or intermittent dosing of cobimetinib 40 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.	Drug: Cobimetinib Drug: GDC-0994
COB 80 mg + GDC 200 mg	Experimental	Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.	Drug: Cobimetinib Drug: GDC-0994
COB 80 mg + GDC 400 mg	Experimental	Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 400 mg for 21 consecutive days, followed by 7 days off.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Cobimetinib	Drug	Cobimetinib given concurrently or intermittently with GDC-0994 for 21 consecutive days followed by 7 days off.	COB 100 mg + GDC 200 mg COB 20 mg + GDC 200 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants With Dose-Limiting Toxicities (DLTs)	DLTs include symptoms considered by the investigator to be possibly related to study drug.	28 days (Cycle 1)
Percentage of Participants With at Least One Adverse Event	An adverse event is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution.	Up to 15 months
Percentage of Participants With at Least One Adverse Event of Special Interest	AESIs were graded per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v4.0. AESIs included the following: Grade ≥ 1 retinal vein occlusion; Grade ≥ 2 visual disturbances (including events suggestive of serous retinopathy); Grade ≥ 3 rash for > 7 days; Grade ≥ 3 diarrhea for > 3 days; Grade ≥ 2 left ventricular ejection fraction (LVEF) decrease; Grade 3 hepatotoxicity; any dose-limiting toxicity (DLT); cases of potential drug-induced liver injury that include an elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) (AST > 3 × baseline value [and above the upper limit of normal, ULN]) in combination with either an elevated bilirubin ( > 2 × ULN) or clinical jaundice; or suspected transmission of an infectious agent by either study drug.	Up to 15 months
Percentage of Participants With at Least One Serious Adverse Event (SAE)	A SAE is any experience that: results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is medically significant.	Up to 15 months
Percentage of Participants With Laboratory Abnormalities

Secondary Outcomes

Measure	Description	Time Frame
Maximum Serum Concentration (Cmax) for GDC-0994		Up to Day 22
Median Time to Maximum Serum Concentration (Tmax) for GDC-0994		Up to Day 22
Maximum Serum Concentration (Cmax) for Cobimetinib

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Histologically or cytologically documented, locally advanced or metastatic solid tumors for which standard therapy either does not exist or has proven ineffective or intolerable
Evaluable disease or disease measurable
Life expectancy > or = 12 weeks
Adequate hematologic and end organ function
For female patients of childbearing potential and male patients with partners of childbearing potential, use of an effective form of contraception with continued use for study duration and up to 3 months or more following discontinuation of treatment drug
Fluorodeoxyglucose positron emission tomography (FDG-PET) avid disease on baseline scan

For enrollment in part 2, patients must meet all of the following:

Measurable disease
No more than four prior systemic therapies for locally advanced or metastatic cancer

Exclusion Criteria:

History of prior significant toxicity from another MEK inhibitor or ERK inhibitor requiring discontinuation of treatment
Evidence of visible retinal pathology as assessed by ophthalmologic examination that is considered a risk factor for retinal vein thrombosis
History of glaucoma
Intraocular pressure > 21 mmHg as measured by tonometry
Predisposing factors to retinal vein occlusion (RVO)
History of RVO, neurosensory retinal detachment, or neovascular macular degeneration
Allergy or hypersensitivity to components of the cobimetinib or GDC-0994 formulation
Palliative radiotherapy within 2 weeks prior to first dose of study-drug treatment in Cycle 1
Experimental therapy within 4 weeks prior to first dose of study-drug treatment in Cycle 1
Major surgical procedure or significant traumatic injury within 4 weeks prior to the first dose of study-drug treatment in Cycle 1, or anticipation of the need for major surgery during the course of study treatment
Anti-cancer therapy within 28 days prior to the first dose of study-drug treatment in Cycle 1
Current severe, uncontrolled systemic disease
History of clinically significant cardiac dysfunction
History of symptomatic congestive heart failure or serious cardiac arrhythmia requiring treatment
History of myocardial infarction within 6 months prior to the first dose of study-drug treatment in Cycle 1
History of congenital long QT syndrome or QTc > 470 msec
LVEF
History of malabsorption or other condition that would interfere with enteral absorption
Clinically significant history of liver disease, current alcohol abuse, or current known active infection with HIV, hepatitis B virus, or hepatitis C virus
Any condition requiring warfarin or thrombolytic anticoagulants
Active autoimmune disease
Uncontrolled ascites requiring weekly large volume paracentesis for 3 consecutive weeks prior to enrollment
Pregnancy, lactation, or breastfeeding
Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms
No other history of or ongoing malignancy that would potentially interfere with the interpretation of the Pharmacodynamic (PD) or efficacy assays

