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| ID | Type | Description | Link |
|---|---|---|---|
| 2012-003934-18 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose escalation stage 1 (Arm A): Cobimetinib and Ipatasertib | Experimental | Participants will receive cobimetinib (GDC-0973) capsules (at a starting dose of 40 mg) and ipatasertib (GDC-0068) capsules (at a starting dose of 200 mg) from Days 1 to 21 and then 7 days off study drugs from Days 22 to 28 in continuous 28-day cycles. Doses will be increased to identify maximum tolerated dose (MTD) or potential recommended Phase 2 dose (RP2D). Treatment will continue until disease progression, unacceptable toxicity, or any other discontinuation criterion meets. |
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| Dose escalation stage 1 (Arm B): Cobimetinib and Ipatasertib | Experimental | Participants will receive cobimetinib (GDC-0973) capsules (at a starting dose of 100 mg) on Days 1, 4, 8, 11, 15, and 18 and ipatasertib (GDC-0068) capsules (at a starting dose of 200 mg) from Days 1 to 21 and then 7 days off study drugs from Days 22 to 28 in continuous 28-day cycles. Doses will be increased to identify MTD or potential RP2D. Treatment will continue until disease progression, unacceptable toxicity, or any other discontinuation criterion meets. |
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| Stage 2 (Indication specific dose expansion cohort) | Experimental | Participants will receive cobimetinib (GDC-0973) capsules on Days 1, 4, 8, 11, 15, and 18 and ipatasertib (GDC-0068) capsules from Days 1 to 21 and then 7 days off study drugs from Days 22 to 28 in continuous 28-day cycles, at doses identified as MTD/potential RP2D from Stage 1. Treatment will continue until disease progression, unacceptable toxicity, or any other discontinuation criterion meets. This indication specific cohort will include participants with phosphatase and tensin homolog (PTEN)-loss triple-negative breast cancer and PTEN-loss endometrial carcinoma. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ipatasertib | Drug | multiple doses |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Cycle 1 (28 Days) |
| 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. | Cycle 1 (28 Days) |
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | |
| Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Genentech, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Boston | Massachusetts | 02215 | United States | |||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32737717 | Derived | Shapiro GI, LoRusso P, Cho DC, Musib L, Yan Y, Wongchenko M, Chang I, Patel P, Chan IT, Sanabria-Bohorquez S, Meng RD, Bendell JC. A phase Ib open-label dose escalation study of the safety, pharmacokinetics, and pharmacodynamics of cobimetinib (GDC-0973) and ipatasertib (GDC-0068) in patients with locally advanced or metastatic solid tumors. Invest New Drugs. 2021 Feb;39(1):163-174. doi: 10.1007/s10637-020-00975-6. Epub 2020 Jul 31. |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | DEC Arm A: 40 mg Cobimetinib + 200 mg Ipatasertib | Participants received oral 40 milligrams (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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Stage 1 |
|
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| Cobimetinib | Drug | multiple doses |
|
|
| Cycle 1 (28 Days) |
| 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. | 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) |
| 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 |
| 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. | 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 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). | 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) |
| 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). | 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) |
| Detroit |
| Michigan |
| 48201 |
| United States |
| Nashville | Tennessee | 37203 | United States |
| Barcelona | Barcelona | 08035 | Spain |
| Valencia | Valencia | 46010 | Spain |
| FG001 |
| 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. |
| FG002 | 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. |
| FG003 | 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. |
| FG004 | 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. |
| FG005 | 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. |
| FG006 | 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. |
| FG007 | 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. |
| FG008 | 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. |
| FG009 | 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. |
| FG010 | 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. |
| FG011 | 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. |
| FG012 | 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. |
| COMPLETED |
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| NOT COMPLETED |
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| Stage 2 |
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|
All enrolled participants.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | 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. |
| BG002 | 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. |
| BG003 | 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. |
| BG004 | 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. |
| BG005 | 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. |
| BG006 | 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. |
| BG007 | 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. |
| BG008 | 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. |
| BG009 | 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. |
| BG010 | 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. |
| BG011 | 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. |
| BG012 | 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. |
| BG013 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||
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| 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. | 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. | Posted | Number | participants | Cycle 1 (28 Days) |
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| 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. | Data for this outcome measure was not analyzed as no participant experienced DLT. | Posted | Cycle 1 (28 Days) |
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| 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. | Safety analysis population participants from dose escalation cohorts. | Posted | Number | milligrams | Cycle 1 (28 Days) |
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| 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. | Safety analysis population. | Posted | Number | participants | 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) |
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| 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 | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms*hours/milliliter (ng*h/mL) | Predose (0 hour), 1, 2, 4, 6 and 24 hours postdose on Day 1 and Day 15 of Cycle 1 |
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| Secondary | Maximum Plasma Concentration (Cmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Pharmacokinetic analysis population. "n" represents the number of participants who were evaluable for that particular assessment. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms per milliliter (ng/mL) | Predose (0 hour), 1, 2, 4, 6 and 24 hours postdose on Day 1 and Day 15 of Cycle 1 |
