A Study of Cobimetinib Plus Paclitaxel, Cobimetinib Plus... | NCT02322814

ID	Type	Description	Link
2014-002230-32	EudraCT Number

Label	Type	Description	Intervention Names
Cohort I: Cobimetinib, Paclitaxel	Experimental	Participants will receive a combination of cobimetinib plus paclitaxel in 28-day cycles until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.	Drug: Cobimetinib Drug: Paclitaxel
Cohort I: Placebo, Paclitaxel	Placebo Comparator	Participants will receive a combination of cobimetinib placebo plus paclitaxel in 28-day cycles until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.	Drug: Paclitaxel Drug: Placebo
Cohort II:Cobimetinib,Paclitaxel,Atezolizumab	Experimental	Participants will receive cobimetinib plus paclitaxel plus atezolizumab in 28-day cycles until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.	Drug: Cobimetinib Drug: Paclitaxel Drug: Atezolizumab
Cohort III: Cobimetinib, Nab-Paclitaxel, Atezolizumab	Experimental	Participants will receive cobimetinib plus nab-paclitaxel plus atezolizumab until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.	Drug: Cobimetinib Drug: Atezolizumab

Name	Type	Description	Arm Group Labels	Other Names
Cobimetinib	Drug	Cobimetinib will be administered orally at a dose of 60 milligrams (mg) per day, once a day, on Day 3 through Day 23 of each 28-day treatment cycle.	Cohort I: Cobimetinib, Paclitaxel

Measure	Description	Time Frame
Cohort I: Progression-Free Survival, as Determined by Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)	PFS was defined as the time from randomization to the first occurrence of disease progression or relapse, as determined by the investigator, using RECIST v1.1. As per RECIST v1.1, progressive disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (nadir), including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). The appearance of one or more new lesions is also considered progression.	Randomization up to disease progression or relapse, whichever occurs first (up to approximately 2 years)
Cohort II, III: Percentage of Participants With Confirmed Overall Response (OR) (Partial Response [PR] or Complete Response [CR]), as Determined by the Investigator Using RECIST v1.1	OR was defined as the rate of a PR or CR occurring after randomization and confirmed >=28 days later as determined by the investigator using RECIST v1.1. As per RECIST v1.1, CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to <10 mm. PR is defined as at least a 30% decrease in the sum of diameters of all target and new measurable lesions.	Randomization up to disease progression or relapse, whichever occurs first (up to approximately 5.25 years)

Measure	Description	Time Frame
Cohort I, II, III: Overall Survival (OS)	OS was defined as the time from randomization to death from any cause	Randomization up to death from any cause (up to approximately 6.5 years)
Cohort I: Percentage of Participants With Confirmed OR (PR or CR), as Determined by the Investigator Using RECIST v1.1

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Histologically confirmed estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and human epidermal growth factor 2 (HER2)-negative adenocarcinoma of the breast with measurable metastatic or locally advanced disease
Locally advanced disease must not be amenable to resection with curative intent
Measurable disease, according to RECIST, v1.1
Adequate hematologic and end organ function
Agreement to use highly effective contraceptive methods as stated in protocol

Exclusion Criteria:

Disease-Specific Exclusion Criteria

Known HER2-, ER-positive, or PR-positive breast cancer by local laboratory assessment
Any prior chemotherapy, hormonal, or targeted therapy, for inoperable locally advanced or metastatic triple-negative breast cancer (mTNBC)
Any systemic anticancer therapy within 3 weeks prior to Cycle 1, Day 1
Any radiation treatment to metastatic site within 28 days of Cycle 1, Day 1
Major surgical procedure, open biopsy, or significant traumatic injury within 30 days prior to Cycle 1, Day 1 or anticipation of need for major surgical procedure during the course of the study
Prior exposure to experimental treatment targeting rapidly accelerated fibrosarcoma (Raf), MAP kinase/ERK kinase (MEK), or the mitogen-activated protein kinase (MAPK) pathway
Brain metastases (symptomatic or nonsymptomatic) that have not been treated previously, are progressive, or require any type of therapy (e.g., radiation, surgery, or steroids) to control symptoms from brain metastases within 30 days prior to first study treatment dose

Cobimetinib-Specific Exclusion Criteria

History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment/central serous chorioretinopathy (CSCR), retinal vein occlusion (RVO), or neovascular macular degeneration
Cobimetinib is metabolized by the hepatic cytochrome P3A4 (CYP3A4) enzyme. Drugs CYP3A4/5 inhibitors and inducers should be avoided

Atezolizumab-Specific Exclusion Criteria (Cohorts II and III Only)

History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
History of autoimmune disease
Prior allogenic stem cell or solid organ transplantation
History of idiopathic pulmonary fibrosis (including pneumonitis), drug induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest computed tomography (CT) scan
Positive test for Human Immunodeficiency Virus (HIV)
Active hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] or positive hepatitis B virus [HBV] deoxyribonucleic acid [DNA] test at screening) or hepatitis C
Active tuberculosis
Receipt of a live, attenuated vaccine within 4 weeks prior to randomization or anticipation that such a live, attenuated vaccine will be required during the study
Prior treatment with cluster of differentiation (CD) 137 (CD137) agonists or immune checkpoint blockade therapies, including anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4), anti-programmed death-1 (anti-PD-1), or anti-programmed death ligand-1 (anti-PD-L1) therapeutic antibodies
Treatment with systemic immunostimulatory agents (including but not limited to interferons or Interlukin-2 [IL-2]) within 4 weeks or five half-lives of the drug (whichever is shorter) prior to randomization
Treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to randomization, or anticipated requirement for systemic immunosuppressive medications during the trial

Cardiac Exclusion Criteria

History of clinically significant cardiac dysfunction
Corrected QT interval at screening greater than (>) 480 milliseconds (ms) (average of triplicate screening measurements)
Left ventricular ejection fraction (LVEF) below the institutional lower limit of normal or below 50 percent (%), whichever is lower

General Exclusion Criteria

No other history of or ongoing malignancy that would potentially interfere with the interpretation of the pharmacodynamic or efficacy assay
Pregnancy (positive serum pregnancy test) or lactation
Uncontrolled serious medical or psychiatric illness
Active infection requiring IV antibiotics on Cycle 1, Day 1
Participants who have a history of hypersensitivity reactions to paclitaxel or other drugs formulated in Cremophor® EL (polyoxyethylated castor oil) or to nab-paclitaxel and any of the excipients

Name	Affiliation	Role
Clinical Trials	Hoffmann-La Roche	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Cancer Specialists of North Florida		Jacksonville	Florida	32256-6932	United States
Mercy Hospital, a Campus of Plantation General Hospital

PubMed Identifier	Type	Citation	Retractions
36310331	Derived	Barteselli G, Goodman GR, Patel Y, Caro I, Xue C, McCallum S. Characterization of Serous Retinopathy Associated with Cobimetinib: Integrated Safety Analysis of Four Studies. Drug Saf. 2022 Dec;45(12):1491-1499. doi: 10.1007/s40264-022-01248-2. Epub 2022 Oct 30.