Contacts/Locations Module

Name	Affiliation	Role
Clinical Trials	Genentech, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
University of Colorado		Aurora	Colorado	80045-2517	United States
Yale Cancer Center

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Not Assigned	One participant was assigned to receive intermittent cobimetinib 80 milligrams (mg) + GDC 0994 200 mg) and did receive study drug. However, the participant diary was not returned, and the site was unable to document study dose administration.
FG001	COB 20 mg + GDC 200 mg

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

COB 40 mg + GDC 200 mg

COB 80 mg + GDC 200 mg

COB 80 mg + GDC 400 mg

Laboratory abnormalities were graded per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v4.0.

SGPT/ALT - serum glutamic-pyruvic transaminase/alanine aminotransferase; SGOT/AST - serum glutamic oxaloacetic transaminase/aspartate aminotransferase

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Not Assigned	One participant was assigned to receive intermittent cobimetinib 80 milligrams (mg) + GDC 0994 200 mg) and did receive study drug. However, the participant diary was not returned, and the site was unable to document study dose administration.
BG001	COB 20 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 20 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
BG002	COB 40 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 40 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
BG003	COB 80 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
BG004	COB 80 mg + GDC 400 mg	Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 400 mg for 21 consecutive days, followed by 7 days off.
BG005	COB 100 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 100 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
BG006	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Dermatitis Acneiform

Title	Measurements
	OG0001 OG0010 OG0020 OG003

Primary

Percentage of Participants With at Least One Adverse Event

An adverse event is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution.

All participants.

Posted

Number

percentage of participants

Up to 15 months

ID	Title	Description
OG000	Not Assigned	One participant was assigned to receive intermittent cobimetinib 80 milligrams (mg) + GDC 0994 200 mg) and did receive study drug. However, the participant diary was not returned, and the site was unable to document study dose administration.
OG001	COB 20 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 20 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
OG002	COB 40 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 40 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
OG003	COB 80 mg + GDC 200 mg

Primary

Percentage of Participants With at Least One Adverse Event of Special Interest

AESIs were graded per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v4.0. AESIs included the following: Grade ≥ 1 retinal vein occlusion; Grade ≥ 2 visual disturbances (including events suggestive of serous retinopathy); Grade ≥ 3 rash for > 7 days; Grade ≥ 3 diarrhea for > 3 days; Grade ≥ 2 left ventricular ejection fraction (LVEF) decrease; Grade 3 hepatotoxicity; any dose-limiting toxicity (DLT); cases of potential drug-induced liver injury that include an elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) (AST > 3 × baseline value [and above the upper limit of normal, ULN]) in combination with either an elevated bilirubin ( > 2 × ULN) or clinical jaundice; or suspected transmission of an infectious agent by either study drug.

All participants.

Posted

Number

percentage of participants

Up to 15 months

ID	Title	Description
OG000	Not Assigned	One participant was assigned to receive intermittent cobimetinib 80 milligrams (mg) + GDC 0994 200 mg) and did receive study drug. However, the participant diary was not returned, and the site was unable to document study dose administration.
OG001	COB 20 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 20 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.

Primary

Percentage of Participants With at Least One Serious Adverse Event (SAE)

A SAE is any experience that: results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is medically significant.

All participants.

Posted

Number

percentage of participants

Up to 15 months

ID	Title	Description
OG000	Not Assigned	One participant was assigned to receive intermittent cobimetinib 80 milligrams (mg) + GDC 0994 200 mg) and did receive study drug. However, the participant diary was not returned, and the site was unable to document study dose administration.
OG001	COB 20 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 20 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
OG002	COB 40 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 40 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
OG003

Primary

Percentage of Participants With Laboratory Abnormalities

Laboratory abnormalities were graded per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v4.0.

