Neoplasms
Conditions
Keywords
GDC0973, MEK, MEK inhibitor, GDC0068, Akt, Akt inhibitor
Brief summary
This open-label, multicenter, Phase Ib dose-escalation study will evaluate the safety, tolerability and pharmacokinetics of oral dosing of GDC-0973 and GDC-0068 administered in combination in patients with locally advanced or metastatic solid tumors. Cohorts of patients will receive multiple ascending doses of GDC-0973 and GDC-0068. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.
Interventions
DRUGIpatasertib
multiple doses
DRUGCobimetinib
multiple doses
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
* Histologically or cytologically documented locally advanced or metastatic solid tumors for which standard therapies either do not exist or have proven ineffective or intolerable * Evaluable disease or disease measurable per Response Evaluation Criteria in Solid Tumors (RECIST) * Life expectancy \>/= 12 weeks * Adequate hematologic and end organ function
Exclusion criteria
* History of prior significant toxicity from another MEK pathway inhibitor requiring discontinuation of treatment * History of prior significant toxicity from another phosphoinositide 3-kinase (PI3K) or Akt pathway or mammalian target of rapamycin (mTOR) inhibitor requiring discontinuation of treatment * Anti-cancer therapy within 28 days prior to first dose of study drug, except as stated in protocol * History of type I or type II diabetes mellitus requiring insulin * Current severe, uncontrolled systemic disease (e.g. clinically significant cardiovascular, pulmonary, or metabolic disease) * Clinically significant history of liver disease, current alcohol abuse, or current known active infection with HIV, hepatitis B or hepatitis C virus * Active autoimmune disease * Pregnant or lactating women * Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms * History of glaucoma * History of retinal vein occlusion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities (DLTs) | Cycle 1 (28 Days) | DLT is defined as 1 of the following toxicities considered by the investigator to be possibly related to study drugs: a) Grade (G) ≥3 febrile neutropenia, b) G ≥4 neutropenia (absolute neutrophil count \[ANC\] \<500/ microliter \[μL\]) lasting \>5 days , c) G ≥4 thrombocytopenia lasting \>2 days, d) G ≥4 anemia, e) G ≥3 elevation of total bilirubin or hepatic transaminase or alkaline phosphatase (ALP) lasting \>3 days, f) Hepatic transaminases \>3 × Upper Limit of Normal (ULN) and an increase in total bilirubin \>2 × ULN without any findings of cholestasis and in the absence of other contributory factors, g) G ≥2 visual changes that do not resolve to baseline within 14 days, h) 1 episode of fasting G 4 hyperglycemia or 3 episodes of fasting, i) G 3 hyperglycemia on separate days within 7 days, j) G ≥4 fasting hypercholesterolemia or triglyceridemia for ≥2 weeks, k) G ≥3 nausea, vomiting, or diarrhea despite maximal supportive medications lasting for ≥3 days. |
| Number of DLTs Categorized as Per the Nature | Cycle 1 (28 Days) | DLT is defined as 1 of the following toxicities considered by the investigator to be possibly related to study drugs: a) G ≥3 febrile neutropenia, b) G ≥4 neutropenia (ANC \<500/μL) lasting \>5 days , c) G ≥4 thrombocytopenia lasting \>2 days, d) G ≥4 anemia, e) G ≥3 elevation of total bilirubin or hepatic transaminase or ALP lasting \>3 days, f) Hepatic transaminases \>3 × ULN and an increase in total bilirubin \>2 × ULN without any findings of cholestasis and in the absence of other contributory factors, g) G ≥2 visual changes that do not resolve to baseline within 14 days, h) 1 episode of fasting G 4 hyperglycemia or 3 episodes of fasting, i) G 3 hyperglycemia on separate days within 7 days, j) G ≥4 fasting hypercholesterolemia or triglyceridemia for ≥2 weeks, k) G ≥3 nausea, vomiting, or diarrhea despite maximal supportive medications lasting for ≥3 days. Hematologic, Hepatic and non-hematologic and non-hepatic DLT categories were to be reported. |
| Maximum Tolerated Doses (MTDs) in Combination of Cobimetinib and Ipatasertib During Dose-Escalation Stage 1 | Cycle 1 (28 Days) | An adverse event (AE) is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution. On the basis of AEs that did not meet protocol-defined DLT criteria (defined in Outcome measure 1) but indicated intolerability of a given dose combination, the combination MTDs were determined (as per investigator) during Stage 1 of the study. |
| Number of Participants With At Least One AE Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version (V) 4.0 | From Baseline up to 30 days after the last dose of study treatment or until initiation of another anticancer treatment whichever occurred first (Up to 33 months) | AE was defined in Outcome Measure 3. AEs were graded as per NCI CTCAE V 4.0 as follows: G 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; G 2: minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily living (ADL) (instrumental ADL refers to preparing meals, shopping for groceries or clothes, using the telephone, managing money and others); G 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated, disabling, limiting self care ADL (refers to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden); G 4: Life-threatening consequences, urgent intervention indicated; G 5: Death related to AE. If a participant had multiple events of different grades, the highest grade that occurred in that participant was counted. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Objective Response of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | Screening, Days 21-28 of Cycle 2, Day 25 (± 3 days) of Cycle 4 and every 8 weeks thereafter till study completion (Up to 33 months) | RECIST v1.1 (for measurable disease), CR: disappearance of all target lesions, reduction in short axis \<10 millimeters in pathological lymph nodes (target and non-target lesions); PR: at least a 30 percent (%) decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. Responses were confirmed by repeat assessments ≥4 weeks after initial documentation. |
| Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Predose (0 hour), 1, 2, 4, 6 and 24 hours postdose on Day 1 and Day 15 of Cycle 1 | — |
| Progression-Free Survival (PFS) Time for Participants With Measurable Disease According to RECIST v1.1 | Screening, Days 21-28 of Cycle 2, Day 25 (± 3 days) of Cycle 4 and every 8 weeks thereafter till study completion (Up to 33 months) | PFS is defined as the time from study treatment initiation to the first occurrence of disease progression, as determined by investigator review of tumor assessments using RECIST 1.1, or death from any cause during the study (i.e., within 30 days after the last dose of study treatment). |
| Duration of Objective Response for Participants With Measurable Disease According to RECIST v1.1 | Screening, Days 21-28 of Cycle 2, Day 25 (± 3 days) of Cycle 4 and every 8 weeks thereafter till study completion (Up to 33 months) | Duration of response, defined as the time from first occurrence of a documented objective response until the time of disease progression, as determined by investigator review of tumor assessments using RECIST 1.1, or death from any cause during the study (i.e., within 30 days after the last dose of study treatment). |
| Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Predose (0 hour), 1, 2, 4, 6 and 24 hours postdose on Day 1 and Day 15 of Cycle 1 | — |
| Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Predose (0 hour), 1, 2, 4, 6 and 24 hours postdose on Day 1 and Day 15 of Cycle 1 | — |
| Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Predose (0 hour), 1, 2, 4, 6 and 24 hours postdose on Day 1 and Day 15 of Cycle 1 | — |
Countries
Spain, United States
Participant flow
Pre-assignment details
Study included two stages. Stage 1: dose escalation cohorts (DEC), consisted of Arm A (concurrent 21 day dosing followed by 7 day dosing holiday) and Arm B (intermittent dosing). Stage 2: indication specific expansion cohorts (PTEN-low endometrial carcinoma and PTEN-low triple-negative breast cancer) treated with recommended phase 2 dose.