ID	Title	Description
FG000	Cohort I: Safety Run-In	Participants received cobimetinib plus paclitaxel until 12 participants completed one cycle of study treatment (28 days).
FG001	Cohort I: Placebo, Paclitaxel

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Oct 25, 2018

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Cohort I: Progression-Free Survival, as Determined by Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

PFS was defined as the time from randomization to the first occurrence of disease progression or relapse, as determined by the investigator, using RECIST v1.1. As per RECIST v1.1, progressive disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (nadir), including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). The appearance of one or more new lesions is also considered progression.

ITT population was defined as all enrolled participants, whether or not the assigned study treatment was received. Data were only collected from participants in the Cohort I Expansion Stage (Cohort I: Cobimetinib, Paclitaxel, Cohort I: Placebo, Paclitaxel) for this outcome measure.

Posted

Median

95% Confidence Interval

Weeks

Randomization up to disease progression or relapse, whichever occurs first (up to approximately 2 years)

ID	Title	Description
OG000	Cohort I: Cobimetinib, Paclitaxel	Participants received a combination of cobimetinib plus paclitaxel in 28-day cycles until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.
OG001	Cohort I: Placebo, Paclitaxel	Participants received a combination of cobimetinib placebo plus paclitaxel in 28-day cycles until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.

Units	Counts
Participants	OG00047 OG00143

Title

Denominators

Categories

Title	Measurements
	OG00023.71(18.14 to 32.14) OG00116.43(8.14 to 31.14)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Log Rank		0.2470		Hazard Ratio (HR)	0.73				95	0.43	1.24					Superiority

Primary

Cohort II, III: Percentage of Participants With Confirmed Overall Response (OR) (Partial Response [PR] or Complete Response [CR]), as Determined by the Investigator Using RECIST v1.1

OR was defined as the rate of a PR or CR occurring after randomization and confirmed >=28 days later as determined by the investigator using RECIST v1.1. As per RECIST v1.1, CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to <10 mm. PR is defined as at least a 30% decrease in the sum of diameters of all target and new measurable lesions.

ITT population was defined as all enrolled participants, whether or not the assigned study treatment was received.

Posted

Number

Percentage of participants

Randomization up to disease progression or relapse, whichever occurs first (up to approximately 5.25 years)

ID	Title	Description
OG000	Cohort II:Cobimetinib,Paclitaxel,Atezolizumab	Participants received cobimetinib plus paclitaxel plus atezolizumab in 28-day cycles until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.
OG001	Cohort III: Cobimetinib, Nab-Paclitaxel, Atezolizumab	Participants received cobimetinib plus nab-paclitaxel plus atezolizumab until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.

Secondary

Cohort I, II, III: Overall Survival (OS)

OS was defined as the time from randomization to death from any cause

Posted

Median

95% Confidence Interval

Months

Randomization up to death from any cause (up to approximately 6.5 years)

ID	Title	Description
OG000	Cohort I: Cobimetinib, Paclitaxel	Participants received a combination of cobimetinib plus paclitaxel in 28-day cycles until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.
OG001	Cohort I: Placebo, Paclitaxel	Participants received a combination of cobimetinib placebo plus paclitaxel in 28-day cycles until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.
OG002	Cohort II:Cobimetinib,Paclitaxel,Atezolizumab	Participants received cobimetinib plus paclitaxel plus atezolizumab in 28-day cycles until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.

Secondary

Cohort I: Percentage of Participants With Confirmed OR (PR or CR), as Determined by the Investigator Using RECIST v1.1

Posted

Number

Percentage of participants

Randomization up to disease progression or relapse, whichever occurs first (up to approximately 2 years)

ID	Title	Description
OG000	Cohort I: Cobimetinib, Paclitaxel	Participants received a combination of cobimetinib plus paclitaxel in 28-day cycles until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.
OG001	Cohort I: Placebo, Paclitaxel	Participants received a combination of cobimetinib placebo plus paclitaxel in 28-day cycles until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.

Secondary

Cohort I, II, III: Duration of Response (DOR), as Determined by the Investigator Using RECIST v1.1

DOR was defined as the time from the first occurrence of a documented objective response to the time of relapse, as determined by the investigator using RECIST v1.1 or death from any cause during the study, whichever occurred first.

ITT population was defined as all enrolled participants, whether or not the assigned study treatment was received.

Posted

Median

95% Confidence Interval

Months

Time from the first occurrence of documented objective response to time of relapse or death, whichever occurs first (up to approximately 6.5 years)

ID	Title	Description
OG000	Cohort I: Safety Run-In	Participants received cobimetinib plus paclitaxel until 12 participants completed one cycle of study treatment (28 days).
OG001	Cohort I: Cobimetinib, Paclitaxel	Participants received a combination of cobimetinib plus paclitaxel in 28-day cycles until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.
OG002	Cohort I: Placebo, Paclitaxel	Participants received a combination of cobimetinib placebo plus paclitaxel in 28-day cycles until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.

Secondary

Cohort I, II, III: Percentage of Participants With Unconfirmed Overall Response (OR_uc) (Unconfirmed PR or CR), as Determined by the Investigator Using RECIST v1.1

ORR_uc (ORR confirmation not required) was defined as the rate of a PR or CR occurring after randomization as determined by the investigator using RECIST v1.1, confirmation not required. As per RECIST v1.1, CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to <10 mm. PR is defined as at least a 30% decrease in the sum of diameters of all target and new measurable lesions.

Posted

Number

Percentage of participants

Randomization up to disease progression or relapse, whichever occurs fist (up to approximately 6.5 years)

ID	Title	Description
OG000	Cohort I: Cobimetinib, Paclitaxel	Participants received a combination of cobimetinib plus paclitaxel in 28-day cycles until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.
OG001	Cohort I: Placebo, Paclitaxel	Participants received a combination of cobimetinib placebo plus paclitaxel in 28-day cycles until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.

