Non-Small Cell Lung Cancer, Metastatic Colorectal Cancer, Metastatic Non Small Cell Lung Cancer, Metastatic Cancers, Melanoma
Conditions
Brief summary
This is a two-stage dose-escalation study to assess the safety, tolerability and effects of oral dosing of cobimetinib and GDC-0994 administered in combination in patients with histologically confirmed, locally advanced, or metastatic solid tumors for which standard therapies either do not exist or have proven ineffective or intolerable.
Interventions
DRUGCobimetinib
Cobimetinib given concurrently or intermittently with GDC-0994 for 21 consecutive days followed by 7 days off.
DRUGGDC-0994
GDC-0994 given for 21 consecutive days followed by 7 days off, along with concurrent or intermittent dosing of cobimetinib.
Sponsors
Genentech, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Weight | Baseline, up to 15 months | — |
| Percentage of Participants With at Least One Adverse Event | Up to 15 months | An adverse event is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. |
| Percentage of Participants With at Least One Adverse Event of Special Interest | Up to 15 months | 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. |
| Percentage of Participants With at Least One Serious Adverse Event (SAE) | Up to 15 months | 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. |
| Percentage of Participants With Laboratory Abnormalities | Up to 15 months | 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 |
| Mean Change From Baseline in Diastolic Blood Pressure | Baseline, up to 15 months | — |
| Mean Change From Baseline in Lean Body Mass | Baseline, Day 15 | — |
| Mean Change From Baseline in Pulse Rate | Baseline, up to 15 months | — |
| Mean Change From Baseline in Respiratory Rate | Baseline, up to 15 months | — |
| Mean Change From Baseline in Systolic Blood Pressure | Baseline, up to 15 months | — |
| Mean Change From Baseline in Temperature | Baseline, up to 15 months | — |
| Number of Participants With Dose-Limiting Toxicities (DLTs) | 28 days (Cycle 1) | DLTs include symptoms considered by the investigator to be possibly related to study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Serum Concentration (Cmax) for GDC-0994 | Up to Day 22 | — |
| Maximum Serum Concentration (Cmax) for Cobimetinib | Up to Day 22 | — |
| Median Time to Maximum Serum Concentration (Tmax) for Cobimetinib | Up to Day 22 | — |
| Total Exposure (AUC From Time 0 to 24 Hour After Dose) for GDC-0994 | 0 to 24 hours post-dose (Up to Day 22) | Data are reported for evaluable participants. |
| Total Exposure (AUC From Time 0 to 24 Hour After Dose) for Cobimetinib | 0 to 24 hours post-dose (Up to Day 22) | — |
| Mean Accumulation Ratio | 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 | — |
| Mean Terminal Half-life (t1/2) | Up to day 22 of study | — |
| Change From Baseline in Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) | Baseline, Day 15 | — |
| Change From Baseline in Tumor Tissue Biomarkers | Up to 15 months | — |
| Median Time to Maximum Serum Concentration (Tmax) for GDC-0994 | Up to Day 22 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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 |
| 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. | 5 |
| 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. | 3 |
| 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. | 5 |
| 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. | 4 |
| 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. | 6 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Physician Decision | 1 | 0 | 1 | 1 | 1 | 3 |
| Overall Study | Reason not specified | 0 | 0 | 0 | 1 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 4 | 2 | 2 | 2 | 2 |
Baseline characteristics
| Characteristic | Not Assigned | COB 20 mg + GDC 200 mg | COB 40 mg + GDC 200 mg | COB 80 mg + GDC 200 mg | COB 80 mg + GDC 400 mg | COB 100 mg + GDC 200 mg | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 48.0 Years STANDARD_DEVIATION 9999 | 53.0 Years STANDARD_DEVIATION 11.5 | 57.3 Years STANDARD_DEVIATION 11 | 51.6 Years STANDARD_DEVIATION 14.2 | 52.3 Years STANDARD_DEVIATION 5.6 | 59.7 Years STANDARD_DEVIATION 11.5 | 54.6 Years STANDARD_DEVIATION 10.7 |
| Sex: Female, Male Female | 0 Participants | 5 Participants | 3 Participants | 4 Participants | 2 Participants | 3 Participants | 17 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 3 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 1 | 5 / 5 | 3 / 3 | 5 / 5 | 4 / 4 | 6 / 6 |
| serious Total, serious adverse events | 1 / 1 | 2 / 5 | 2 / 3 | 3 / 5 | 2 / 4 | 4 / 6 |
Outcome results
Primary
Mean Change From Baseline in Diastolic Blood Pressure
Time frame: Baseline, up to 15 months
Population: All participants. Data are reported for evaluable participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| COB 20 mg + GDC 200 mg | Mean Change From Baseline in Diastolic Blood Pressure | -4.2 millimeters of mercury (mmHg) | Standard Deviation 7.6 |
| COB 40 mg + GDC 200 mg | Mean Change From Baseline in Diastolic Blood Pressure | -4.3 millimeters of mercury (mmHg) | Standard Deviation 11.8 |