Participants by arm
| Arm | Count |
|---|---|
| DEC Arm A: 40 mg Cobimetinib + 200 mg Ipatasertib Participants received oral 40 mg cobimetinib and 200 mg ipatasertib concurrently once daily on Days 1-21, with a 7-day dosing holiday on Days 22-28, every 28 days (1 Cycle=28 Days) until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. | 3 |
| DEC Arm A: 60 mg Cobimetinib + 200 mg Ipatasertib Participants received oral 60 mg cobimetinib and 200 mg ipatasertib concurrently once daily on Days 1-21, with a 7-day dosing holiday on Days 22-28, every 28 days (1 Cycle=28 Days) until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. | 7 |
| DEC Arm A: 60 mg Cobimetinib + 300 mg Ipatasertib Participants received oral 60 mg cobimetinib and 300 mg ipatasertib concurrently once daily on Days 1-21, with a 7-day dosing holiday on Days 22-28, every 28 days (1 Cycle=28 Days) until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. | 3 |
| DEC Arm A: 40 mg Cobimetinib + 400 mg Ipatasertib Participants received oral 40 mg cobimetinib and 400 mg ipatasertib concurrently once daily on Days 1-21, with a 7-day dosing holiday on Days 22-28, every 28 days (1 Cycle=28 Days) until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. | 4 |
| DEC Arm B: 100 mg Cobimetinib + 200 mg Ipatasertib Participants received oral 200 mg ipatasertib once daily on Days 1-21 consecutively with concurrent dosing of 100 mg cobimetinib on Days 1, 4, 8, 11, 15, and 18 with a 7-day dosing holiday on Days 22-28, every 28 days (1 Cycle=28 Days) until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. | 4 |
| DEC Arm B: 125 mg Cobimetinib + 200 mg Ipatasertib Participants received oral 200 mg ipatasertib once daily on Days 1-21 consecutively with concurrent dosing of 125 mg cobimetinib on Days 1, 4, 8, 11, 15, and 18 with a 7-day dosing holiday on Days 22-28, every 28 days (1 Cycle=28 Days) until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. | 4 |
| DEC Arm B: 125 mg Cobimetinib + 400 mg Ipatasertib Participants received oral 400 mg ipatasertib once daily on Days 1-21 consecutively with concurrent dosing of 125 mg cobimetinib on Days 1, 4, 8, 11, 15, and 18 with a 7-day dosing holiday on Days 22-28, every 28 days (1 Cycle=28 Days) until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. | 3 |
| DEC Arm B: 150 mg Cobimetinib + 300 mg Ipatasertib Participants received oral 300 mg ipatasertib once daily on Days 1-21 consecutively with concurrent dosing of 150 mg cobimetinib on Days 1, 4, 8, 11, 15, and 18 with a 7-day dosing holiday on Days 22-28, every 28 days (1 Cycle=28 Days) until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. | 7 |
| DEC Arm B: 175 mg Cobimetinib + 200 mg Ipatasertib Participants received oral 200 mg ipatasertib once daily on Days 1-21 consecutively with concurrent dosing of 175 mg cobimetinib on Days 1, 4, 8, 11, 15, and 18 with a 7-day dosing holiday on Days 22-28, every 28 days (1 Cycle=28 Days) until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. | 3 |
| DEC Arm B: 150 mg Cobimetinib + 200 mg Ipatasertib Participants received oral 200 mg ipatasertib once daily on Days 1-21 consecutively with concurrent dosing of 150 mg cobimetinib on Days 1, 4, 8, 11, 15, and 18 with a 7-day dosing holiday on Days 22-28, every 28 days (1 Cycle=28 Days) until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. | 7 |
| DEC Arm B: 100 mg Cobimetinib + 400 mg Ipatasertib Participants received oral 400 mg ipatasertib once daily on Days 1-21 consecutively with concurrent dosing of 100 mg cobimetinib on Days 1, 4, 8, 11, 15, and 18 with a 7-day dosing holiday on Days 22-28, every 28 days (1 Cycle=28 Days) until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. | 3 |
| Endometrial Carcinoma: 140 mg Cobimetinib + 300 mg Ipatasertib Participants with endometrial carcinoma received oral 300 mg ipatasertib once daily on Days 1-21 consecutively with concurrent dosing of 140 mg cobimetinib on Days 1, 4, 8, 11, 15, and 18 with a 7-day dosing holiday on Days 22-28, every 28 days (1 Cycle=28 Days) until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. | 14 |
| Breast Cancer: 140 mg Cobimetinib + 300 mg Ipatasertib Participants with triple negative breast cancer received oral 300 mg ipatasertib once daily on Days 1-21 consecutively with concurrent dosing of 140 mg cobimetinib on Days 1, 4, 8, 11, 15, and 18 with a 7-day dosing holiday on Days 22-28, every 28 days (1 Cycle=28 Days) until disease progression, unacceptable toxicity, or any other discontinuation criteria were met. | 5 |
| Total | 67 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Stage 1 | Adverse Event | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Stage 1 | Death | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Stage 1 | Non Compliance | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Stage 1 | Physician Decision | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 |