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| Secondary | Time Taken to Reach Cmax (Tmax) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Pharmacokinetic analysis population. "n" represents the number of participants who were evaluable for that particular assessment. | Posted | Median | Full Range | hours | Predose (0 hour), 1, 2, 4, 6 and 24 hours postdose on Day 1 and Day 15 of Cycle 1 |
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| Secondary | Last Measurable Concentration (Clast) of Ipatasertib and Cobimetinib on Day 1 and Day 15 | Pharmacokinetic analysis population. "n" represents the number of participants who were evaluable for that particular assessment. | Posted | Mean | Standard Deviation | ng/mL | Predose (0 hour), 1, 2, 4, 6 and 24 hours postdose on Day 1 and Day 15 of Cycle 1 |
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| 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. | Safety analysis population. | Posted | Number | participants | 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) |
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| 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). | This outcome measure was not analyzed as per changes in planned analysis due to very few participants with measurable response. | Posted | 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) |
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| 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). | This outcome measure was not analyzed as per changes in planned analysis due to very few participants with measurable response. | Posted | 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) |
|
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)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. | 1 | 3 | 3 | 3 | ||
| EG001 | 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. | 2 | 7 | 7 | 7 | ||
| EG002 | 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. | 0 | 3 | 3 | 3 | ||
| EG003 | 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. | 2 | 4 | 4 | 4 | ||
| EG004 | 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. | 1 | 4 | 4 | 4 | ||
| EG005 | 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. | 3 | 4 | 4 | 4 | ||
| EG006 | 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. | 1 | 3 | 3 | 3 | ||
| EG007 | 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. | 1 | 7 | 7 | 7 | ||
| EG008 | 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. | 0 | 3 | 3 | 3 | ||
| EG009 | 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. | 2 | 6 | 6 | 6 | ||
| EG010 | 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. | 2 | 3 | 3 | 3 | ||
| EG011 | 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. | 10 | 14 | 14 | 14 | ||
| EG012 | 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. | 2 | 5 | 5 | 5 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial Fibrillation | Cardiac disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Bradycardia | Cardiac disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Abdominal Pain | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Enterocolitis | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Gastrointestinal Haemorrhage | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Intestinal Obstruction | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Large Intestinal Obstruction | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Small Intestinal Obstruction | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Disease Progression | General disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Pain | General disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Bile Duct Obstruction | Hepatobiliary disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Clostridium Difficile Colitis | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Pyelonephritis | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Hip Fracture | Injury, poisoning and procedural complications | MedDRA (17.1) | Non-systematic Assessment |
| |
| Toxicity to Various Agents | Injury, poisoning and procedural complications | MedDRA (17.1) | Non-systematic Assessment |
| |
| Liver Function Test Abnormal | Investigations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Back Pain | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Malignant Neoplasm Progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (17.1) | Non-systematic Assessment |
| |
| Presyncope | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Mental Status Changes | Psychiatric disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Renal Failure | Renal and urinary disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Renal Failure Acute | Renal and urinary disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Acute Respiratory Failure | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Pneumonia Aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Pulmonary Embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Respiratory Distress | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Respiratory Failure | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Haematoma | Vascular disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA (17.1) | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Anaemia Vitamin B12 Deficiency | Blood and lymphatic system disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Hypercoagulation | Blood and lymphatic system disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Leukocytosis | Blood and lymphatic system disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Atrial Fibrillation | Cardiac disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Atrial Flutter | Cardiac disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Bradycardia | Cardiac disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Sinus Bradycardia | Cardiac disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Sinus Tachycardia | Cardiac disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Supraventricular Tachycardia | Cardiac disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Eye Discharge | Eye disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Eye Disorder | Eye disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Eye Pain | Eye disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Lacrimation Increased | Eye disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Ocular Hyperaemia | Eye disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Periorbital Oedema | Eye disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Photopsia | Eye disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Vision Blurred | Eye disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Visual Acuity Reduced Transiently | Eye disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Visual Impairment | Eye disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Vitreous Floaters | Eye disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Abdominal Discomfort | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Abdominal Distension | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Abdominal Pain | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Abdominal Pain Lower | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Abdominal Pain Upper | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Anal Haemorrhage | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Aphthous Stomatitis | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Chapped Lips | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Dry