| COB 80 mg + GDC 200 mg | Mean Change From Baseline in Diastolic Blood Pressure | -0.5 millimeters of mercury (mmHg) | Standard Deviation 7.8 |
| COB 80 mg + GDC 400 mg | Mean Change From Baseline in Diastolic Blood Pressure | 29.0 millimeters of mercury (mmHg) | — |
| COB 100 mg + GDC 200 mg | Mean Change From Baseline in Diastolic Blood Pressure | -13.2 millimeters of mercury (mmHg) | Standard Deviation 15.9 |
Primary
Mean Change From Baseline in Lean Body Mass
Time frame: Baseline, Day 15
Population: All participants. Data are reported for evaluable participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| COB 20 mg + GDC 200 mg | Mean Change From Baseline in Lean Body Mass | 0.25 kilograms (kg) | Standard Deviation 1.26 |
| COB 40 mg + GDC 200 mg | Mean Change From Baseline in Lean Body Mass | -2.00 kilograms (kg) | — |
| COB 80 mg + GDC 200 mg | Mean Change From Baseline in Lean Body Mass | -0.20 kilograms (kg) | Standard Deviation 1.3 |
| COB 80 mg + GDC 400 mg | Mean Change From Baseline in Lean Body Mass | -4.33 kilograms (kg) | Standard Deviation 5.77 |
| COB 100 mg + GDC 200 mg | Mean Change From Baseline in Lean Body Mass | 0.00 kilograms (kg) | Standard Deviation 1.41 |
Primary
Mean Change From Baseline in Pulse Rate
Time frame: Baseline, up to 15 months
Population: All participants. Data are reported for evaluable participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| COB 20 mg + GDC 200 mg | Mean Change From Baseline in Pulse Rate | 20.4 beats per minute | Standard Deviation 32.7 |
| COB 40 mg + GDC 200 mg | Mean Change From Baseline in Pulse Rate | 16.7 beats per minute | Standard Deviation 22.7 |
| COB 80 mg + GDC 200 mg | Mean Change From Baseline in Pulse Rate | 15.5 beats per minute | Standard Deviation 9.2 |
| COB 80 mg + GDC 400 mg | Mean Change From Baseline in Pulse Rate | 43.0 beats per minute | — |
| COB 100 mg + GDC 200 mg | Mean Change From Baseline in Pulse Rate | 12.2 beats per minute | Standard Deviation 21.6 |
Primary
Mean Change From Baseline in Respiratory Rate
Time frame: Baseline, up to 15 months
Population: All participants. Data are reported for evaluable participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| COB 20 mg + GDC 200 mg | Mean Change From Baseline in Respiratory Rate | 1.6 breaths per minute | Standard Deviation 3.6 |
| COB 40 mg + GDC 200 mg | Mean Change From Baseline in Respiratory Rate | 0.3 breaths per minute | Standard Deviation 0.6 |
| COB 80 mg + GDC 200 mg | Mean Change From Baseline in Respiratory Rate | 0.0 breaths per minute | Standard Deviation 0 |
| COB 80 mg + GDC 400 mg | Mean Change From Baseline in Respiratory Rate | 2.0 breaths per minute | — |
| COB 100 mg + GDC 200 mg | Mean Change From Baseline in Respiratory Rate | 1.6 breaths per minute | Standard Deviation 3.6 |
Primary
Mean Change From Baseline in Systolic Blood Pressure
Time frame: Baseline, up to 15 months
Population: All participants. Data are reported for evaluable participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| COB 20 mg + GDC 200 mg | Mean Change From Baseline in Systolic Blood Pressure | 2.2 mmHg | Standard Deviation 19.6 |
| COB 40 mg + GDC 200 mg | Mean Change From Baseline in Systolic Blood Pressure | -4.0 mmHg | Standard Deviation 30.6 |
| COB 80 mg + GDC 200 mg | Mean Change From Baseline in Systolic Blood Pressure | -1.5 mmHg | Standard Deviation 0.7 |
| COB 80 mg + GDC 400 mg | Mean Change From Baseline in Systolic Blood Pressure | 34.0 mmHg | — |
| COB 100 mg + GDC 200 mg | Mean Change From Baseline in Systolic Blood Pressure | -17.2 mmHg | Standard Deviation 20.9 |
Primary
Mean Change From Baseline in Temperature
Time frame: Baseline, up to 15 months
Population: All participants. Data are reported for evaluable participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| COB 20 mg + GDC 200 mg | Mean Change From Baseline in Temperature | -0.04 degrees Celsius | Standard Deviation 0.31 |
| COB 40 mg + GDC 200 mg | Mean Change From Baseline in Temperature | -0.20 degrees Celsius | Standard Deviation 0.87 |
| COB 80 mg + GDC 200 mg | Mean Change From Baseline in Temperature | -0.16 degrees Celsius | Standard Deviation 0.2 |
| COB 80 mg + GDC 400 mg | Mean Change From Baseline in Temperature | -0.20 degrees Celsius | — |
| COB 100 mg + GDC 200 mg | Mean Change From Baseline in Temperature | -0.16 degrees Celsius | Standard Deviation 0.34 |
Primary
Mean Change From Baseline in Weight
Time frame: Baseline, up to 15 months
Population: All participants. Data are reported for evaluable participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| COB 20 mg + GDC 200 mg | Mean Change From Baseline in Weight | -4.01 kg | Standard Deviation 7.71 |
| COB 40 mg + GDC 200 mg | Mean Change From Baseline in Weight | 0.33 kg | Standard Deviation 1.69 |
| COB 80 mg + GDC 200 mg | Mean Change From Baseline in Weight | 0.57 kg | Standard Deviation 3.34 |
| COB 80 mg + GDC 400 mg | Mean Change From Baseline in Weight | -2.70 kg | — |
| COB 100 mg + GDC 200 mg | Mean Change From Baseline in Weight | -0.80 kg | Standard Deviation 3.43 |
Primary
Number of Participants With Dose-Limiting Toxicities (DLTs)
DLTs include symptoms considered by the investigator to be possibly related to study drug.