| Stage 1 | Progression of Disease | 2 | 6 | 2 | 1 | 2 | 4 | 1 | 7 | 2 | 5 | 3 | 0 | 0 |
| Stage 1 | Withdrawal by Subject | 0 | 1 | 0 | 2 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 |
| Stage 2 | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 1 |
| Stage 2 | Progression of Disease | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 12 | 4 |
Baseline characteristics
| Characteristic | DEC Arm B: 100 mg Cobimetinib + 200 mg Ipatasertib | DEC Arm B: 125 mg Cobimetinib + 200 mg Ipatasertib | DEC Arm A: 40 mg Cobimetinib + 200 mg Ipatasertib | DEC Arm A: 60 mg Cobimetinib + 200 mg Ipatasertib | DEC Arm A: 60 mg Cobimetinib + 300 mg Ipatasertib | DEC Arm A: 40 mg Cobimetinib + 400 mg Ipatasertib | DEC Arm B: 125 mg Cobimetinib + 400 mg Ipatasertib | DEC Arm B: 150 mg Cobimetinib + 300 mg Ipatasertib | DEC Arm B: 175 mg Cobimetinib + 200 mg Ipatasertib | DEC Arm B: 150 mg Cobimetinib + 200 mg Ipatasertib | DEC Arm B: 100 mg Cobimetinib + 400 mg Ipatasertib | Endometrial Carcinoma: 140 mg Cobimetinib + 300 mg Ipatasertib | Breast Cancer: 140 mg Cobimetinib + 300 mg Ipatasertib | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 62.3 years STANDARD_DEVIATION 7 | 51.8 years STANDARD_DEVIATION 10.9 | 61.0 years STANDARD_DEVIATION 3.5 | 59.1 years STANDARD_DEVIATION 8.7 | 58.3 years STANDARD_DEVIATION 5.5 | 66.8 years STANDARD_DEVIATION 16.5 | 59.0 years STANDARD_DEVIATION 9.2 | 58.6 years STANDARD_DEVIATION 11.9 | 61.0 years STANDARD_DEVIATION 13.7 | 57.6 years STANDARD_DEVIATION 10.9 | 52.7 years STANDARD_DEVIATION 24.9 | 62.9 years STANDARD_DEVIATION 8.7 | 49.0 years STANDARD_DEVIATION 10.1 | 59.0 years STANDARD_DEVIATION 11 |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 2 Participants | 4 Participants | 1 Participants | 3 Participants | 2 Participants | 3 Participants | 2 Participants | 4 Participants | 1 Participants | 14 Participants | 5 Participants | 48 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 1 Participants | 3 Participants | 2 Participants | 1 Participants | 1 Participants | 4 Participants | 1 Participants | 3 Participants | 2 Participants | 0 Participants | 0 Participants | 19 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 | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 7 / 7 | 3 / 3 | 4 / 4 | 4 / 4 | 4 / 4 | 3 / 3 | 7 / 7 | 3 / 3 | 6 / 6 | 3 / 3 | 14 / 14 | 5 / 5 |
| serious Total, serious adverse events | 1 / 3 | 2 / 7 | 0 / 3 | 2 / 4 | 1 / 4 | 3 / 4 | 1 / 3 | 1 / 7 | 0 / 3 | 2 / 6 | 2 / 3 | 10 / 14 | 2 / 5 |
Outcome results
Primary
Maximum Tolerated Doses (MTDs) in Combination of Cobimetinib and Ipatasertib During Dose-Escalation Stage 1
An adverse event (AE) is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution. On the basis of AEs that did not meet protocol-defined DLT criteria (defined in Outcome measure 1) but indicated intolerability of a given dose combination, the combination MTDs were determined (as per investigator) during Stage 1 of the study.
Time frame: Cycle 1 (28 Days)
Population: Safety analysis population participants from dose escalation cohorts.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DEC Arm A: 40 mg Cobimetinib + 200 mg Ipatasertib | Maximum Tolerated Doses (MTDs) in Combination of Cobimetinib and Ipatasertib During Dose-Escalation Stage 1 | Arm B Ipatasertib dose | 300 milligrams |
| DEC Arm A: 40 mg Cobimetinib + 200 mg Ipatasertib | Maximum Tolerated Doses (MTDs) in Combination of Cobimetinib and Ipatasertib During Dose-Escalation Stage 1 | Arm A Cobimetinib dose | 60 milligrams |
| DEC Arm A: 40 mg Cobimetinib + 200 mg Ipatasertib | Maximum Tolerated Doses (MTDs) in Combination of Cobimetinib and Ipatasertib During Dose-Escalation Stage 1 | Arm A Ipatasertib dose | 200 milligrams |
| DEC Arm A: 40 mg Cobimetinib + 200 mg Ipatasertib | Maximum Tolerated Doses (MTDs) in Combination of Cobimetinib and Ipatasertib During Dose-Escalation Stage 1 | Arm B Cobimetinib dose | 150 milligrams |
Primary
Number of DLTs Categorized as Per the Nature
DLT is defined as 1 of the following toxicities considered by the investigator to be possibly related to study drugs: a) G ≥3 febrile neutropenia, b) G ≥4 neutropenia (ANC \<500/μL) lasting \>5 days , c) G ≥4 thrombocytopenia lasting \>2 days, d) G ≥4 anemia, e) G ≥3 elevation of total bilirubin or hepatic transaminase or ALP lasting \>3 days, f) Hepatic transaminases \>3 × ULN and an increase in total bilirubin \>2 × ULN without any findings of cholestasis and in the absence of other contributory factors, g) G ≥2 visual changes that do not resolve to baseline within 14 days, h) 1 episode of fasting G 4 hyperglycemia or 3 episodes of fasting, i) G 3 hyperglycemia on separate days within 7 days, j) G ≥4 fasting hypercholesterolemia or triglyceridemia for ≥2 weeks, k) G ≥3 nausea, vomiting, or diarrhea despite maximal supportive medications lasting for ≥3 days. Hematologic, Hepatic and non-hematologic and non-hepatic DLT categories were to be reported.