Secondary

Cohort II, III: Progression-Free Survival, as Determined by Investigator Using RECIST v1.1

PFS was defined as the time from randomization to the first occurrence of disease progression or relapse, as determined by the investigator, using RECIST v1.1. As per RECIST v1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (nadir), including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.

ITT population was defined as all enrolled participants, whether or not the assigned study treatment was received.

Posted

Median

95% Confidence Interval

Months

Randomization up to disease progression or relapse, whichever occurs first (up to approximately 6.5 years)

ID	Title	Description
OG000	Cohort II:Cobimetinib,Paclitaxel,Atezolizumab	Participants received cobimetinib plus paclitaxel plus atezolizumab in 28-day cycles until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.
OG001	Cohort III: Cobimetinib, Nab-Paclitaxel, Atezolizumab	Participants received cobimetinib plus nab-paclitaxel plus atezolizumab until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.

Secondary

Cohort I, II, III: Percentage of Participants With Adverse Events (AEs)

Safety-evaluable population was defined as participants who received any amount of any study drug.

Posted

Count of Participants

Participants

Randomization up to end of study (up to approximately 6.5 years)

ID	Title	Description
OG000	Cohort I: Safety Run-In	Participants received cobimetinib plus paclitaxel until 12 participants completed one cycle of study treatment (28 days).
OG001	Cohort I: Cobimetinib, Paclitaxel	Participants received a combination of cobimetinib plus paclitaxel in 28-day cycles until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.
OG002	Cohort I: Placebo, Paclitaxel	Participants received a combination of cobimetinib placebo plus paclitaxel in 28-day cycles until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.
OG003	Cohort II:Cobimetinib,Paclitaxel,Atezolizumab

Secondary

Cohort I, II, III: Maximum Plasma Concentration (Cmax) of Cobimetinib

The pharmacokinetic (PK) population included all participants with evaluable PK data who received at least one dose of study drug

Posted

Geometric Mean

Geometric Coefficient of Variation

Nanograms per millilitre (ng/mL)

Safety Run-In: Predose (Hour [Hr] 0) on Cycle (Cy) 1 Day (D) 8; predose (Hr 0), 0.5, 1, 2, 4, 6 Hr postdose (2, 4 Hr postdose for Cohorts II, III) on Cy1 D15; Expansion: predose (Hr 0), 1-4 Hr postdose on Cy1 D15; predose (Hr 0) on Cy2 D15 (Cy=28 days)

ID	Title	Description
OG000	Cohort I: Safety Run-In	Participants received cobimetinib plus paclitaxel until 12 participants completed one cycle of study treatment (28 days).
OG001	Cohort I: Cobimetinib, Paclitaxel	Participants received a combination of cobimetinib plus paclitaxel in 28-day cycles until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.
OG002	Cohort II:Cobimetinib,Paclitaxel,Atezolizumab	Participants received cobimetinib plus paclitaxel plus atezolizumab in 28-day cycles until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.

Secondary

Cohort I, II, III: Minimum Plasma Concentration (Cmin) of Cobimetinib

The PK population included all participants with evaluable PK data who received at least one dose of study drug

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Safety Run-In: Predose (Hr 0) on Cy 1 D8; predose (Hr 0), 0.5, 1, 2, 4, 6 Hr postdose (2, 4 Hr postdose for Cohorts II, III) on Cy1 D15; Expansion: predose (Hr 0), 1-4 Hr postdose on Cy1 D15; predose (Hr 0) on Cy2 D15 (Cy=28 days)

ID	Title	Description
OG000	Cohort I: Safety Run-In	Participants received cobimetinib plus paclitaxel until 12 participants completed one cycle of study treatment (28 days).
OG001	Cohort I: Cobimetinib, Paclitaxel	Participants received a combination of cobimetinib plus paclitaxel in 28-day cycles until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.
OG002	Cohort II:Cobimetinib,Paclitaxel,Atezolizumab	Participants received cobimetinib plus paclitaxel plus atezolizumab in 28-day cycles until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.

Secondary

Cohort I: Area Under the Concentration-Time Curve From Time Zero to Dosing Interval (AUC0-tau; Total Exposure) of Cobimetinib

The PK population included all participants with evaluable PK data who received at least one dose of study drug. Data were only collected from participants in the Cohort I: Safety Run-In stage for this outcome measure.

Posted

Geometric Mean

Geometric Coefficient of Variation

Nanograms/milliliter/hour (hr*ng/mL)

Safety Run-In: Predose (Hr 0) on Cy 1 D8; predose (Hr 0), 0.5, 1, 2, 4, 6 Hr postdose on Cy1 D15; Expansion: predose (Hr 0), 1-4 Hr postdose on Cy1 D15 (Cy=28 days)

ID	Title	Description
OG000	Cohort I: Safety Run-In	Participants received cobimetinib plus paclitaxel until 12 participants completed one cycle of study treatment (28 days).

Units	Counts
Participants	OG000

Secondary

Cohort I, II: Cmax of Paclitaxel

The PK population included all participants with evaluable PK data who received at least one dose of study drug. Data were only collected from Cohort I: Safety Run-In and Cohort II participants for this outcome measure.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Safety Run-In: Predose (Hr 0) on Cy1 D8; predose (Hr 0), 0.5, 1, 2, 4, and 6 Hr postdose (2, 4 Hr postdose for Cohort II) (infusion duration: 1 Hr) on Cy1 D15 (Cy=28 days)

ID	Title	Description
OG000	Cohort I: Safety Run-In	Participants received cobimetinib plus paclitaxel until 12 participants completed one cycle of study treatment (28 days).
OG001	Cohort II:Cobimetinib,Paclitaxel,Atezolizumab	Participants received cobimetinib plus paclitaxel plus atezolizumab in 28-day cycles until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.

Units	Counts
Participants	OG000

Secondary

Cohort I, II: Cmin of Paclitaxel

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Safety Run-In: Predose (Hr 0) on Cy1 D8; predose (Hr 0), 0.5, 1, 2, 4, and 6 Hr postdose (2, 4 Hr postdose for Cohort II) (infusion duration: 1 Hr) on Cy1 D15 (Cy=28 days)

ID	Title	Description
OG000	Cohort I: Safety Run-In	Participants received cobimetinib plus paclitaxel until 12 participants completed one cycle of study treatment (28 days).
OG001	Cohort II:Cobimetinib,Paclitaxel,Atezolizumab	Participants received cobimetinib plus paclitaxel plus atezolizumab in 28-day cycles until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.