Time frame: 28 days (Cycle 1)
Population: All participants.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Not Assigned | Number of Participants With Dose-Limiting Toxicities (DLTs) | Dermatitis Acneiform | 1 Participants |
| Not Assigned | Number of Participants With Dose-Limiting Toxicities (DLTs) | Rash | 1 Participants |
| Not Assigned | Number of Participants With Dose-Limiting Toxicities (DLTs) | Diarrhoea | 0 Participants |
| Not Assigned | Number of Participants With Dose-Limiting Toxicities (DLTs) | Myocardial infarction | 0 Participants |
| COB 20 mg + GDC 200 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) | Diarrhoea | 0 Participants |
| COB 20 mg + GDC 200 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) | Rash | 0 Participants |
| COB 20 mg + GDC 200 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) | Dermatitis Acneiform | 0 Participants |
| COB 20 mg + GDC 200 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) | Myocardial infarction | 0 Participants |
| COB 40 mg + GDC 200 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) | Myocardial infarction | 0 Participants |
| COB 40 mg + GDC 200 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) | Diarrhoea | 1 Participants |
| COB 40 mg + GDC 200 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) | Rash | 0 Participants |
| COB 40 mg + GDC 200 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) | Dermatitis Acneiform | 0 Participants |
| COB 80 mg + GDC 200 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) | Dermatitis Acneiform | 0 Participants |
| COB 80 mg + GDC 200 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) | Myocardial infarction | 1 Participants |
| COB 80 mg + GDC 200 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) | Rash | 0 Participants |
| COB 80 mg + GDC 200 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) | Diarrhoea | 0 Participants |
| COB 80 mg + GDC 400 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) | Diarrhoea | 0 Participants |
| COB 80 mg + GDC 400 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) | Myocardial infarction | 0 Participants |
| COB 80 mg + GDC 400 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) | Rash | 0 Participants |
| COB 80 mg + GDC 400 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) | Dermatitis Acneiform | 0 Participants |
| COB 100 mg + GDC 200 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) | Rash | 0 Participants |
| COB 100 mg + GDC 200 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) | Diarrhoea | 0 Participants |
| COB 100 mg + GDC 200 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) | Myocardial infarction | 0 Participants |
| COB 100 mg + GDC 200 mg | Number of Participants With Dose-Limiting Toxicities (DLTs) | Dermatitis Acneiform | 0 Participants |
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.
Time frame: Up to 15 months
Population: All participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Not Assigned | Percentage of Participants With at Least One Adverse Event | 100 percentage of participants |
| COB 20 mg + GDC 200 mg | Percentage of Participants With at Least One Adverse Event | 100 percentage of participants |
| COB 40 mg + GDC 200 mg | Percentage of Participants With at Least One Adverse Event | 100 percentage of participants |
| COB 80 mg + GDC 200 mg | Percentage of Participants With at Least One Adverse Event | 100 percentage of participants |
| COB 80 mg + GDC 400 mg | Percentage of Participants With at Least One Adverse Event | 100 percentage of participants |
| COB 100 mg + GDC 200 mg | Percentage of Participants With at Least One Adverse Event | 100 percentage of participants |
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.
Time frame: Up to 15 months
Population: All participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Not Assigned | Percentage of Participants With at Least One Adverse Event of Special Interest | 100.0 percentage of participants |
| COB 20 mg + GDC 200 mg | Percentage of Participants With at Least One Adverse Event of Special Interest | 100 percentage of participants |
| COB 40 mg + GDC 200 mg | Percentage of Participants With at Least One Adverse Event of Special Interest | 33.3 percentage of participants |
| COB 80 mg + GDC 200 mg | Percentage of Participants With at Least One Adverse Event of Special Interest | 60.0 percentage of participants |
| COB 80 mg + GDC 400 mg | Percentage of Participants With at Least One Adverse Event of Special Interest | 75.0 percentage of participants |
| COB 100 mg + GDC 200 mg | Percentage of Participants With at Least One Adverse Event of Special Interest | 50.0 percentage of participants |
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.