Time frame: Cycle 1 (28 Days)
Population: Data for this outcome measure was not analyzed as no participant experienced DLT.
Primary
Number of Participants With At Least One AE Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version (V) 4.0
AE was defined in Outcome Measure 3. AEs were graded as per NCI CTCAE V 4.0 as follows: G 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; G 2: minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily living (ADL) (instrumental ADL refers to preparing meals, shopping for groceries or clothes, using the telephone, managing money and others); G 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated, disabling, limiting self care ADL (refers to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden); G 4: Life-threatening consequences, urgent intervention indicated; G 5: Death related to AE. If a participant had multiple events of different grades, the highest grade that occurred in that participant was counted.
Time frame: From Baseline up to 30 days after the last dose of study treatment or until initiation of another anticancer treatment whichever occurred first (Up to 33 months)
Population: Safety analysis population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DEC Arm A: 40 mg Cobimetinib + 200 mg Ipatasertib | Number of Participants With At Least One AE Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version (V) 4.0 | Grade 1 (G 1) | 4 participants |
| DEC Arm A: 40 mg Cobimetinib + 200 mg Ipatasertib | Number of Participants With At Least One AE Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version (V) 4.0 | Grade 2 (G 2) | 15 participants |
| DEC Arm A: 40 mg Cobimetinib + 200 mg Ipatasertib | Number of Participants With At Least One AE Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version (V) 4.0 | Grade 3 (G 3) | 36 participants |
| DEC Arm A: 40 mg Cobimetinib + 200 mg Ipatasertib | Number of Participants With At Least One AE Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version (V) 4.0 | Grade 4 (G 4) | 1 participants |
| DEC Arm A: 40 mg Cobimetinib + 200 mg Ipatasertib | Number of Participants With At Least One AE Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version (V) 4.0 | Grade 5 (G 5) | 10 participants |
Primary
Number of Participants With Dose Limiting Toxicities (DLTs)
DLT is defined as 1 of the following toxicities considered by the investigator to be possibly related to study drugs: a) Grade (G) ≥3 febrile neutropenia, b) G ≥4 neutropenia (absolute neutrophil count \[ANC\] \<500/ microliter \[μL\]) lasting \>5 days , c) G ≥4 thrombocytopenia lasting \>2 days, d) G ≥4 anemia, e) G ≥3 elevation of total bilirubin or hepatic transaminase or alkaline phosphatase (ALP) lasting \>3 days, f) Hepatic transaminases \>3 × Upper Limit of Normal (ULN) and an increase in total bilirubin \>2 × ULN without any findings of cholestasis and in the absence of other contributory factors, g) G ≥2 visual changes that do not resolve to baseline within 14 days, h) 1 episode of fasting G 4 hyperglycemia or 3 episodes of fasting, i) G 3 hyperglycemia on separate days within 7 days, j) G ≥4 fasting hypercholesterolemia or triglyceridemia for ≥2 weeks, k) G ≥3 nausea, vomiting, or diarrhea despite maximal supportive medications lasting for ≥3 days.
Time frame: Cycle 1 (28 Days)
Population: Safety analysis set included all participants who received at least 1 dose of study treatment. This outcome was analyzed in safety analysis population participants in dose escalation cohorts.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DEC Arm A: 40 mg Cobimetinib + 200 mg Ipatasertib | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 participants |
| DEC Arm A: 60 mg Cobimetinib + 200 mg Ipatasertib | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 participants |
| DEC Arm A: 60 mg Cobimetinib + 300 mg Ipatasertib | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 participants |
| DEC Arm A: 40 mg Cobimetinib + 400 mg Ipatasertib | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 participants |
| DEC Arm B: 100 mg Cobimetinib + 200 mg Ipatasertib | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 participants |
| DEC Arm B: 125 mg Cobimetinib + 200 mg Ipatasertib | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 participants |
| DEC Arm B: 125 mg Cobimetinib + 400 mg Ipatasertib | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 participants |
| DEC Arm B: 150 mg Cobimetinib + 300 mg Ipatasertib | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 participants |
| DEC Arm B: 175 mg Cobimetinib + 200 mg Ipatasertib | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 participants |
| DEC Arm B: 150 mg Cobimetinib + 200 mg Ipatasertib | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 participants |
| DEC Arm B: 100 mg Cobimetinib + 400 mg Ipatasertib | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 participants |
Secondary
Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15
Time frame: Predose (0 hour), 1, 2, 4, 6 and 24 hours postdose on Day 1 and Day 15 of Cycle 1
Population: Pharmacokinetic analysis population: Included all participants who received study treatment and had at least 1 cobimetinib and ipatasertib plasma concentration available. n represents the number of participants who were evaluable for that particular assessment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| DEC Arm A: 40 mg Cobimetinib + 200 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 1500 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 320 |
| DEC Arm A: 40 mg Cobimetinib + 200 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 703 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 40.8 |
| DEC Arm A: 40 mg Cobimetinib + 200 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 3250 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 223 |
| DEC Arm A: 40 mg Cobimetinib + 200 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 688 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 106 |
| DEC Arm A: 60 mg Cobimetinib + 200 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 781 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 20.7 |
| DEC Arm A: 60 mg Cobimetinib + 200 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 1130 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 68.6 |
| DEC Arm A: 60 mg Cobimetinib + 200 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 3260 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 48.6 |
| DEC Arm A: 60 mg Cobimetinib + 200 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 538 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 33.8 |
| DEC Arm A: 60 mg Cobimetinib + 300 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 5050 nanograms*hours/milliliter (ng*h/mL) | — |
| DEC Arm A: 60 mg Cobimetinib + 300 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 7080 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 91.1 |
| DEC Arm A: 60 mg Cobimetinib + 300 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 2440 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 45.2 |
| DEC Arm A: 60 mg Cobimetinib + 300 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 1760 nanograms*hours/milliliter (ng*h/mL) | — |