Mouth | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Eructation | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Gastrooesophageal Reflux Disease | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Haematochezia | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Ileus Paralytic | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Lip Dry | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Lip Oedema | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Obstruction Gastric | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Oesophageal Pain | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Oral Pain | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Oral Pruritus | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Pancreatitis | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Paraesthesia Oral | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Peptic Ulcer | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Proctalgia | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Retching | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Tongue Oedema | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Catheter Site Pain | General disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Chest Pain | General disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Chills | General disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Early Satiety | General disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Face Oedema | General disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Gait Disturbance | General disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Malaise | General disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Medical Device Pain | General disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Non-cardiac Chest Pain | General disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Oedema Peripheral | General disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Pain | General disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Peripheral Swelling | General disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Systemic Inflammatory Response Syndrome | General disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Contrast Media Allergy | Immune system disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Hypersensitivity | Immune system disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Acute Sinusitis | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Bacteraemia | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Candida Infection | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Clostridium Difficile Colitis | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Cystitis | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Hordeolum | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Infected Skin Ulcer | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Localised Infection | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Mucosal Infection | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Oral Candidiasis | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Paronychia | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Upper Respiratory Tract Infection | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Urinary Tract Infection | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Vaginal Infection | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Viral Infection | Infections and infestations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Animal Bite | Injury, poisoning and procedural complications | MedDRA (17.1) | Non-systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA (17.1) | Non-systematic Assessment |
| |
| Laceration | Injury, poisoning and procedural complications | MedDRA (17.1) | Non-systematic Assessment |
| |
| Alanine Aminotransferase Increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Amylase Increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Aspartate Aminotransferase Increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Blood Alkaline Phosphatase | Investigations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Blood Alkaline Phosphatase Increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Blood Calcium Decreased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Blood Chloride Decreased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Blood Cholesterol Increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Blood Creatine Phosphokinase Increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Blood Creatinine Decreased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Blood Creatinine Increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Blood Glucose Increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Blood Insulin Increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Blood Lactate Dehydrogenase Increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Blood Sodium Decreased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Blood Urea Decreased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Blood Urea Increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Blood Uric Acid Increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Carbohydrate Antigen 15-3 Increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Carbon Dioxide Decreased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Cardiac Murmur | Investigations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Electrocardiogram QT Prolonged | Investigations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Heart Rate Increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
| |
| High Density Lipoprotein Decreased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Insulin C-peptide Increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Lipase Increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Lymphocyte Count Decreased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Monocyte Count Increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Neutrophil Count Increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Oxygen Saturation Decreased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Protein Total Increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Urine Output Decreased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Weight Decreased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
| |
| White Blood Cell Count Decreased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
| |
| White Blood Cell Count Increased | Investigations | MedDRA (17.1) | Non-systematic Assessment |
| |