SGPT/ALT - serum glutamic-pyruvic transaminase/alanine aminotransferase; SGOT/AST - serum glutamic oxaloacetic transaminase/aspartate aminotransferase

All participants. Data are reported for evaluable participants.

Posted

Number

percentage of participants

Up to 15 months

ID	Title	Description
OG000	Not Assigned	One participant was assigned to receive intermittent cobimetinib 80 milligrams (mg) + GDC 0994 200 mg) and did receive study drug. However, the participant diary was not returned, and the site was unable to document study dose administration.
OG001	COB 20 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 20 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
OG002	COB 40 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 40 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
OG003

Primary

Mean Change From Baseline in Diastolic Blood Pressure

All participants. Data are reported for evaluable participants.

Posted

Mean

Standard Deviation

millimeters of mercury (mmHg)

Baseline, up to 15 months

ID	Title	Description
OG000	Not Assigned	One participant was assigned to receive intermittent cobimetinib 80 milligrams (mg) + GDC 0994 200 mg) and did receive study drug. However, the participant diary was not returned, and the site was unable to document study dose administration.
OG001	COB 20 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 20 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
OG002	COB 40 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 40 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
OG003	COB 80 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.

Primary

Mean Change From Baseline in Lean Body Mass

All participants. Data are reported for evaluable participants.

Posted

Mean

Standard Deviation

kilograms (kg)

Baseline, Day 15

ID	Title	Description
OG000	Not Assigned	One participant was assigned to receive intermittent cobimetinib 80 milligrams (mg) + GDC 0994 200 mg) and did receive study drug. However, the participant diary was not returned, and the site was unable to document study dose administration.
OG001	COB 20 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 20 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
OG002	COB 40 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 40 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
OG003	COB 80 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.

Primary

Mean Change From Baseline in Pulse Rate

All participants. Data are reported for evaluable participants.

Posted

Mean

Standard Deviation

beats per minute

Baseline, up to 15 months

ID	Title	Description
OG000	Not Assigned	One participant was assigned to receive intermittent cobimetinib 80 milligrams (mg) + GDC 0994 200 mg) and did receive study drug. However, the participant diary was not returned, and the site was unable to document study dose administration.
OG001	COB 20 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 20 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
OG002	COB 40 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 40 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
OG003	COB 80 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.

Primary

Mean Change From Baseline in Respiratory Rate

All participants. Data are reported for evaluable participants.

Posted

Mean

Standard Deviation

breaths per minute

Baseline, up to 15 months

ID	Title	Description
OG000	Not Assigned	One participant was assigned to receive intermittent cobimetinib 80 milligrams (mg) + GDC 0994 200 mg) and did receive study drug. However, the participant diary was not returned, and the site was unable to document study dose administration.
OG001	COB 20 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 20 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
OG002	COB 40 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 40 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
OG003	COB 80 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.

Primary

Mean Change From Baseline in Systolic Blood Pressure

All participants. Data are reported for evaluable participants.

Posted

Mean

Standard Deviation

mmHg

Baseline, up to 15 months

ID	Title	Description
OG000	Not Assigned	One participant was assigned to receive intermittent cobimetinib 80 milligrams (mg) + GDC 0994 200 mg) and did receive study drug. However, the participant diary was not returned, and the site was unable to document study dose administration.
OG001	COB 20 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 20 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
OG002	COB 40 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 40 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
OG003	COB 80 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.

Primary

Mean Change From Baseline in Temperature

All participants. Data are reported for evaluable participants.

Posted

Mean

Standard Deviation

degrees Celsius

Baseline, up to 15 months

ID	Title	Description
OG000	Not Assigned	One participant was assigned to receive intermittent cobimetinib 80 milligrams (mg) + GDC 0994 200 mg) and did receive study drug. However, the participant diary was not returned, and the site was unable to document study dose administration.
OG001	COB 20 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 20 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
OG002	COB 40 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 40 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
OG003	COB 80 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.

Primary

Mean Change From Baseline in Weight

All participants. Data are reported for evaluable participants.

Posted

Mean

Standard Deviation

Baseline, up to 15 months

ID	Title	Description
OG000	Not Assigned	One participant was assigned to receive intermittent cobimetinib 80 milligrams (mg) + GDC 0994 200 mg) and did receive study drug. However, the participant diary was not returned, and the site was unable to document study dose administration.
OG001	COB 20 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 20 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
OG002	COB 40 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 40 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
OG003	COB 80 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.