Units	Counts
Participants	OG000

Secondary

Cohort I: AUC0-tau of Paclitaxel

Posted

Geometric Mean

Geometric Coefficient of Variation

hr*ng/mL

Safety Run-In: Predose (Hr 0) on Cy1 D8; predose (Hr 0), 0.5, 1, 2, 4, and 6 Hr postdose (infusion duration: 1 Hr) on Cy1 D15 (Cy=28 days)

ID	Title	Description
OG000	Cohort I: Safety Run-In	Participants received cobimetinib plus paclitaxel until 12 participants completed one cycle of study treatment (28 days).

Units	Counts
Participants	OG000

Secondary

Cohort III: Cmax of Nab-Paclitaxel

The PK population included all participants with evaluable PK data who received at least one dose of study drug

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Safety Run-In: Predose (Hr 0) on Cy1 D8; predose (Hr 0), 2, 4 Hr postdose (infusion duration: 30 minutes) on Cy1 D15 (Cy=28 days)

ID	Title	Description
OG000	Cohort III: Cobimetinib, Nab-Paclitaxel, Atezolizumab	Participants received cobimetinib plus nab-paclitaxel plus atezolizumab until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.

Units	Counts
Participants	OG000

Secondary

Cohort III: Cmin of Nab-Paclitaxel

The PK population included all participants with evaluable PK data who received at least one dose of study drug

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Safety Run-In: Predose (Hr 0) on Cy1 D8; predose (Hr 0), 2, 4 Hr postdose (infusion duration: 30 minutes) on Cy1 D15 (Cy=28 days)

ID	Title	Description
OG000	Cohort III: Cobimetinib, Nab-Paclitaxel, Atezolizumab	Participants received cobimetinib plus nab-paclitaxel plus atezolizumab until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.

Units	Counts
Participants	OG000

Secondary

Cohort III: AUC0-tau of Nab-Paclitaxel

The PK population included all participants with evaluable PK data who received at least one dose of study drug. Due to the sparse nature of PK sampling, the estimation of this PK parameter requires the use of population PK analysis. This would have enabled the exposure-response analysis with this OM. Given the outcome of the study, the Sponsors did not proceed with popPK analysis, which was planned, only if data warranted. AUC0-tau was not estimated and analyzed using the sparse PK samples.

Posted

Safety Run-In: Predose (Hr 0) on Cy1 D8; predose (Hr 0), 2, 4 Hr postdose (infusion duration: 30 minutes) on Cy1 D15 (Cy=28 days)

ID	Title	Description
OG000	Cohort III: Cobimetinib, Nab-Paclitaxel, Atezolizumab	Participants received cobimetinib plus nab-paclitaxel plus atezolizumab until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.

Units	Counts
Participants	OG000

Secondary

Cohort II, III: Cmax (in Serum) of Atezolizumab

The PK population included all participants with evaluable PK data who received at least one dose of study drug

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Safety Run-In, Expansion:Predose (Hr0), 0.5Hr postdose (infusion duration:1Hr) on D1 of Cy1, 3; predose (Hr0) on D1 of Cy2, 4, 8, every 8 Cy up to end of treatment (EOT); 120 days after EOT (approximately 5.25 years) (Cy=28 days)

ID	Title	Description
OG000	Cohort II:Cobimetinib,Paclitaxel,Atezolizumab	Participants received cobimetinib plus paclitaxel plus atezolizumab in 28-day cycles until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.
OG001	Cohort III: Cobimetinib, Nab-Paclitaxel, Atezolizumab	Participants received cobimetinib plus nab-paclitaxel plus atezolizumab until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.

Units	Counts
Participants

Secondary

Cohort II, III: Cmin (in Serum) of Atezolizumab

The PK population included all participants with evaluable PK data who received at least one dose of study drug

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Safety Run-In, Expansion: Predose (Hr 0), 0.5 Hr postdose (infusion duration: 1 Hr) on D1 of Cy1, 3; predose (Hr 0) on D1 of Cy2, 4, 8, every 8 Cy up to EOT; 120 days after EOT (approximately 5.5 years) (Cy=28 days)

ID	Title	Description
OG000	Cohort II:Cobimetinib,Paclitaxel,Atezolizumab	Participants received cobimetinib plus paclitaxel plus atezolizumab in 28-day cycles until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.
OG001	Cohort III: Cobimetinib, Nab-Paclitaxel, Atezolizumab	Participants received cobimetinib plus nab-paclitaxel plus atezolizumab until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.

Units	Counts
Participants

Secondary

Cohort II, III: AUC0-tau (in Serum) of Atezolizumab

Posted

Safety Run-In, Expansion: Predose (Hr 0), 0.5 Hr postdose (infusion duration: 1 Hr) on D1 of Cy1, 3; predose (Hr 0) on D1 of Cy2, 4, 8, every 8 Cy up to EOT (approximately 5.5 years); 120 days after EOT (approximately 5.5 years) (Cy=28 days)