Time frame: Up to 15 months
Population: All participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Not Assigned | Percentage of Participants With at Least One Serious Adverse Event (SAE) | 100.0 percentage of participants |
| COB 20 mg + GDC 200 mg | Percentage of Participants With at Least One Serious Adverse Event (SAE) | 40.0 percentage of participants |
| COB 40 mg + GDC 200 mg | Percentage of Participants With at Least One Serious Adverse Event (SAE) | 66.7 percentage of participants |
| COB 80 mg + GDC 200 mg | Percentage of Participants With at Least One Serious Adverse Event (SAE) | 60.0 percentage of participants |
| COB 80 mg + GDC 400 mg | Percentage of Participants With at Least One Serious Adverse Event (SAE) | 50.0 percentage of participants |
| COB 100 mg + GDC 200 mg | Percentage of Participants With at Least One Serious Adverse Event (SAE) | 66.7 percentage of participants |
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
Time frame: Up to 15 months
Population: All participants. Data are reported for evaluable participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Not Assigned | Percentage of Participants With Laboratory Abnormalities | Hemoglobin | 100.0 percentage of participants |
| Not Assigned | Percentage of Participants With Laboratory Abnormalities | Sodium | 0.0 percentage of participants |
| Not Assigned | Percentage of Participants With Laboratory Abnormalities | Blood Glucose, Fasting | 0.0 percentage of participants |
| Not Assigned | Percentage of Participants With Laboratory Abnormalities | Albumin | 100.0 percentage of participants |
| Not Assigned | Percentage of Participants With Laboratory Abnormalities | Alkaline Phosphatase | 100.0 percentage of participants |
| Not Assigned | Percentage of Participants With Laboratory Abnormalities | Calcium | 100.0 percentage of participants |
| Not Assigned | Percentage of Participants With Laboratory Abnormalities | Phosphorus | 0.0 percentage of participants |
| Not Assigned | Percentage of Participants With Laboratory Abnormalities | Creatinine | 100.0 percentage of participants |
| Not Assigned | Percentage of Participants With Laboratory Abnormalities | Magnesium | 100.0 percentage of participants |
| Not Assigned | Percentage of Participants With Laboratory Abnormalities | Lymphocytes, Absolute | 100.0 percentage of participants |
| Not Assigned | Percentage of Participants With Laboratory Abnormalities | Bilirubin | 100.0 percentage of participants |
| Not Assigned | Percentage of Participants With Laboratory Abnormalities | Potassium | 0.0 percentage of participants |
| Not Assigned | Percentage of Participants With Laboratory Abnormalities | SGPT/ALT | 0.0 percentage of participants |
| Not Assigned | Percentage of Participants With Laboratory Abnormalities | Platelets | 0.0 percentage of participants |
| Not Assigned | Percentage of Participants With Laboratory Abnormalities | Gamma Glutamyl Transferase | 100.0 percentage of participants |
| Not Assigned | Percentage of Participants With Laboratory Abnormalities | White Blood Cell Count | 0.0 percentage of participants |
| Not Assigned | Percentage of Participants With Laboratory Abnormalities | Glucose | 0 percentage of participants |
| Not Assigned | Percentage of Participants With Laboratory Abnormalities | Uric Acid | 0.0 percentage of participants |
| Not Assigned | Percentage of Participants With Laboratory Abnormalities | SGOT/AST | 100.0 percentage of participants |
| COB 20 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Glucose | 20.0 percentage of participants |
| COB 20 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Lymphocytes, Absolute | 40.0 percentage of participants |
| COB 20 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Phosphorus | 20.0 percentage of participants |
| COB 20 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Magnesium | 40.0 percentage of participants |
| COB 20 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | SGPT/ALT | 60.0 percentage of participants |
| COB 20 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Albumin | 80.0 percentage of participants |
| COB 20 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Uric Acid | 20.0 percentage of participants |
| COB 20 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | SGOT/AST | 100.0 percentage of participants |
| COB 20 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Calcium | 20.0 percentage of participants |
| COB 20 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | White Blood Cell Count | 20 percentage of participants |
| COB 20 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Bilirubin | 20.0 percentage of participants |
| COB 20 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Creatinine | 100.0 percentage of participants |
| COB 20 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Sodium | 60.0 percentage of participants |
| COB 20 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Blood Glucose, Fasting | 100.0 percentage of participants |
| COB 20 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Alkaline Phosphatase | 80.0 percentage of participants |
| COB 20 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Gamma Glutamyl Transferase | 60.0 percentage of participants |
| COB 20 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Potassium | 40.0 percentage of participants |
| COB 20 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Platelets | 20.0 percentage of participants |
| COB 20 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Hemoglobin | 60.0 percentage of participants |
| COB 40 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Blood Glucose, Fasting | 100.0 percentage of participants |
| COB 40 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Platelets | 33.3 percentage of participants |
| COB 40 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | SGOT/AST | 66.7 percentage of participants |
| COB 40 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Potassium | 66.7 percentage of participants |
| COB 40 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | SGPT/ALT | 0.0 percentage of participants |
| COB 40 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Hemoglobin | 66.7 percentage of participants |