| DEC Arm A: 40 mg Cobimetinib + 400 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 1920 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 87.8 |
| DEC Arm A: 40 mg Cobimetinib + 400 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 2500 nanograms*hours/milliliter (ng*h/mL) | — |
| DEC Arm A: 40 mg Cobimetinib + 400 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 1750 nanograms*hours/milliliter (ng*h/mL) | — |
| DEC Arm A: 40 mg Cobimetinib + 400 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 2170 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 74.9 |
| DEC Arm B: 100 mg Cobimetinib + 200 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 255 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 203 |
| DEC Arm B: 100 mg Cobimetinib + 200 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 3230 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 96.8 |
| DEC Arm B: 100 mg Cobimetinib + 200 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 599 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 133 |
| DEC Arm B: 100 mg Cobimetinib + 200 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 3740 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 139 |
| DEC Arm B: 125 mg Cobimetinib + 200 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 5580 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 54.4 |
| DEC Arm B: 125 mg Cobimetinib + 200 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 956 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 43.5 |
| DEC Arm B: 125 mg Cobimetinib + 200 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 1760 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 62.3 |
| DEC Arm B: 125 mg Cobimetinib + 200 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 8140 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 5.65 |
| DEC Arm B: 125 mg Cobimetinib + 400 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 4400 nanograms*hours/milliliter (ng*h/mL) | — |
| DEC Arm B: 125 mg Cobimetinib + 400 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 1420 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 46.4 |
| DEC Arm B: 125 mg Cobimetinib + 400 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 2230 nanograms*hours/milliliter (ng*h/mL) | — |
| DEC Arm B: 125 mg Cobimetinib + 400 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 2690 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 50.7 |
| DEC Arm B: 150 mg Cobimetinib + 300 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 1260 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 85.2 |
| DEC Arm B: 150 mg Cobimetinib + 300 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 2710 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 60.7 |
| DEC Arm B: 150 mg Cobimetinib + 300 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 4970 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 65.5 |
| DEC Arm B: 150 mg Cobimetinib + 300 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 790 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 78.8 |
| DEC Arm B: 175 mg Cobimetinib + 200 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 8570 nanograms*hours/milliliter (ng*h/mL) | — |
| DEC Arm B: 175 mg Cobimetinib + 200 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 838 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 239 |
| DEC Arm B: 175 mg Cobimetinib + 200 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 13600 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 111 |
| DEC Arm B: 175 mg Cobimetinib + 200 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 668 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 148 |
| DEC Arm B: 150 mg Cobimetinib + 200 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 866 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 58.1 |
| DEC Arm B: 150 mg Cobimetinib + 200 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 3270 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 89.2 |
| DEC Arm B: 150 mg Cobimetinib + 200 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 3980 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 111 |
| DEC Arm B: 150 mg Cobimetinib + 200 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 424 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 67.9 |
| DEC Arm B: 100 mg Cobimetinib + 400 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 4330 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 39.3 |
| DEC Arm B: 100 mg Cobimetinib + 400 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 2030 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 46.4 |
| DEC Arm B: 100 mg Cobimetinib + 400 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 6830 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 38.4 |
| DEC Arm B: 100 mg Cobimetinib + 400 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 3390 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 9.7 |
| Endometrial Carcinoma: 140 mg Cobimetinib + 300 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 11400 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 64.1 |
| Endometrial Carcinoma: 140 mg Cobimetinib + 300 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 1450 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 48.7 |
| Endometrial Carcinoma: 140 mg Cobimetinib + 300 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 1070 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 65.2 |
| Endometrial Carcinoma: 140 mg Cobimetinib + 300 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 8880 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 64.8 |
| Breast Cancer: 140 mg Cobimetinib + 300 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 1270 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 13.3 |
| Breast Cancer: 140 mg Cobimetinib + 300 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 1480 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 10800 |
| Breast Cancer: 140 mg Cobimetinib + 300 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 10800 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 41 |
| Breast Cancer: 140 mg Cobimetinib + 300 mg Ipatasertib | Area Under Concentration-Time Curve From Time Zero to Last Measurable Concentration After Dose [AUC0-Last] of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 1540 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 11.3 |
Secondary
Duration of Objective Response for Participants With Measurable Disease According to RECIST v1.1
Duration of response, defined as the time from first occurrence of a documented objective response until the time of disease progression, as determined by investigator review of tumor assessments using RECIST 1.1, or death from any cause during the study (i.e., within 30 days after the last dose of study treatment).
Time frame: Screening, Days 21-28 of Cycle 2, Day 25 (± 3 days) of Cycle 4 and every 8 weeks thereafter till study completion (Up to 33 months)
Population: This outcome measure was not analyzed as per changes in planned analysis due to very few participants with measurable response.