Secondary

Maximum Serum Concentration (Cmax) for GDC-0994

Data are reported for evaluable participants.

Posted

Geometric Mean

Geometric Coefficient of Variation

micromoles

Up to Day 22

ID	Title	Description
OG000	COB 80 mg + GDC 300 mg	Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 300 mg for 21 consecutive days, followed by 7 days off.
OG001	COB 20 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 20 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
OG002	COB 40 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 40 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
OG003	COB 80 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
OG004

Secondary

Median Time to Maximum Serum Concentration (Tmax) for GDC-0994

Data are reported for evaluable participants.

Posted

Mean

Full Range

hours

Up to Day 22

ID	Title	Description
OG000	COB 80 mg + GDC 300 mg	Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 300 mg for 21 consecutive days, followed by 7 days off.
OG001	COB 20 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 20 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
OG002	COB 40 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 40 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
OG003	COB 80 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
OG004

Secondary

Maximum Serum Concentration (Cmax) for Cobimetinib

Data are reported for evaluable participants.

Posted

Geometric Mean

Geometric Coefficient of Variation

nanograms per milliliter (ng/mL)

Up to Day 22

ID	Title	Description
OG000	COB 80 mg + GDC 300 mg	Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 300 mg for 21 consecutive days, followed by 7 days off.
OG001	COB 20 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 20 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
OG002	COB 40 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 40 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
OG003	COB 80 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.

Secondary

Median Time to Maximum Serum Concentration (Tmax) for Cobimetinib

Data are reported for evaluable participants.

Posted

Median

Full Range

hours

Up to Day 22

ID	Title	Description
OG000	COB 80 mg + GDC 300 mg	Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 300 mg for 21 consecutive days, followed by 7 days off.
OG001	COB 20 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 20 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
OG002	COB 40 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 40 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
OG003	COB 80 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
OG004

Secondary

Total Exposure (AUC From Time 0 to 24 Hour After Dose) for GDC-0994

Data are reported for evaluable participants.

Posted

Geometric Mean

Geometric Coefficient of Variation

hr x microM

0 to 24 hours post-dose (Up to Day 22)

ID	Title	Description
OG000	COB 80 mg + GDC 300 mg	Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 300 mg for 21 consecutive days, followed by 7 days off.
OG001	COB 20 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 20 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
OG002	COB 40 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 40 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
OG003	COB 80 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.

Secondary

Total Exposure (AUC From Time 0 to 24 Hour After Dose) for Cobimetinib

Data are reported for evaluable participants.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng x hr/mL

0 to 24 hours post-dose (Up to Day 22)

ID	Title	Description
OG000	COB 80 mg + GDC 300 mg	Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 300 mg for 21 consecutive days, followed by 7 days off.
OG001	COB 20 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 20 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
OG002	COB 40 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 40 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
OG003	COB 80 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.

Secondary

Mean Accumulation Ratio

Data for this measure were not collected.

Posted

Pre-dose Day 1 Cycle 1, 2, 3, Day 18, 21 Cycle 1; post-dose 0.5, 1, 2, 3, 4, 6 hours Day 1, 18, 21 Cycle 1; Day 2, 15, 19, 22, Cycle 1

ID	Title	Description
OG000	Not Assigned	One participant was assigned to receive intermittent cobimetinib 80 milligrams (mg) + GDC 0994 200 mg) and did receive study drug. However, the participant diary was not returned, and the site was unable to document study dose administration.
OG001	COB 20 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 20 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
OG002	COB 40 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 40 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
OG003	COB 80 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.

Secondary

Mean Terminal Half-life (t1/2)

Data for this measure were not collected.

Posted

Up to day 22 of study

ID	Title	Description
OG000	Not Assigned	One participant was assigned to receive intermittent cobimetinib 80 milligrams (mg) + GDC 0994 200 mg) and did receive study drug. However, the participant diary was not returned, and the site was unable to document study dose administration.
OG001	COB 20 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 20 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
OG002	COB 40 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 40 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
OG003	COB 80 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
OG004

Secondary

Change From Baseline in Fluorodeoxyglucose Positron Emission Tomography (FDG-PET)

Data for this measure were not collected.