| COB 40 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Gamma Glutamyl Transferase | 66.7 percentage of participants |
| COB 40 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Alkaline Phosphatase | 66.7 percentage of participants |
| COB 40 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Phosphorus | 0.0 percentage of participants |
| COB 40 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Magnesium | 66.6 percentage of participants |
| COB 40 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Uric Acid | 0.0 percentage of participants |
| COB 40 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Calcium | 33.3 percentage of participants |
| COB 40 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Lymphocytes, Absolute | 33.3 percentage of participants |
| COB 40 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Creatinine | 100.0 percentage of participants |
| COB 40 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Bilirubin | 0.0 percentage of participants |
| COB 40 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Sodium | 33.3 percentage of participants |
| COB 40 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Glucose | 0.0 percentage of participants |
| COB 40 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | White Blood Cell Count | 0.0 percentage of participants |
| COB 40 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Albumin | 66.7 percentage of participants |
| COB 80 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Bilirubin | 0.0 percentage of participants |
| COB 80 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Albumin | 100.0 percentage of participants |
| COB 80 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Alkaline Phosphatase | 80.0 percentage of participants |
| COB 80 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | SGPT/ALT | 60.0 percentage of participants |
| COB 80 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | SGOT/AST | 60.0 percentage of participants |
| COB 80 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Calcium | 80.0 percentage of participants |
| COB 80 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Creatinine | 100.0 percentage of participants |
| COB 80 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Blood Glucose, Fasting | 0.0 percentage of participants |
| COB 80 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Gamma Glutamyl Transferase | 60.0 percentage of participants |
| COB 80 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Glucose | 0.0 percentage of participants |
| COB 80 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Hemoglobin | 100.0 percentage of participants |
| COB 80 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Lymphocytes, Absolute | 60.0 percentage of participants |
| COB 80 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Magnesium | 20.0 percentage of participants |
| COB 80 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Phosphorus | 0.0 percentage of participants |
| COB 80 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Platelets | 40.0 percentage of participants |
| COB 80 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Potassium | 40.0 percentage of participants |
| COB 80 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Sodium | 0.0 percentage of participants |
| COB 80 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Uric Acid | 0.0 percentage of participants |
| COB 80 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | White Blood Cell Count | 20.0 percentage of participants |
| COB 80 mg + GDC 400 mg | Percentage of Participants With Laboratory Abnormalities | Phosphorus | 25.0 percentage of participants |
| COB 80 mg + GDC 400 mg | Percentage of Participants With Laboratory Abnormalities | Hemoglobin | 75.0 percentage of participants |
| COB 80 mg + GDC 400 mg | Percentage of Participants With Laboratory Abnormalities | Glucose | 0.0 percentage of participants |
| COB 80 mg + GDC 400 mg | Percentage of Participants With Laboratory Abnormalities | Platelets | 50.0 percentage of participants |
| COB 80 mg + GDC 400 mg | Percentage of Participants With Laboratory Abnormalities | Gamma Glutamyl Transferase | 75.0 percentage of participants |
| COB 80 mg + GDC 400 mg | Percentage of Participants With Laboratory Abnormalities | Albumin | 100.0 percentage of participants |
| COB 80 mg + GDC 400 mg | Percentage of Participants With Laboratory Abnormalities | Potassium | 25.0 percentage of participants |
| COB 80 mg + GDC 400 mg | Percentage of Participants With Laboratory Abnormalities | Blood Glucose, Fasting | 66.6 percentage of participants |
| COB 80 mg + GDC 400 mg | Percentage of Participants With Laboratory Abnormalities | Creatinine | 100.0 percentage of participants |
| COB 80 mg + GDC 400 mg | Percentage of Participants With Laboratory Abnormalities | Sodium | 50.0 percentage of participants |
| COB 80 mg + GDC 400 mg | Percentage of Participants With Laboratory Abnormalities | Calcium | 100.0 percentage of participants |
| COB 80 mg + GDC 400 mg | Percentage of Participants With Laboratory Abnormalities | SGOT/AST | 75.0 percentage of participants |
| COB 80 mg + GDC 400 mg | Percentage of Participants With Laboratory Abnormalities | Bilirubin | 25.0 percentage of participants |
| COB 80 mg + GDC 400 mg | Percentage of Participants With Laboratory Abnormalities | SGPT/ALT | 25.0 percentage of participants |
| COB 80 mg + GDC 400 mg | Percentage of Participants With Laboratory Abnormalities | White Blood Cell Count | 25.0 percentage of participants |
| COB 80 mg + GDC 400 mg | Percentage of Participants With Laboratory Abnormalities | Uric Acid | 25.0 percentage of participants |
| COB 80 mg + GDC 400 mg | Percentage of Participants With Laboratory Abnormalities | Magnesium | 50.0 percentage of participants |
| COB 80 mg + GDC 400 mg | Percentage of Participants With Laboratory Abnormalities | Lymphocytes, Absolute | 50.0 percentage of participants |
| COB 80 mg + GDC 400 mg | Percentage of Participants With Laboratory Abnormalities | Alkaline Phosphatase | 75.0 percentage of participants |