Secondary
Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15
Time frame: Predose (0 hour), 1, 2, 4, 6 and 24 hours postdose on Day 1 and Day 15 of Cycle 1
Population: Pharmacokinetic analysis population. n represents the number of participants who were evaluable for that particular assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DEC Arm A: 40 mg Cobimetinib + 200 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 79.4 ng/mL | Standard Deviation 119 |
| DEC Arm A: 40 mg Cobimetinib + 200 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 14.1 ng/mL | Standard Deviation 4.54 |
| DEC Arm A: 40 mg Cobimetinib + 200 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 228 ng/mL | Standard Deviation 319 |
| DEC Arm A: 40 mg Cobimetinib + 200 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 6.18 ng/mL | Standard Deviation 4.9 |
| DEC Arm A: 60 mg Cobimetinib + 200 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 11.6 ng/mL | Standard Deviation 1.79 |
| DEC Arm A: 60 mg Cobimetinib + 200 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 35.9 ng/mL | Standard Deviation 10.5 |
| DEC Arm A: 60 mg Cobimetinib + 200 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 105 ng/mL | Standard Deviation 58.3 |
| DEC Arm A: 60 mg Cobimetinib + 200 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 6.07 ng/mL | Standard Deviation 1.99 |
| DEC Arm A: 60 mg Cobimetinib + 300 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 150 ng/mL | — |
| DEC Arm A: 60 mg Cobimetinib + 300 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 251 ng/mL | Standard Deviation 192 |
| DEC Arm A: 60 mg Cobimetinib + 300 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 38.0 ng/mL | Standard Deviation 14.5 |
| DEC Arm A: 60 mg Cobimetinib + 300 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 23.7 ng/mL | — |
| DEC Arm A: 40 mg Cobimetinib + 400 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 71.9 ng/mL | Standard Deviation 44 |
| DEC Arm A: 40 mg Cobimetinib + 400 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 93.8 ng/mL | — |
| DEC Arm A: 40 mg Cobimetinib + 400 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 30.6 ng/mL | — |
| DEC Arm A: 40 mg Cobimetinib + 400 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 25.1 ng/mL | Standard Deviation 11.3 |
| DEC Arm B: 100 mg Cobimetinib + 200 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 4.32 ng/mL | Standard Deviation 2.6 |
| DEC Arm B: 100 mg Cobimetinib + 200 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 123 ng/mL | Standard Deviation 70.2 |
| DEC Arm B: 100 mg Cobimetinib + 200 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 12.8 ng/mL | Standard Deviation 6.85 |
| DEC Arm B: 100 mg Cobimetinib + 200 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 122 ng/mL | Standard Deviation 76.5 |
| DEC Arm B: 125 mg Cobimetinib + 200 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 204 ng/mL | Standard Deviation 172 |
| DEC Arm B: 125 mg Cobimetinib + 200 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 13.4 ng/mL | Standard Deviation 8.29 |
| DEC Arm B: 125 mg Cobimetinib + 200 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 30.6 ng/mL | Standard Deviation 22.2 |
| DEC Arm B: 125 mg Cobimetinib + 200 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 294 ng/mL | Standard Deviation 158 |
| DEC Arm B: 125 mg Cobimetinib + 400 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 127 ng/mL | — |
| DEC Arm B: 125 mg Cobimetinib + 400 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 15.2 ng/mL | Standard Deviation 5.15 |
| DEC Arm B: 125 mg Cobimetinib + 400 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 39.3 ng/mL | — |
| DEC Arm B: 125 mg Cobimetinib + 400 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 72.6 ng/mL | Standard Deviation 30.7 |
| DEC Arm B: 150 mg Cobimetinib + 300 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 21.90 ng/mL | Standard Deviation 45.5 |
| DEC Arm B: 150 mg Cobimetinib + 300 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 145 ng/mL | Standard Deviation 159 |
| DEC Arm B: 150 mg Cobimetinib + 300 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 186 ng/mL | Standard Deviation 116 |
| DEC Arm B: 150 mg Cobimetinib + 300 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 7.05 ng/mL | Standard Deviation 11.6 |
| DEC Arm B: 175 mg Cobimetinib + 200 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 283 ng/mL | — |
| DEC Arm B: 175 mg Cobimetinib + 200 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 18.2 ng/mL | Standard Deviation 16.2 |
| DEC Arm B: 175 mg Cobimetinib + 200 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 1280 ng/mL | Standard Deviation 1120 |
| DEC Arm B: 175 mg Cobimetinib + 200 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 13.0 ng/mL | Standard Deviation 7.66 |
| DEC Arm B: 150 mg Cobimetinib + 200 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 16.9 ng/mL | Standard Deviation 10.9 |
| DEC Arm B: 150 mg Cobimetinib + 200 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 125 ng/mL | Standard Deviation 127 |
| DEC Arm B: 150 mg Cobimetinib + 200 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 204 ng/mL | Standard Deviation 254 |
| DEC Arm B: 150 mg Cobimetinib + 200 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 6.00 ng/mL | Standard Deviation 4.18 |
| DEC Arm B: 100 mg Cobimetinib + 400 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 160 ng/mL | Standard Deviation 17.7 |
| DEC Arm B: 100 mg Cobimetinib + 400 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 30.0 ng/mL | Standard Deviation 5.66 |
| DEC Arm B: 100 mg Cobimetinib + 400 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 280 ng/mL | Standard Deviation 53 |
| DEC Arm B: 100 mg Cobimetinib + 400 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 54.7 ng/mL | Standard Deviation 15.5 |
| Endometrial Carcinoma: 140 mg Cobimetinib + 300 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 386 ng/mL | Standard Deviation 237 |
| Endometrial Carcinoma: 140 mg Cobimetinib + 300 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 18.0 ng/mL | Standard Deviation 10.1 |
| Endometrial Carcinoma: 140 mg Cobimetinib + 300 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 20.7 ng/mL | Standard Deviation 12.1 |
| Endometrial Carcinoma: 140 mg Cobimetinib + 300 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 299 ng/mL | Standard Deviation 172 |
| Breast Cancer: 140 mg Cobimetinib + 300 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 14.5 ng/mL | Standard Deviation 8.68 |
| Breast Cancer: 140 mg Cobimetinib + 300 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 227 ng/mL | Standard Deviation 316 |
| Breast Cancer: 140 mg Cobimetinib + 300 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 268 ng/mL | Standard Deviation 146 |
| Breast Cancer: 140 mg Cobimetinib + 300 mg Ipatasertib | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 15.4 ng/mL | Standard Deviation 6.38 |
Secondary
Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15
Time frame: Predose (0 hour), 1, 2, 4, 6 and 24 hours postdose on Day 1 and Day 15 of Cycle 1
Population: Pharmacokinetic analysis population. n represents the number of participants who were evaluable for that particular assessment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| DEC Arm A: 40 mg Cobimetinib + 200 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 134 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 333 |
| DEC Arm A: 40 mg Cobimetinib + 200 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 94.5 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 55 |
| DEC Arm A: 40 mg Cobimetinib + 200 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 222 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 182 |
| DEC Arm A: 40 mg Cobimetinib + 200 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 137 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 244 |
| DEC Arm A: 60 mg Cobimetinib + 200 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 130 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 47.1 |
| DEC Arm A: 60 mg Cobimetinib + 200 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 78.6 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 73.2 |
| DEC Arm A: 60 mg Cobimetinib + 200 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 215 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 61.4 |
| DEC Arm A: 60 mg Cobimetinib + 200 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 97.1 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 92.2 |
| DEC Arm A: 60 mg Cobimetinib + 300 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 312 nanograms per milliliter (ng/mL) | — |
| DEC Arm A: 60 mg Cobimetinib + 300 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 407 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 72.6 |
| DEC Arm A: 60 mg Cobimetinib + 300 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 386 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 58.4 |
| DEC Arm A: 60 mg Cobimetinib + 300 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 300 nanograms per milliliter (ng/mL) | — |
| DEC Arm A: 40 mg Cobimetinib + 400 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 109 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 85.4 |