ID	Title	Description
OG000	Cohort II:Cobimetinib,Paclitaxel,Atezolizumab	Participants received cobimetinib plus paclitaxel plus atezolizumab in 28-day cycles until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.
OG001	Cohort III: Cobimetinib, Nab-Paclitaxel, Atezolizumab	Participants received cobimetinib plus nab-paclitaxel plus atezolizumab until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
FEBRILE NEUTROPENIA	Blood and lymphatic system disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected43 at risk EG0021 events1 affected47 at risk EG0031 events1 affected32 at risk EG0041 events1 affected30 at risk
NEUTROPENIA	Blood and lymphatic system disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0021 events1 affected47 at risk EG003
CARDIAC ARREST	Cardiac disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0021 events1 affected47 at risk EG003
CARDIAC FAILURE	Cardiac disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected43 at risk EG0020 events0 affected47 at risk EG003
MITRAL VALVE INCOMPETENCE	Cardiac disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
PAPILLOEDEMA	Eye disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
ABDOMINAL PAIN	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
DIARRHOEA	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0021 events1 affected47 at risk EG003
GASTRIC PERFORATION	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
INTESTINAL OBSTRUCTION	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
NAUSEA	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
VOMITING	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
ASTHENIA	General disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0011 events1 affected43 at risk EG0020 events0 affected47 at risk EG003
FATIGUE	General disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected43 at risk EG0020 events0 affected47 at risk EG003
MUCOSAL INFLAMMATION	General disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
PYREXIA	General disorders	MedDRA v24.0	Systematic Assessment	EG0002 events2 affected16 at risk EG0010 events0 affected43 at risk EG0026 events6 affected47 at risk EG003
CELLULITIS	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0026 events4 affected47 at risk EG003
ERYSIPELAS	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0021 events1 affected47 at risk EG003
HERPES ZOSTER	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0021 events1 affected47 at risk EG003
KIDNEY INFECTION	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
MASTITIS	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
PERIORBITAL CELLULITIS	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
PNEUMOCYSTIS JIROVECII PNEUMONIA	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
PNEUMONIA	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0022 events2 affected47 at risk EG003
PYELONEPHRITIS ACUTE	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0021 events1 affected47 at risk EG003
SEPSIS	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0021 events1 affected47 at risk EG003
STREPTOCOCCAL SEPSIS	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0021 events1 affected47 at risk EG003
UPPER RESPIRATORY TRACT INFECTION	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
URINARY TRACT INFECTION	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0012 events1 affected43 at risk EG0025 events3 affected47 at risk EG003
BLOOD CREATININE INCREASED	Investigations	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
DECREASED APPETITE	Metabolism and nutrition disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
HYPOKALAEMIA	Metabolism and nutrition disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected43 at risk EG0020 events0 affected47 at risk EG003
BACK PAIN	Musculoskeletal and connective tissue disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected43 at risk EG0020 events0 affected47 at risk EG003
TUMOUR HAEMORRHAGE	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0021 events1 affected47 at risk EG003
BRAIN OEDEMA	Nervous system disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
ENCEPHALOPATHY	Nervous system disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
OPTIC NEURITIS	Nervous system disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
PARTIAL SEIZURES	Nervous system disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
PRESYNCOPE	Nervous system disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
SYNCOPE	Nervous system disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0021 events1 affected47 at risk EG003
DYSPNOEA	Respiratory, thoracic and mediastinal disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected43 at risk EG0023 events2 affected47 at risk EG003
EPISTAXIS	Respiratory, thoracic and mediastinal disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
LUNG INFILTRATION	Respiratory, thoracic and mediastinal disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
PLEURITIC PAIN	Respiratory, thoracic and mediastinal disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0021 events1 affected47 at risk EG003
PNEUMONITIS	Respiratory, thoracic and mediastinal disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0021 events1 affected47 at risk EG003
PULMONARY EMBOLISM	Respiratory, thoracic and mediastinal disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
RESPIRATORY FAILURE	Respiratory, thoracic and mediastinal disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0021 events1 affected47 at risk EG003
RASH	Skin and subcutaneous tissue disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
RASH ERYTHEMATOUS	Skin and subcutaneous tissue disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
EMBOLISM	Vascular disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
EMBOLISM VENOUS	Vascular disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected43 at risk EG0020 events0 affected47 at risk EG003
ORTHOSTATIC HYPOTENSION	Vascular disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
ANAEMIA	Blood and lymphatic system disorders	MedDRA v24.0	Systematic Assessment	EG0003 events3 affected16 at risk EG0019 events6 affected43 at risk EG00216 events12 affected47 at risk EG00319 events14 affected32 at risk EG00424 events10 affected30 at risk
EOSINOPHILIA	Blood and lymphatic system disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
LEUKOPENIA	Blood and lymphatic system disorders	MedDRA v24.0	Systematic Assessment	EG0006 events1 affected16 at risk EG0012 events1 affected43 at risk EG0021 events1 affected47 at risk EG003
NEUTROPENIA	Blood and lymphatic system disorders	MedDRA v24.0	Systematic Assessment	EG00016 events2 affected16 at risk EG00143 events13 affected43 at risk EG00221 events8 affected47 at risk EG003
PALPITATIONS	Cardiac disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0011 events1 affected43 at risk EG0022 events2 affected47 at risk EG003
TACHYCARDIA	Cardiac disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0021 events1 affected47 at risk EG003
TINNITUS	Ear and labyrinth disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
HYPOTHYROIDISM	Endocrine disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
CATARACT	Eye disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
CATARACT CORTICAL	Eye disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
CHORIORETINOPATHY	Eye disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0021 events1 affected47 at risk EG003
CONJUNCTIVAL HAEMORRHAGE	Eye disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
DRY EYE	Eye disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0013 events3 affected43 at risk EG0024 events4 affected47 at risk EG003
EPISCLERITIS	Eye disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
EYE PAIN	Eye disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0022 events2 affected47 at risk EG003
EYELID OEDEMA	Eye disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0011 events1 affected43 at risk EG0022 events2 affected47 at risk EG003
MACULAR FIBROSIS	Eye disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
MACULAR OEDEMA	Eye disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0021 events1 affected47 at risk EG003
RETINAL DETACHMENT	Eye disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
RETINAL DRUSEN	Eye disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
VISION BLURRED	Eye disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected43 at risk EG00211 events10 affected47 at risk EG003
VITREOUS FLOATERS	Eye disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
ABDOMINAL DISTENSION	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0021 events1 affected47 at risk EG003
ABDOMINAL PAIN	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG0003 events3 affected16 at risk EG0013 events3 affected43 at risk EG0026 events5 affected47 at risk EG003
ABDOMINAL PAIN UPPER	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0015 events4 affected43 at risk EG0026 events6 affected47 at risk EG003
APHTHOUS ULCER	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
CONSTIPATION	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG0004 events4 affected16 at risk EG00111 events9 affected43 at risk EG00211 events8 affected47 at risk EG003
DIARRHOEA	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG00029 events10 affected16 at risk EG00119 events13 affected43 at risk EG00266 events36 affected47 at risk EG003