Posted

Baseline, Day 15

ID	Title	Description
OG000	Not Assigned	One participant was assigned to receive intermittent cobimetinib 80 milligrams (mg) + GDC 0994 200 mg) and did receive study drug. However, the participant diary was not returned, and the site was unable to document study dose administration.
OG001	COB 20 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 20 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
OG002	COB 40 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 40 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
OG003	COB 80 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.

Secondary

Change From Baseline in Tumor Tissue Biomarkers

Data for this measure were not collected.

Posted

Up to 15 months

ID	Title	Description
OG000	Not Assigned	One participant was assigned to receive intermittent cobimetinib 80 milligrams (mg) + GDC 0994 200 mg) and did receive study drug. However, the participant diary was not returned, and the site was unable to document study dose administration.
OG001	COB 20 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 20 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
OG002	COB 40 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 40 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
OG003	COB 80 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
OG004

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Not Assigned	One participant was assigned to receive intermittent cobimetinib 80 milligrams (mg) + GDC 0994 200 mg) and did receive study drug. However, the participant diary was not returned, and the site was unable to document study dose administration.	1	1	1	1
EG001	COB 20 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 20 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.	2	5	5	5
EG002	COB 40 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 40 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.	2	3	3	3
EG003	COB 80 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.	3	5	5	5
EG004	COB 80 mg + GDC 400 mg	Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 400 mg for 21 consecutive days, followed by 7 days off.	2	4	4	4
EG005	COB 100 mg + GDC 200 mg	Concurrent or intermittent dosing of cobimetinib 100 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.	4	6	6	6