| COB 100 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Sodium | 16.7 percentage of participants |
| COB 100 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Phosphorus | 0.0 percentage of participants |
| COB 100 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Calcium | 33.3 percentage of participants |
| COB 100 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Glucose | 0.0 percentage of participants |
| COB 100 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Magnesium | 16.7 percentage of participants |
| COB 100 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Albumin | 83.3 percentage of participants |
| COB 100 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | SGOT/AST | 50.0 percentage of participants |
| COB 100 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Platelets | 33.3 percentage of participants |
| COB 100 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Gamma Glutamyl Transferase | 50.0 percentage of participants |
| COB 100 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Lymphocytes, Absolute | 16.7 percentage of participants |
| COB 100 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Blood Glucose, Fasting | 100.0 percentage of participants |
| COB 100 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Uric Acid | 16.7 percentage of participants |
| COB 100 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Bilirubin | 0.0 percentage of participants |
| COB 100 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Potassium | 33.3 percentage of participants |
| COB 100 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | SGPT/ALT | 33.3 percentage of participants |
| COB 100 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Creatinine | 50.0 percentage of participants |
| COB 100 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Hemoglobin | 66.7 percentage of participants |
| COB 100 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | White Blood Cell Count | 33.3 percentage of participants |
| COB 100 mg + GDC 200 mg | Percentage of Participants With Laboratory Abnormalities | Alkaline Phosphatase | 50.0 percentage of participants |
Secondary
Change From Baseline in Fluorodeoxyglucose Positron Emission Tomography (FDG-PET)
Time frame: Baseline, Day 15
Population: Data for this measure were not collected.
Secondary
Change From Baseline in Tumor Tissue Biomarkers
Time frame: Up to 15 months
Population: Data for this measure were not collected.
Secondary
Maximum Serum Concentration (Cmax) for Cobimetinib
Time frame: Up to Day 22
Population: Data are reported for evaluable participants.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Not Assigned | Maximum Serum Concentration (Cmax) for Cobimetinib | Steady State | 73.0 nanograms per milliliter (ng/mL) | — |
| COB 20 mg + GDC 200 mg | Maximum Serum Concentration (Cmax) for Cobimetinib | Day 1 | 41.8 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 102 |
| COB 20 mg + GDC 200 mg | Maximum Serum Concentration (Cmax) for Cobimetinib | Steady State | 48.5 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 121 |
| COB 40 mg + GDC 200 mg | Maximum Serum Concentration (Cmax) for Cobimetinib | Day 1 | 90.2 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 60.9 |
| COB 40 mg + GDC 200 mg | Maximum Serum Concentration (Cmax) for Cobimetinib | Steady State | 204 nanograms per milliliter (ng/mL) | — |
| COB 80 mg + GDC 200 mg | Maximum Serum Concentration (Cmax) for Cobimetinib | Day 1 | 392 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 31.9 |
| COB 80 mg + GDC 200 mg | Maximum Serum Concentration (Cmax) for Cobimetinib | Steady State | 399 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 46.4 |
| COB 80 mg + GDC 400 mg | Maximum Serum Concentration (Cmax) for Cobimetinib | Day 1 | 155 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 52.5 |
| COB 80 mg + GDC 400 mg | Maximum Serum Concentration (Cmax) for Cobimetinib | Steady State | 284 nanograms per milliliter (ng/mL) | — |
| COB 100 mg + GDC 200 mg | Maximum Serum Concentration (Cmax) for Cobimetinib | Day 1 | 384 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 53.2 |
| COB 100 mg + GDC 200 mg | Maximum Serum Concentration (Cmax) for Cobimetinib | Steady State | 431 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 63.3 |
Secondary
Maximum Serum Concentration (Cmax) for GDC-0994
Time frame: Up to Day 22
Population: Data are reported for evaluable participants.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Not Assigned | Maximum Serum Concentration (Cmax) for GDC-0994 | Steady State | 2.56 micromoles | — |
| COB 20 mg + GDC 200 mg | Maximum Serum Concentration (Cmax) for GDC-0994 | Day 1 | 2.51 micromoles | Geometric Coefficient of Variation 54.6 |
| COB 20 mg + GDC 200 mg | Maximum Serum Concentration (Cmax) for GDC-0994 | Steady State | 1.80 micromoles | Geometric Coefficient of Variation 74.2 |
| COB 40 mg + GDC 200 mg | Maximum Serum Concentration (Cmax) for GDC-0994 | Day 1 | 2.08 micromoles | Geometric Coefficient of Variation 68.4 |
| COB 40 mg + GDC 200 mg | Maximum Serum Concentration (Cmax) for GDC-0994 | Steady State | 2.01 micromoles | Geometric Coefficient of Variation 0 |
| COB 80 mg + GDC 200 mg | Maximum Serum Concentration (Cmax) for GDC-0994 | Day 1 | 2.02 micromoles | Geometric Coefficient of Variation 109 |
| COB 80 mg + GDC 200 mg | Maximum Serum Concentration (Cmax) for GDC-0994 | Steady State | 2.26 micromoles | Geometric Coefficient of Variation 23.1 |
| COB 80 mg + GDC 400 mg | Maximum Serum Concentration (Cmax) for GDC-0994 | Day 1 | 2.42 micromoles | Geometric Coefficient of Variation 33.6 |
| COB 80 mg + GDC 400 mg | Maximum Serum Concentration (Cmax) for GDC-0994 | Steady State | 2.09 micromoles | Geometric Coefficient of Variation 0 |
| COB 100 mg + GDC 200 mg | Maximum Serum Concentration (Cmax) for GDC-0994 | Day 1 | 2.56 micromoles | Geometric Coefficient of Variation 77.8 |
| COB 100 mg + GDC 200 mg | Maximum Serum Concentration (Cmax) for GDC-0994 | Steady State | 2.36 micromoles | Geometric Coefficient of Variation 28.2 |
Secondary
Mean Accumulation Ratio
Time frame: 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
Population: Data for this measure were not collected.