DRY MOUTH	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG0002 events2 affected16 at risk EG0011 events1 affected43 at risk EG0026 events6 affected47 at risk EG003
DYSPEPSIA	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0013 events3 affected43 at risk EG0029 events6 affected47 at risk EG003
DYSPHAGIA	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0012 events2 affected43 at risk EG0022 events2 affected47 at risk EG003
GASTROOESOPHAGEAL REFLUX DISEASE	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG0006 events2 affected16 at risk EG0011 events1 affected43 at risk EG0022 events2 affected47 at risk EG003
HAEMORRHOIDS	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0012 events2 affected43 at risk EG0022 events1 affected47 at risk EG003
MOUTH ULCERATION	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0023 events2 affected47 at risk EG003
NAUSEA	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG0007 events7 affected16 at risk EG00125 events18 affected43 at risk EG00224 events20 affected47 at risk EG003
STOMATITIS	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG0008 events5 affected16 at risk EG0015 events5 affected43 at risk EG00218 events13 affected47 at risk EG003
VOMITING	Gastrointestinal disorders	MedDRA v24.0	Systematic Assessment	EG0006 events5 affected16 at risk EG0018 events7 affected43 at risk EG00213 events8 affected47 at risk EG003
ASTHENIA	General disorders	MedDRA v24.0	Systematic Assessment	EG0003 events3 affected16 at risk EG00118 events11 affected43 at risk EG00215 events13 affected47 at risk EG003
CHEST PAIN	General disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0019 events7 affected43 at risk EG0025 events5 affected47 at risk EG003
CHILLS	General disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0023 events3 affected47 at risk EG003
FATIGUE	General disorders	MedDRA v24.0	Systematic Assessment	EG0003 events3 affected16 at risk EG00119 events15 affected43 at risk EG00215 events13 affected47 at risk EG003
GAIT DISTURBANCE	General disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
GENERALISED OEDEMA	General disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0021 events1 affected47 at risk EG003
INFLUENZA LIKE ILLNESS	General disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0023 events3 affected47 at risk EG003
MUCOSAL INFLAMMATION	General disorders	MedDRA v24.0	Systematic Assessment	EG0003 events1 affected16 at risk EG0013 events2 affected43 at risk EG0029 events4 affected47 at risk EG003
OEDEMA	General disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0012 events2 affected43 at risk EG0027 events5 affected47 at risk EG003
OEDEMA PERIPHERAL	General disorders	MedDRA v24.0	Systematic Assessment	EG0004 events4 affected16 at risk EG0019 events9 affected43 at risk EG00212 events9 affected47 at risk EG003
PAIN	General disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0013 events3 affected43 at risk EG0023 events3 affected47 at risk EG003
PERIPHERAL SWELLING	General disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0021 events1 affected47 at risk EG003
PYREXIA	General disorders	MedDRA v24.0	Systematic Assessment	EG0007 events4 affected16 at risk EG00113 events8 affected43 at risk EG00215 events9 affected47 at risk EG003
CELLULITIS	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected43 at risk EG0020 events0 affected47 at risk EG003
CYSTITIS	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected43 at risk EG0024 events3 affected47 at risk EG003
FURUNCLE	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
IMPETIGO	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
INFLUENZA	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0011 events1 affected43 at risk EG0020 events0 affected47 at risk EG003
LARYNGITIS	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0022 events2 affected47 at risk EG003
LOCALISED INFECTION	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
LYMPHANGITIS	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
NAIL INFECTION	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0022 events2 affected47 at risk EG003
NASOPHARYNGITIS	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0011 events1 affected43 at risk EG0024 events2 affected47 at risk EG003
ORAL HERPES	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected43 at risk EG0020 events0 affected47 at risk EG003
PARONYCHIA	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0014 events2 affected43 at risk EG0025 events4 affected47 at risk EG003
PHARYNGITIS	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0023 events3 affected47 at risk EG003
PNEUMONIA	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected43 at risk EG0023 events3 affected47 at risk EG003
RASH PUSTULAR	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected43 at risk EG0021 events1 affected47 at risk EG003
SINUSITIS	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
UPPER RESPIRATORY TRACT INFECTION	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0004 events2 affected16 at risk EG0016 events4 affected43 at risk EG0023 events3 affected47 at risk EG003
URINARY TRACT INFECTION	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0003 events2 affected16 at risk EG0014 events1 affected43 at risk EG0026 events4 affected47 at risk EG003
VAGINAL INFECTION	Infections and infestations	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
CHEST INJURY	Injury, poisoning and procedural complications	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
INFUSION RELATED REACTION	Injury, poisoning and procedural complications	MedDRA v24.0	Systematic Assessment	EG0003 events2 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
ALANINE AMINOTRANSFERASE INCREASED	Investigations	MedDRA v24.0	Systematic Assessment	EG0004 events2 affected16 at risk EG0015 events3 affected43 at risk EG0024 events3 affected47 at risk EG003
ASPARTATE AMINOTRANSFERASE INCREASED	Investigations	MedDRA v24.0	Systematic Assessment	EG0005 events3 affected16 at risk EG0012 events2 affected43 at risk EG0025 events3 affected47 at risk EG003
BLOOD ALKALINE PHOSPHATASE INCREASED	Investigations	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0012 events1 affected43 at risk EG0023 events3 affected47 at risk EG003
BLOOD CREATINE PHOSPHOKINASE INCREASED	Investigations	MedDRA v24.0	Systematic Assessment	EG0006 events6 affected16 at risk EG0010 events0 affected43 at risk EG00210 events10 affected47 at risk EG003
BLOOD POTASSIUM DECREASED	Investigations	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
BLOOD PRESSURE INCREASED	Investigations	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
BLOOD THYROID STIMULATING HORMONE INCREASED	Investigations	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
C-REACTIVE PROTEIN INCREASED	Investigations	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
CARBOHYDRATE ANTIGEN 15-3 INCREASED	Investigations	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
EJECTION FRACTION DECREASED	Investigations	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0023 events3 affected47 at risk EG003
FIBRIN D DIMER INCREASED	Investigations	MedDRA v24.0	Systematic Assessment	EG0002 events2 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
GAMMA-GLUTAMYLTRANSFERASE INCREASED	Investigations	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0015 events2 affected43 at risk EG0021 events1 affected47 at risk EG003
HAEMOGLOBIN DECREASED	Investigations	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0012 events2 affected43 at risk EG0021 events1 affected47 at risk EG003
MYOGLOBIN BLOOD INCREASED	Investigations	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
NEUTROPHIL COUNT DECREASED	Investigations	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected43 at risk EG0022 events2 affected47 at risk EG003
NEUTROPHIL COUNT INCREASED	Investigations	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
PLATELET COUNT DECREASED	Investigations	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0012 events1 affected43 at risk EG0020 events0 affected47 at risk EG003
SERUM FERRITIN INCREASED	Investigations	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
TRANSFERRIN SATURATION DECREASED	Investigations	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0021 events1 affected47 at risk EG003
WEIGHT DECREASED	Investigations	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0014 events3 affected43 at risk EG0020 events0 affected47 at risk EG003
WHITE BLOOD CELL COUNT DECREASED	Investigations	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
WHITE BLOOD CELL COUNT INCREASED	Investigations	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
DECREASED APPETITE	Metabolism and nutrition disorders	MedDRA v24.0	Systematic Assessment	EG0003 events3 affected16 at risk EG00114 events10 affected43 at risk EG00211 events9 affected47 at risk EG003
DEHYDRATION	Metabolism and nutrition disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
DIABETES MELLITUS	Metabolism and nutrition disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
HYPOKALAEMIA	Metabolism and nutrition disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected43 at risk EG0028 events5 affected47 at risk EG003
HYPOMAGNESAEMIA	Metabolism and nutrition disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0023 events2 affected47 at risk EG003
HYPOPHOSPHATAEMIA	Metabolism and nutrition disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected43 at risk EG0023 events2 affected47 at risk EG003