| DEC Arm A: 40 mg Cobimetinib + 400 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 121 nanograms per milliliter (ng/mL) | — |
| DEC Arm A: 40 mg Cobimetinib + 400 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 137 nanograms per milliliter (ng/mL) | — |
| DEC Arm A: 40 mg Cobimetinib + 400 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 336 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 118 |
| DEC Arm B: 100 mg Cobimetinib + 200 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 42.9 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 560 |
| DEC Arm B: 100 mg Cobimetinib + 200 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 217 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 135 |
| DEC Arm B: 100 mg Cobimetinib + 200 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 86.9 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 237 |
| DEC Arm B: 100 mg Cobimetinib + 200 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 259 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 192 |
| DEC Arm B: 125 mg Cobimetinib + 200 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 405 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 45.9 |
| DEC Arm B: 125 mg Cobimetinib + 200 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 156 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 32.8 |
| DEC Arm B: 125 mg Cobimetinib + 200 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 165 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 33.9 |
| DEC Arm B: 125 mg Cobimetinib + 200 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 511 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 14.6 |
| DEC Arm B: 125 mg Cobimetinib + 400 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 376 nanograms per milliliter (ng/mL) | — |
| DEC Arm B: 125 mg Cobimetinib + 400 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 329 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 104 |
| DEC Arm B: 125 mg Cobimetinib + 400 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 441 nanograms per milliliter (ng/mL) | — |
| DEC Arm B: 125 mg Cobimetinib + 400 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 192 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 50.3 |
| DEC Arm B: 150 mg Cobimetinib + 300 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 170 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 64.4 |
| DEC Arm B: 150 mg Cobimetinib + 300 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 220 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 64.9 |
| DEC Arm B: 150 mg Cobimetinib + 300 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 320 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 64.5 |
| DEC Arm B: 150 mg Cobimetinib + 300 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 141 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 34.3 |
| DEC Arm B: 175 mg Cobimetinib + 200 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 481 nanograms per milliliter (ng/mL) | — |
| DEC Arm B: 175 mg Cobimetinib + 200 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 99.9 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 254 |
| DEC Arm B: 175 mg Cobimetinib + 200 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 1040 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 151 |
| DEC Arm B: 175 mg Cobimetinib + 200 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 72.9 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 200 |
| DEC Arm B: 150 mg Cobimetinib + 200 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 114 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 53.9 |
| DEC Arm B: 150 mg Cobimetinib + 200 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 262 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 59.9 |
| DEC Arm B: 150 mg Cobimetinib + 200 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 253 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 103 |
| DEC Arm B: 150 mg Cobimetinib + 200 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 95.8 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 57.1 |
| DEC Arm B: 100 mg Cobimetinib + 400 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 249 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 46 |
| DEC Arm B: 100 mg Cobimetinib + 400 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 262 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 122 |
| DEC Arm B: 100 mg Cobimetinib + 400 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 420 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 41.4 |
| DEC Arm B: 100 mg Cobimetinib + 400 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 450 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 16.9 |
| Endometrial Carcinoma: 140 mg Cobimetinib + 300 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 799 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 55.8 |
| Endometrial Carcinoma: 140 mg Cobimetinib + 300 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 268 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 48.3 |
| Endometrial Carcinoma: 140 mg Cobimetinib + 300 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 149 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 113 |
| Endometrial Carcinoma: 140 mg Cobimetinib + 300 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 704 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 75.2 |
| Breast Cancer: 140 mg Cobimetinib + 300 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 156 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 12.7 |
| Breast Cancer: 140 mg Cobimetinib + 300 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 84.2 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 7940 |
| Breast Cancer: 140 mg Cobimetinib + 300 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 840 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 56.6 |
| Breast Cancer: 140 mg Cobimetinib + 300 mg Ipatasertib | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 374 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 48.2 |
Secondary
Number of Participants With Objective Response of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
RECIST v1.1 (for measurable disease), CR: disappearance of all target lesions, reduction in short axis \<10 millimeters in pathological lymph nodes (target and non-target lesions); PR: at least a 30 percent (%) decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. Responses were confirmed by repeat assessments ≥4 weeks after initial documentation.
Time frame: Screening, Days 21-28 of Cycle 2, Day 25 (± 3 days) of Cycle 4 and every 8 weeks thereafter till study completion (Up to 33 months)
Population: Safety analysis population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DEC Arm A: 40 mg Cobimetinib + 200 mg Ipatasertib | Number of Participants With Objective Response of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | 0 participants |
| DEC Arm A: 60 mg Cobimetinib + 200 mg Ipatasertib | Number of Participants With Objective Response of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | 0 participants |
| DEC Arm A: 60 mg Cobimetinib + 300 mg Ipatasertib | Number of Participants With Objective Response of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | 0 participants |
| DEC Arm A: 40 mg Cobimetinib + 400 mg Ipatasertib | Number of Participants With Objective Response of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | 1 participants |
| DEC Arm B: 100 mg Cobimetinib + 200 mg Ipatasertib | Number of Participants With Objective Response of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | 1 participants |
| DEC Arm B: 125 mg Cobimetinib + 200 mg Ipatasertib | Number of Participants With Objective Response of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | 0 participants |
| DEC Arm B: 125 mg Cobimetinib + 400 mg Ipatasertib | Number of Participants With Objective Response of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | 0 participants |
| DEC Arm B: 150 mg Cobimetinib + 300 mg Ipatasertib | Number of Participants With Objective Response of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | 0 participants |
| DEC Arm B: 175 mg Cobimetinib + 200 mg Ipatasertib | Number of Participants With Objective Response of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | 1 participants |
| DEC Arm B: 150 mg Cobimetinib + 200 mg Ipatasertib | Number of Participants With Objective Response of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | 0 participants |
| DEC Arm B: 100 mg Cobimetinib + 400 mg Ipatasertib | Number of Participants With Objective Response of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | 0 participants |
| Endometrial Carcinoma: 140 mg Cobimetinib + 300 mg Ipatasertib | Number of Participants With Objective Response of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | 0 participants |
| Breast Cancer: 140 mg Cobimetinib + 300 mg Ipatasertib | Number of Participants With Objective Response of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | 0 participants |
Secondary
Progression-Free Survival (PFS) Time for Participants With Measurable Disease According to RECIST v1.1
PFS is defined as the time from study treatment initiation to the first occurrence of disease progression, as determined by investigator review of tumor assessments using RECIST 1.1, or death from any cause during the study (i.e., within 30 days after the last dose of study treatment).