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
DIARRHOEA	Gastrointestinal disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected3 at risk EG0030 events0 affected5 at risk EG0040 events0 affected4 at risk EG0051 events1 affected6 at risk
ABDOMINAL PAIN	Gastrointestinal disorders	19.1	Systematic Assessment	EG0001 events1 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
COLITIS	Gastrointestinal disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
CONSTIPATION	Gastrointestinal disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
DYSPHAGIA	Gastrointestinal disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
GASTRIC ULCER	Gastrointestinal disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected3 at risk EG003
GASTROINTESTINAL HAEMORRHAGE	Gastrointestinal disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
NAUSEA	Gastrointestinal disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
CHOLANGITIS INFECTIVE	Infections and infestations	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
CLOSTRIDIUM DIFFICILE COLITIS	Infections and infestations	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
KLEBSIELLA BACTERAEMIA	Infections and infestations	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
PNEUMONIA	Infections and infestations	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
PNEUMONIA VIRAL	Infections and infestations	19.1	Systematic Assessment	EG0001 events1 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
DISEASE PROGRESSION	General disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected3 at risk EG003
GAIT DISTURBANCE	General disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
OEDEMA PERIPHERAL	General disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
PYREXIA	General disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
DYSPNOEA	Respiratory, thoracic and mediastinal disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
HYPOXIA	Respiratory, thoracic and mediastinal disorders	19.1	Systematic Assessment	EG0001 events1 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
PULMONARY EMBOLISM	Respiratory, thoracic and mediastinal disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
ANAEMIA	Blood and lymphatic system disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected3 at risk EG003
MYOCARDIAL INFARCTION	Cardiac disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
DEHYDRATION	Metabolism and nutrition disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
ANAEMIA	Blood and lymphatic system disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0021 events1 affected3 at risk EG0031 events1 affected5 at risk EG0043 events2 affected4 at risk EG0051 events1 affected6 at risk
THROMBOCYTOPENIA	Blood and lymphatic system disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0022 events1 affected3 at risk EG003
ACUTE MYOCARDIAL INFARCTION	Cardiac disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected3 at risk EG003
LEFT VENTRICULAR DYSFUNCTION	Cardiac disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
SINUS BRADYCARDIA	Cardiac disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected3 at risk EG003
SINUS TACHYCARDIA	Cardiac disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected3 at risk EG003
TACHYCARDIA	Cardiac disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected3 at risk EG003
DYSACUSIS	Ear and labyrinth disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected3 at risk EG003
VERTIGO	Ear and labyrinth disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected3 at risk EG003
ADRENAL INSUFFICIENCY	Endocrine disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected3 at risk EG003
DETACHMENT OF RETINAL PIGMENT EPITHELIUM	Eye disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0012 events2 affected5 at risk EG0021 events1 affected3 at risk EG003
EYELID OEDEMA	Eye disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
PERIORBITAL OEDEMA	Eye disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected3 at risk EG003
PHOTOPHOBIA	Eye disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
VISION BLURRED	Eye disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0012 events2 affected5 at risk EG0021 events1 affected3 at risk EG003
VISUAL IMPAIRMENT	Eye disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
VITREOUS FLOATERS	Eye disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected3 at risk EG003
ABDOMINAL DISTENSION	Gastrointestinal disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
ABDOMINAL PAIN	Gastrointestinal disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected3 at risk EG003
ABDOMINAL PAIN LOWER	Gastrointestinal disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
ABDOMINAL PAIN UPPER	Gastrointestinal disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected3 at risk EG003
ASCITES	Gastrointestinal disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0021 events1 affected3 at risk EG003
COLITIS	Gastrointestinal disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
CONSTIPATION	Gastrointestinal disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected3 at risk EG003
DIARRHOEA	Gastrointestinal disorders	19.1	Systematic Assessment	EG0001 events1 affected1 at risk EG0015 events4 affected5 at risk EG0022 events2 affected3 at risk EG003
DRY MOUTH	Gastrointestinal disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected3 at risk EG003
DYSPEPSIA	Gastrointestinal disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected3 at risk EG003
DYSPHAGIA	Gastrointestinal disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
FLATULENCE	Gastrointestinal disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected3 at risk EG003
GASTROINTESTINAL HAEMORRHAGE	Gastrointestinal disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected3 at risk EG003
GASTROOESOPHAGEAL REFLUX DISEASE	Gastrointestinal disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
HAEMATOCHEZIA	Gastrointestinal disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0022 events2 affected3 at risk EG003
NAUSEA	Gastrointestinal disorders	19.1	Systematic Assessment	EG0002 events1 affected1 at risk EG0015 events5 affected5 at risk EG0022 events2 affected3 at risk EG003
SALIVARY GLAND ENLARGEMENT	Gastrointestinal disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected3 at risk EG003