ARTHRALGIA	Musculoskeletal and connective tissue disorders	MedDRA v24.0	Systematic Assessment	EG0002 events2 affected16 at risk EG0019 events7 affected43 at risk EG0024 events2 affected47 at risk EG003
BACK PAIN	Musculoskeletal and connective tissue disorders	MedDRA v24.0	Systematic Assessment	EG0002 events2 affected16 at risk EG0012 events2 affected43 at risk EG0026 events6 affected47 at risk EG003
BONE PAIN	Musculoskeletal and connective tissue disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0015 events4 affected43 at risk EG0021 events1 affected47 at risk EG003
JOINT SWELLING	Musculoskeletal and connective tissue disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
MUSCLE SPASMS	Musculoskeletal and connective tissue disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0012 events2 affected43 at risk EG0021 events1 affected47 at risk EG003
MUSCULAR WEAKNESS	Musculoskeletal and connective tissue disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
MUSCULOSKELETAL CHEST PAIN	Musculoskeletal and connective tissue disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0012 events2 affected43 at risk EG0022 events2 affected47 at risk EG003
MYALGIA	Musculoskeletal and connective tissue disorders	MedDRA v24.0	Systematic Assessment	EG0002 events2 affected16 at risk EG0018 events6 affected43 at risk EG0028 events6 affected47 at risk EG003
NECK PAIN	Musculoskeletal and connective tissue disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected43 at risk EG0022 events2 affected47 at risk EG003
PAIN IN EXTREMITY	Musculoskeletal and connective tissue disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0015 events5 affected43 at risk EG0022 events2 affected47 at risk EG003
DIZZINESS	Nervous system disorders	MedDRA v24.0	Systematic Assessment	EG0003 events3 affected16 at risk EG0019 events8 affected43 at risk EG0029 events7 affected47 at risk EG003
DYSGEUSIA	Nervous system disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0014 events4 affected43 at risk EG0027 events7 affected47 at risk EG003
DYSMETRIA	Nervous system disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
DYSTONIC TREMOR	Nervous system disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
HEADACHE	Nervous system disorders	MedDRA v24.0	Systematic Assessment	EG0003 events3 affected16 at risk EG00114 events9 affected43 at risk EG00214 events7 affected47 at risk EG003
HYPOAESTHESIA	Nervous system disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0012 events2 affected43 at risk EG0023 events3 affected47 at risk EG003
HYPOGEUSIA	Nervous system disorders	MedDRA v24.0	Systematic Assessment	EG0002 events2 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
NEUROPATHY PERIPHERAL	Nervous system disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG00110 events7 affected43 at risk EG0024 events4 affected47 at risk EG003
NEUROTOXICITY	Nervous system disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0014 events3 affected43 at risk EG0020 events0 affected47 at risk EG003
PARAESTHESIA	Nervous system disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0019 events5 affected43 at risk EG0025 events4 affected47 at risk EG003
PERIPHERAL SENSORY NEUROPATHY	Nervous system disorders	MedDRA v24.0	Systematic Assessment	EG0002 events2 affected16 at risk EG00112 events9 affected43 at risk EG00212 events8 affected47 at risk EG003
ANXIETY	Psychiatric disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected43 at risk EG0023 events2 affected47 at risk EG003
INSOMNIA	Psychiatric disorders	MedDRA v24.0	Systematic Assessment	EG0002 events2 affected16 at risk EG0018 events7 affected43 at risk EG0023 events3 affected47 at risk EG003
ACUTE KIDNEY INJURY	Renal and urinary disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
DYSURIA	Renal and urinary disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0011 events1 affected43 at risk EG0025 events4 affected47 at risk EG003
HAEMATURIA	Renal and urinary disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0023 events3 affected47 at risk EG003
BREAST PAIN	Reproductive system and breast disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0015 events3 affected43 at risk EG0021 events1 affected47 at risk EG003
CYSTOCELE	Reproductive system and breast disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
COUGH	Respiratory, thoracic and mediastinal disorders	MedDRA v24.0	Systematic Assessment	EG0002 events2 affected16 at risk EG00114 events12 affected43 at risk EG0028 events7 affected47 at risk EG003
DYSPHONIA	Respiratory, thoracic and mediastinal disorders	MedDRA v24.0	Systematic Assessment	EG0002 events2 affected16 at risk EG0013 events3 affected43 at risk EG0023 events2 affected47 at risk EG003
DYSPNOEA	Respiratory, thoracic and mediastinal disorders	MedDRA v24.0	Systematic Assessment	EG0005 events4 affected16 at risk EG0016 events3 affected43 at risk EG00212 events7 affected47 at risk EG003
EPISTAXIS	Respiratory, thoracic and mediastinal disorders	MedDRA v24.0	Systematic Assessment	EG0002 events2 affected16 at risk EG0015 events4 affected43 at risk EG0025 events4 affected47 at risk EG003
NASAL DRYNESS	Respiratory, thoracic and mediastinal disorders	MedDRA v24.0	Systematic Assessment	EG0002 events2 affected16 at risk EG0010 events0 affected43 at risk EG0022 events2 affected47 at risk EG003
OROPHARYNGEAL PAIN	Respiratory, thoracic and mediastinal disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected43 at risk EG0024 events4 affected47 at risk EG003
PLEURAL EFFUSION	Respiratory, thoracic and mediastinal disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected43 at risk EG0023 events3 affected47 at risk EG003
PNEUMONITIS	Respiratory, thoracic and mediastinal disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected43 at risk EG0020 events0 affected47 at risk EG003
PRODUCTIVE COUGH	Respiratory, thoracic and mediastinal disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0013 events3 affected43 at risk EG0021 events1 affected47 at risk EG003
PULMONARY EMBOLISM	Respiratory, thoracic and mediastinal disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
ALOPECIA	Skin and subcutaneous tissue disorders	MedDRA v24.0	Systematic Assessment	EG0005 events5 affected16 at risk EG00120 events19 affected43 at risk EG00222 events21 affected47 at risk EG003
DERMATITIS ACNEIFORM	Skin and subcutaneous tissue disorders	MedDRA v24.0	Systematic Assessment	EG0003 events3 affected16 at risk EG0014 events3 affected43 at risk EG00212 events9 affected47 at risk EG003
DRY SKIN	Skin and subcutaneous tissue disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0027 events6 affected47 at risk EG003
ERYTHEMA	Skin and subcutaneous tissue disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0011 events1 affected43 at risk EG0023 events2 affected47 at risk EG003
ERYTHEMA NODOSUM	Skin and subcutaneous tissue disorders	MedDRA v24.0	Systematic Assessment	EG0002 events1 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
INGROWING NAIL	Skin and subcutaneous tissue disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0021 events1 affected47 at risk EG003
NAIL DISCOLOURATION	Skin and subcutaneous tissue disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0011 events1 affected43 at risk EG0023 events3 affected47 at risk EG003
NAIL RIDGING	Skin and subcutaneous tissue disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
ONYCHOMADESIS	Skin and subcutaneous tissue disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0021 events1 affected47 at risk EG003
PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME	Skin and subcutaneous tissue disorders	MedDRA v24.0	Systematic Assessment	EG0004 events1 affected16 at risk EG0011 events1 affected43 at risk EG0020 events0 affected47 at risk EG003
PRURITUS	Skin and subcutaneous tissue disorders	MedDRA v24.0	Systematic Assessment	EG0002 events2 affected16 at risk EG0012 events2 affected43 at risk EG00217 events12 affected47 at risk EG003
RASH	Skin and subcutaneous tissue disorders	MedDRA v24.0	Systematic Assessment	EG00018 events8 affected16 at risk EG0016 events5 affected43 at risk EG00234 events22 affected47 at risk EG003
RASH MACULO-PAPULAR	Skin and subcutaneous tissue disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0011 events1 affected43 at risk EG0021 events1 affected47 at risk EG003
RASH PAPULAR	Skin and subcutaneous tissue disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
SKIN FISSURES	Skin and subcutaneous tissue disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0010 events0 affected43 at risk EG0024 events3 affected47 at risk EG003
SKIN LESION	Skin and subcutaneous tissue disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0010 events0 affected43 at risk EG0020 events0 affected47 at risk EG003
FLUSHING	Vascular disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0012 events2 affected43 at risk EG0021 events1 affected47 at risk EG003
HOT FLUSH	Vascular disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0012 events2 affected43 at risk EG0021 events1 affected47 at risk EG003
HYPERTENSION	Vascular disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0015 events3 affected43 at risk EG0027 events4 affected47 at risk EG003
HYPOTENSION	Vascular disorders	MedDRA v24.0	Systematic Assessment	EG0001 events1 affected16 at risk EG0011 events1 affected43 at risk EG0020 events0 affected47 at risk EG003
LYMPHOEDEMA	Vascular disorders	MedDRA v24.0	Systematic Assessment	EG0000 events0 affected16 at risk EG0013 events1 affected43 at risk EG0024 events4 affected47 at risk EG003