Time frame: Screening, Days 21-28 of Cycle 2, Day 25 (± 3 days) of Cycle 4 and every 8 weeks thereafter till study completion (Up to 33 months)
Population: This outcome measure was not analyzed as per changes in planned analysis due to very few participants with measurable response.
Secondary
Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15
Time frame: Predose (0 hour), 1, 2, 4, 6 and 24 hours postdose on Day 1 and Day 15 of Cycle 1
Population: Pharmacokinetic analysis population. n represents the number of participants who were evaluable for that particular assessment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| DEC Arm A: 40 mg Cobimetinib + 200 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 2.25 hours |
| DEC Arm A: 40 mg Cobimetinib + 200 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 2.00 hours |
| DEC Arm A: 40 mg Cobimetinib + 200 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 2.03 hours |
| DEC Arm A: 40 mg Cobimetinib + 200 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 1.03 hours |
| DEC Arm A: 60 mg Cobimetinib + 200 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 1.02 hours |
| DEC Arm A: 60 mg Cobimetinib + 200 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 3.92 hours |
| DEC Arm A: 60 mg Cobimetinib + 200 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 1.03 hours |
| DEC Arm A: 60 mg Cobimetinib + 200 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 3.97 hours |
| DEC Arm A: 60 mg Cobimetinib + 300 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 2.05 hours |
| DEC Arm A: 60 mg Cobimetinib + 300 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 1.00 hours |
| DEC Arm A: 60 mg Cobimetinib + 300 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 3.01 hours |
| DEC Arm A: 60 mg Cobimetinib + 300 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 1.04 hours |
| DEC Arm A: 40 mg Cobimetinib + 400 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 3.83 hours |
| DEC Arm A: 40 mg Cobimetinib + 400 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 6.05 hours |
| DEC Arm A: 40 mg Cobimetinib + 400 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 1.04 hours |
| DEC Arm A: 40 mg Cobimetinib + 400 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 6.05 hours |
| DEC Arm B: 100 mg Cobimetinib + 200 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 3.04 hours |
| DEC Arm B: 100 mg Cobimetinib + 200 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 1.00 hours |
| DEC Arm B: 100 mg Cobimetinib + 200 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 1.04 hours |
| DEC Arm B: 100 mg Cobimetinib + 200 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 4.78 hours |
| DEC Arm B: 125 mg Cobimetinib + 200 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 3.04 hours |
| DEC Arm B: 125 mg Cobimetinib + 200 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 3.03 hours |
| DEC Arm B: 125 mg Cobimetinib + 200 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 4.03 hours |
| DEC Arm B: 125 mg Cobimetinib + 200 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 1.00 hours |
| DEC Arm B: 125 mg Cobimetinib + 400 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 1.88 hours |
| DEC Arm B: 125 mg Cobimetinib + 400 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 1.00 hours |
| DEC Arm B: 125 mg Cobimetinib + 400 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 1.00 hours |
| DEC Arm B: 125 mg Cobimetinib + 400 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 4.05 hours |
| DEC Arm B: 150 mg Cobimetinib + 300 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 1.19 hours |
| DEC Arm B: 150 mg Cobimetinib + 300 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 4.00 hours |
| DEC Arm B: 150 mg Cobimetinib + 300 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 4.06 hours |
| DEC Arm B: 150 mg Cobimetinib + 300 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 2.00 hours |
| DEC Arm B: 175 mg Cobimetinib + 200 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 3.17 hours |
| DEC Arm B: 175 mg Cobimetinib + 200 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 1.57 hours |
| DEC Arm B: 175 mg Cobimetinib + 200 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 24.0 hours |
| DEC Arm B: 175 mg Cobimetinib + 200 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 5.92 hours |
| DEC Arm B: 150 mg Cobimetinib + 200 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 3.91 hours |
| DEC Arm B: 150 mg Cobimetinib + 200 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 4.00 hours |
| DEC Arm B: 150 mg Cobimetinib + 200 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 1.00 hours |
| DEC Arm B: 150 mg Cobimetinib + 200 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 1.08 hours |
| DEC Arm B: 100 mg Cobimetinib + 400 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 0.98 hours |
| DEC Arm B: 100 mg Cobimetinib + 400 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 5.92 hours |
| DEC Arm B: 100 mg Cobimetinib + 400 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 1.52 hours |
| DEC Arm B: 100 mg Cobimetinib + 400 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 13.1 hours |
| Endometrial Carcinoma: 140 mg Cobimetinib + 300 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 1.08 hours |
| Endometrial Carcinoma: 140 mg Cobimetinib + 300 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 1.47 hours |
| Endometrial Carcinoma: 140 mg Cobimetinib + 300 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 3.08 hours |
| Endometrial Carcinoma: 140 mg Cobimetinib + 300 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 2.00 hours |
| Breast Cancer: 140 mg Cobimetinib + 300 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 2.08 hours |
| Breast Cancer: 140 mg Cobimetinib + 300 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Cobimetinib Day 15 (n=3,6,2,1,4,3,1,6,1,5,2,7,2) | 1.96 hours |
| Breast Cancer: 140 mg Cobimetinib + 300 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 15 (n=3,6,2,1,4,3,1,6,2,5,2,7,2) | 0.97 hours |
| Breast Cancer: 140 mg Cobimetinib + 300 mg Ipatasertib | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Ipatasertib Day 1 (n=3,7,1,4,4,4,3,5,2,6,2,14,5) | 1.00 hours |