Secondary
Mean Terminal Half-life (t1/2)
Time frame: Up to day 22 of study
Population: Data for this measure were not collected.
Secondary
Median Time to Maximum Serum Concentration (Tmax) for Cobimetinib
Time frame: Up to Day 22
Population: Data are reported for evaluable participants.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Not Assigned | Median Time to Maximum Serum Concentration (Tmax) for Cobimetinib | Steady State | 1.00 hours |
| COB 20 mg + GDC 200 mg | Median Time to Maximum Serum Concentration (Tmax) for Cobimetinib | Day 1 | 2.00 hours |
| COB 20 mg + GDC 200 mg | Median Time to Maximum Serum Concentration (Tmax) for Cobimetinib | Steady State | 1.50 hours |
| COB 40 mg + GDC 200 mg | Median Time to Maximum Serum Concentration (Tmax) for Cobimetinib | Day 1 | 2.00 hours |
| COB 40 mg + GDC 200 mg | Median Time to Maximum Serum Concentration (Tmax) for Cobimetinib | Steady State | 24.0 hours |
| COB 80 mg + GDC 200 mg | Median Time to Maximum Serum Concentration (Tmax) for Cobimetinib | Steady State | 1.00 hours |
| COB 80 mg + GDC 200 mg | Median Time to Maximum Serum Concentration (Tmax) for Cobimetinib | Day 1 | 2.00 hours |
| COB 80 mg + GDC 400 mg | Median Time to Maximum Serum Concentration (Tmax) for Cobimetinib | Day 1 | 4.00 hours |
| COB 80 mg + GDC 400 mg | Median Time to Maximum Serum Concentration (Tmax) for Cobimetinib | Steady State | 2.00 hours |
| COB 100 mg + GDC 200 mg | Median Time to Maximum Serum Concentration (Tmax) for Cobimetinib | Steady State | 2.00 hours |
| COB 100 mg + GDC 200 mg | Median Time to Maximum Serum Concentration (Tmax) for Cobimetinib | Day 1 | 2.00 hours |
Secondary
Median Time to Maximum Serum Concentration (Tmax) for GDC-0994
Time frame: Up to Day 22
Population: Data are reported for evaluable participants.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Not Assigned | Median Time to Maximum Serum Concentration (Tmax) for GDC-0994 | Steady State | 3.00 hours |
| COB 20 mg + GDC 200 mg | Median Time to Maximum Serum Concentration (Tmax) for GDC-0994 | Day 1 | 4.00 hours |
| COB 20 mg + GDC 200 mg | Median Time to Maximum Serum Concentration (Tmax) for GDC-0994 | Steady State | 3.00 hours |
| COB 40 mg + GDC 200 mg | Median Time to Maximum Serum Concentration (Tmax) for GDC-0994 | Day 1 | 6.00 hours |
| COB 40 mg + GDC 200 mg | Median Time to Maximum Serum Concentration (Tmax) for GDC-0994 | Steady State | 24.0 hours |
| COB 80 mg + GDC 200 mg | Median Time to Maximum Serum Concentration (Tmax) for GDC-0994 | Steady State | 2.00 hours |
| COB 80 mg + GDC 200 mg | Median Time to Maximum Serum Concentration (Tmax) for GDC-0994 | Day 1 | 3.00 hours |
| COB 80 mg + GDC 400 mg | Median Time to Maximum Serum Concentration (Tmax) for GDC-0994 | Day 1 | 15.0 hours |
| COB 80 mg + GDC 400 mg | Median Time to Maximum Serum Concentration (Tmax) for GDC-0994 | Steady State | 3.00 hours |
| COB 100 mg + GDC 200 mg | Median Time to Maximum Serum Concentration (Tmax) for GDC-0994 | Day 1 | 2.50 hours |
| COB 100 mg + GDC 200 mg | Median Time to Maximum Serum Concentration (Tmax) for GDC-0994 | Steady State | 2.00 hours |
Secondary
Total Exposure (AUC From Time 0 to 24 Hour After Dose) for Cobimetinib
Time frame: 0 to 24 hours post-dose (Up to Day 22)
Population: Data are reported for evaluable participants.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Not Assigned | Total Exposure (AUC From Time 0 to 24 Hour After Dose) for Cobimetinib | Steady State | 908 ng x hr/mL | — |