VOMITING	Gastrointestinal disorders	19.1	Systematic Assessment	EG0001 events1 affected1 at risk EG0014 events3 affected5 at risk EG0021 events1 affected3 at risk EG003
ASTHENIA	General disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0013 events3 affected5 at risk EG0022 events2 affected3 at risk EG003
CHILLS	General disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected3 at risk EG003
FACE OEDEMA	General disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected3 at risk EG003
FATIGUE	General disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0014 events4 affected5 at risk EG0021 events1 affected3 at risk EG003
GENERALISED OEDEMA	General disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected3 at risk EG003
LOCALISED OEDEMA	General disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0022 events2 affected3 at risk EG003
NON-CARDIAC CHEST PAIN	General disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected3 at risk EG003
OEDEMA PERIPHERAL	General disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0013 events2 affected5 at risk EG0023 events1 affected3 at risk EG003
PERIPHERAL SWELLING	General disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected3 at risk EG003
PYREXIA	General disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0021 events1 affected3 at risk EG003
ATYPICAL PNEUMONIA	Infections and infestations	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
BRONCHITIS	Infections and infestations	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
CANDIDA INFECTION	Infections and infestations	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected3 at risk EG003
PNEUMONIA	Infections and infestations	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected3 at risk EG003
SEPSIS	Infections and infestations	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected3 at risk EG003
UPPER RESPIRATORY TRACT INFECTION	Infections and infestations	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected3 at risk EG003
VULVOVAGINAL MYCOTIC INFECTION	Infections and infestations	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
CONTUSION	Injury, poisoning and procedural complications	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
LACERATION	Injury, poisoning and procedural complications	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected3 at risk EG003
ALANINE AMINOTRANSFERASE INCREASED	Investigations	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0012 events1 affected5 at risk EG0020 events0 affected3 at risk EG003
ASPARTATE AMINOTRANSFERASE INCREASED	Investigations	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0013 events2 affected5 at risk EG0020 events0 affected3 at risk EG003
BLOOD ALBUMIN DECREASED	Investigations	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
BLOOD ALKALINE PHOSPHATASE INCREASED	Investigations	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0012 events2 affected5 at risk EG0020 events0 affected3 at risk EG003
BLOOD BILIRUBIN INCREASED	Investigations	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected3 at risk EG003
BLOOD LACTATE DEHYDROGENASE INCREASED	Investigations	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
BLOOD LACTIC ACID INCREASED	Investigations	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected3 at risk EG003
BLOOD UREA INCREASED	Investigations	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
EJECTION FRACTION DECREASED	Investigations	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0012 events2 affected5 at risk EG0020 events0 affected3 at risk EG003
GAMMA-GLUTAMYLTRANSFERASE INCREASED	Investigations	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0012 events1 affected5 at risk EG0020 events0 affected3 at risk EG003
PLATELET COUNT DECREASED	Investigations	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
PROTEIN TOTAL DECREASED	Investigations	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
TROPONIN INCREASED	Investigations	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected3 at risk EG003
WEIGHT DECREASED	Investigations	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0021 events1 affected3 at risk EG003
WHITE BLOOD CELL COUNT INCREASED	Investigations	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected3 at risk EG003
DECREASED APPETITE	Metabolism and nutrition disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0022 events2 affected3 at risk EG003
DEHYDRATION	Metabolism and nutrition disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0014 events3 affected5 at risk EG0023 events2 affected3 at risk EG003
HYPERKALAEMIA	Metabolism and nutrition disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
HYPOALBUMINAEMIA	Metabolism and nutrition disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
HYPOCALCAEMIA	Metabolism and nutrition disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0022 events1 affected3 at risk EG003
HYPOGLYCAEMIA	Metabolism and nutrition disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected3 at risk EG003
HYPOKALAEMIA	Metabolism and nutrition disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0022 events1 affected3 at risk EG003
HYPOMAGNESAEMIA	Metabolism and nutrition disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0022 events1 affected3 at risk EG003
HYPONATRAEMIA	Metabolism and nutrition disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
HYPOPHOSPHATAEMIA	Metabolism and nutrition disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected3 at risk EG003
HYPOVOLAEMIA	Metabolism and nutrition disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected3 at risk EG003
MALNUTRITION	Metabolism and nutrition disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected3 at risk EG003
ARTHRALGIA	Musculoskeletal and connective tissue disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected3 at risk EG003
BACK PAIN	Musculoskeletal and connective tissue disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
MUSCLE SPASMS	Musculoskeletal and connective tissue disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected3 at risk EG003
MUSCULAR WEAKNESS	Musculoskeletal and connective tissue disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected3 at risk EG003
MYALGIA	Musculoskeletal and connective tissue disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