ID	Term
D009371	Neoplasms by Site
D009369	Neoplasms
D001941	Breast Diseases
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases

ID	Term
D043823	Taxoids
D043822	Cyclodecanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009930	Organic Chemicals
D004224	Diterpenes
D013729	Terpenes

ID	Title	Description
BG000	Cohort I: Safety Run-In	Participants received cobimetinib plus paclitaxel until 12 participants completed one cycle of study treatment (28 days).
BG001	Cohort I: Placebo, Paclitaxel	Participants received a combination of cobimetinib placebo plus paclitaxel in 28-day cycles until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.
BG002	Cohort I: Cobimetinib, Paclitaxel	Participants received a combination of cobimetinib plus paclitaxel in 28-day cycles until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.
BG003	Cohort II:Cobimetinib,Paclitaxel,Atezolizumab	Participants received cobimetinib plus paclitaxel plus atezolizumab in 28-day cycles until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.
BG004	Cohort III: Cobimetinib, Nab-Paclitaxel, Atezolizumab	Participants received cobimetinib plus nab-paclitaxel plus atezolizumab until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.
BG005	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Cohort I: Safety Run-In	Participants received cobimetinib plus paclitaxel until 12 participants completed one cycle of study treatment (28 days).	7	16	6	16	15	16
EG001	Cohort I: Placebo, Paclitaxel	Participants received a combination of cobimetinib placebo plus paclitaxel in 28-day cycles until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.	29	43	8	43	43	43
EG002	Cohort I: Cobimetinib, Paclitaxel	Participants received a combination of cobimetinib plus paclitaxel in 28-day cycles until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.	32	47	17	47	46	47
EG003	Cohort II:Cobimetinib,Paclitaxel,Atezolizumab	Participants received cobimetinib plus paclitaxel plus atezolizumab in 28-day cycles until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.	23	32	16	32	32	32
EG004	Cohort III: Cobimetinib, Nab-Paclitaxel, Atezolizumab	Participants received cobimetinib plus nab-paclitaxel plus atezolizumab until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.	14	31	15	30	29	30

ID	Term
C574276	cobimetinib
D017239	Paclitaxel
C000594389	atezolizumab
C520255	130-nm albumin-bound paclitaxel