| COB 20 mg + GDC 200 mg | Total Exposure (AUC From Time 0 to 24 Hour After Dose) for Cobimetinib | Steady State | 508 ng x hr/mL | Geometric Coefficient of Variation 255 |
| COB 20 mg + GDC 200 mg | Total Exposure (AUC From Time 0 to 24 Hour After Dose) for Cobimetinib | Day 1 | 501 ng x hr/mL | Geometric Coefficient of Variation 121 |
| COB 40 mg + GDC 200 mg | Total Exposure (AUC From Time 0 to 24 Hour After Dose) for Cobimetinib | Day 1 | 1020 ng x hr/mL | Geometric Coefficient of Variation 33.9 |
| COB 40 mg + GDC 200 mg | Total Exposure (AUC From Time 0 to 24 Hour After Dose) for Cobimetinib | Steady State | 2460 ng x hr/mL | — |
| COB 80 mg + GDC 200 mg | Total Exposure (AUC From Time 0 to 24 Hour After Dose) for Cobimetinib | Steady State | 4320 ng x hr/mL | Geometric Coefficient of Variation 37.4 |
| COB 80 mg + GDC 200 mg | Total Exposure (AUC From Time 0 to 24 Hour After Dose) for Cobimetinib | Day 1 | 4420 ng x hr/mL | Geometric Coefficient of Variation 25.5 |
| COB 80 mg + GDC 400 mg | Total Exposure (AUC From Time 0 to 24 Hour After Dose) for Cobimetinib | Day 1 | 2460 ng x hr/mL | Geometric Coefficient of Variation 50.9 |
| COB 80 mg + GDC 400 mg | Total Exposure (AUC From Time 0 to 24 Hour After Dose) for Cobimetinib | Steady State | 3410 ng x hr/mL | — |
| COB 100 mg + GDC 200 mg | Total Exposure (AUC From Time 0 to 24 Hour After Dose) for Cobimetinib | Day 1 | 4060 ng x hr/mL | Geometric Coefficient of Variation 74.3 |
| COB 100 mg + GDC 200 mg | Total Exposure (AUC From Time 0 to 24 Hour After Dose) for Cobimetinib | Steady State | 4070 ng x hr/mL | — |
Secondary
Total Exposure (AUC From Time 0 to 24 Hour After Dose) for GDC-0994
Data are reported for evaluable participants.
Time frame: 0 to 24 hours post-dose (Up to Day 22)
Population: Data are reported for evaluable participants.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Not Assigned | Total Exposure (AUC From Time 0 to 24 Hour After Dose) for GDC-0994 | Steady State | 48.3 hr x microM | — |
| COB 20 mg + GDC 200 mg | Total Exposure (AUC From Time 0 to 24 Hour After Dose) for GDC-0994 | Day 1 | 37.0 hr x microM | Geometric Coefficient of Variation 45.9 |
| COB 20 mg + GDC 200 mg | Total Exposure (AUC From Time 0 to 24 Hour After Dose) for GDC-0994 | Steady State | 23.5 hr x microM | Geometric Coefficient of Variation 73.4 |
| COB 40 mg + GDC 200 mg | Total Exposure (AUC From Time 0 to 24 Hour After Dose) for GDC-0994 | Day 1 | 32.9 hr x microM | Geometric Coefficient of Variation 55.4 |
| COB 40 mg + GDC 200 mg | Total Exposure (AUC From Time 0 to 24 Hour After Dose) for GDC-0994 | Steady State | 24.1 hr x microM | — |
| COB 80 mg + GDC 200 mg | Total Exposure (AUC From Time 0 to 24 Hour After Dose) for GDC-0994 | Day 1 | 27.9 hr x microM | Geometric Coefficient of Variation 93.8 |
| COB 80 mg + GDC 200 mg | Total Exposure (AUC From Time 0 to 24 Hour After Dose) for GDC-0994 | Steady State | 33.3 hr x microM | Geometric Coefficient of Variation 66.4 |
| COB 80 mg + GDC 400 mg | Total Exposure (AUC From Time 0 to 24 Hour After Dose) for GDC-0994 | Day 1 | 37.8 hr x microM | Geometric Coefficient of Variation 37.5 |
| COB 80 mg + GDC 400 mg | Total Exposure (AUC From Time 0 to 24 Hour After Dose) for GDC-0994 | Steady State | 37.2 hr x microM | — |
| COB 100 mg + GDC 200 mg | Total Exposure (AUC From Time 0 to 24 Hour After Dose) for GDC-0994 | Day 1 | 37.7 hr x microM | Geometric Coefficient of Variation 81 |
| COB 100 mg + GDC 200 mg | Total Exposure (AUC From Time 0 to 24 Hour After Dose) for GDC-0994 | Steady State | 34.0 hr x microM | — |