PAIN IN EXTREMITY	Musculoskeletal and connective tissue disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected3 at risk EG003
ATAXIA	Nervous system disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected3 at risk EG003
BURNING SENSATION	Nervous system disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected3 at risk EG003
DIZZINESS	Nervous system disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0022 events2 affected3 at risk EG003
HEADACHE	Nervous system disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
HYPOAESTHESIA	Nervous system disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected3 at risk EG003
LETHARGY	Nervous system disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected3 at risk EG003
PRESYNCOPE	Nervous system disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0021 events1 affected3 at risk EG003
SOMNOLENCE	Nervous system disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected3 at risk EG003
SYNCOPE	Nervous system disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected3 at risk EG003
VISUAL FIELD DEFECT	Nervous system disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
CONFUSIONAL STATE	Psychiatric disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected3 at risk EG003
DELIRIUM	Psychiatric disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected3 at risk EG003
INSOMNIA	Psychiatric disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected3 at risk EG003
ACUTE KIDNEY INJURY	Renal and urinary disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected3 at risk EG003
DYSURIA	Renal and urinary disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected3 at risk EG003
HAEMATURIA	Renal and urinary disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected3 at risk EG003
URINARY RETENTION	Renal and urinary disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
ALVEOLAR LUNG DISEASE	Respiratory, thoracic and mediastinal disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected3 at risk EG003
COUGH	Respiratory, thoracic and mediastinal disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0012 events2 affected5 at risk EG0021 events1 affected3 at risk EG003
DYSPHONIA	Respiratory, thoracic and mediastinal disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
DYSPNOEA	Respiratory, thoracic and mediastinal disorders	19.1	Systematic Assessment	EG0001 events1 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected3 at risk EG003
EPISTAXIS	Respiratory, thoracic and mediastinal disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
PLEURAL EFFUSION	Respiratory, thoracic and mediastinal disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected3 at risk EG003
PNEUMONITIS	Respiratory, thoracic and mediastinal disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected3 at risk EG003
PULMONARY EMBOLISM	Respiratory, thoracic and mediastinal disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected3 at risk EG003
PULMONARY HYPERTENSION	Respiratory, thoracic and mediastinal disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected3 at risk EG003
PULMONARY OEDEMA	Respiratory, thoracic and mediastinal disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected3 at risk EG003
RHINORRHOEA	Respiratory, thoracic and mediastinal disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
SINUS CONGESTION	Respiratory, thoracic and mediastinal disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
TONSILLAR HYPERTROPHY	Respiratory, thoracic and mediastinal disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected3 at risk EG003
ALOPECIA	Skin and subcutaneous tissue disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected3 at risk EG003
DERMATITIS ACNEIFORM	Skin and subcutaneous tissue disorders	19.1	Systematic Assessment	EG0002 events1 affected1 at risk EG0013 events2 affected5 at risk EG0023 events2 affected3 at risk EG003
DRY SKIN	Skin and subcutaneous tissue disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
HYPERHIDROSIS	Skin and subcutaneous tissue disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected3 at risk EG003
NIGHT SWEATS	Skin and subcutaneous tissue disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected3 at risk EG003
PAIN OF SKIN	Skin and subcutaneous tissue disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
RASH	Skin and subcutaneous tissue disorders	19.1	Systematic Assessment	EG0002 events1 affected1 at risk EG0011 events1 affected5 at risk EG0021 events1 affected3 at risk EG003
RASH MACULAR	Skin and subcutaneous tissue disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
RASH MACULO-PAPULAR	Skin and subcutaneous tissue disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0020 events0 affected3 at risk EG003
RASH PRURITIC	Skin and subcutaneous tissue disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
SWELLING FACE	Skin and subcutaneous tissue disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003
DEEP VEIN THROMBOSIS	Vascular disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected5 at risk EG0021 events1 affected3 at risk EG003
HYPOTENSION	Vascular disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0021 events1 affected3 at risk EG003
THROMBOSIS	Vascular disorders	19.1	Systematic Assessment	EG0000 events0 affected1 at risk EG0010 events0 affected5 at risk EG0020 events0 affected3 at risk EG003

ID	Term
D002289	Carcinoma, Non-Small-Cell Lung
D015179	Colorectal Neoplasms
D009369	Neoplasms
D008545	Melanoma

Ancestor Terms

ID	Term
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms
D008175	Lung Neoplasms
D012142	Respiratory Tract Neoplasms
D013899	Thoracic Neoplasms
D009371	Neoplasms by Site
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D007414	Intestinal Neoplasms
D005770	Gastrointestinal Neoplasms
D004067	Digestive System Neoplasms
D004066	Digestive System Diseases
D005767	Gastrointestinal Diseases
D003108	Colonic Diseases
D007410	Intestinal Diseases
D012002	Rectal Diseases
D018358	Neuroendocrine Tumors
D017599	Neuroectodermal Tumors
D009373	Neoplasms, Germ Cell and Embryonal
D009370	Neoplasms by Histologic Type
D009380	Neoplasms, Nerve Tissue
D018326	Nevi and Melanomas
D012878	Skin Neoplasms
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases

ID	Term
C574276	cobimetinib
C000619637	ravoxertinib

Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.

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