| Decreased Appetite | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Gout | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Hypercholesterolaemia | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Hypertriglyceridaemia | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Malnutrition | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Salt Craving | Metabolism and nutrition disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Back Pain | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Bone Pain | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Flank Pain | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Groin Pain | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Muscle Spasms | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Muscular Weakness | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Musculoskeletal Chest Pain | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Musculoskeletal Pain | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Neck Pain | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Pain in Extremity | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Tendonitis | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Depressed Level of Consciousness | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Disturbance in Attention | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Hypoaesthesia | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Lethargy | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Memory Impairment | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Migraine with Aura | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Monoplegia | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Polyneuropathy | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Sciatica | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Visual Field Defect | Nervous system disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Confusional State | Psychiatric disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Hallucination | Psychiatric disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Hallucination, Visual | Psychiatric disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Mental Status Changes | Psychiatric disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Bladder Spasm | Renal and urinary disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Chromaturia | Renal and urinary disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Hydronephrosis | Renal and urinary disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Incontinence | Renal and urinary disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Micturition Urgency | Renal and urinary disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Oliguria | Renal and urinary disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Pollakiuria | Renal and urinary disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Renal Failure | Renal and urinary disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Renal Failure Acute | Renal and urinary disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Oedema Genital | Reproductive system and breast disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Pelvic Pain | Reproductive system and breast disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Pruritus Genital | Reproductive system and breast disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Vaginal Discharge | Reproductive system and breast disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Vaginal Haemorrhage | Reproductive system and breast disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Atelectasis | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Dyspnoea Exertional | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Nasal Congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Nasal Discomfort | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Oropharyngeal Pain | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Painful Respiration | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Pleural Effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Productive Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Pulmonary Congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Pulmonary Embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Sinus Congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Throat Irritation | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Upper-airway Cough Syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Decubitus Ulcer | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Dermatitis Acneiform | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Dry Skin | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Nail Discolouration | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Onychoclasis | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Rash Erythematous | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Rash Generalised | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Rash Macular | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Rash Maculo-papular | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Rash Pruritic | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Skin Disorder | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Sinus Operation | Surgical and medical procedures | MedDRA (17.1) | Non-systematic Assessment |
| |
| Deep Vein Thrombosis | Vascular disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Embolism | Vascular disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Flushing | Vascular disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Hot Flush | Vascular disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Lymphoedema | Vascular disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Subclavian Vein Thrombosis | Vascular disorders | MedDRA (17.1) | Non-systematic Assessment |
| |
| Haemorrhoids | Gastrointestinal disorders | MedDRA (17.1) | Non-systematic Assessment |
|
As per changes in the planned analysis, PFS and duration of response outcome measures were not analyzed as only few participants experienced a measurable response.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Communications | Hoffmann-LaRoche | 800-821-8590 | genentech@druginfo.com |
| ID | Term |
|---|---|
| D009369 | Neoplasms |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| C583616 | ipatasertib |
| C574276 | cobimetinib |
Not provided
Not provided
Not provided
| Progression of Disease |
|
| Male |
|
| OG005 | 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. |
| OG006 | 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. |
| OG007 | 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. |
| OG008 | 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. |
| OG009 | 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. |
| OG010 | 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. |
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. |
| OG002 | 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. |
| OG003 | 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. |
| OG004 | 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. |
| OG005 | 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. |
| OG006 | 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. |
| OG007 | 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. |
| OG008 | 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. |
| OG009 | 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. |
| OG010 | 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. |
|
|
|
| Units | Counts |
|---|
| Participants |
|
|
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. |
| OG003 | 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. |
| OG004 | 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. |
| OG005 | 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. |
| OG006 | 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. |
| OG007 | 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. |
| OG008 | 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. |
| OG009 | 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. |
| OG010 | 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. |
| OG011 | 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. |
| OG012 | 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. |
|
|
| OG003 | 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. |
| OG004 | 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. |
| OG005 | 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. |
| OG006 | 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. |
| OG007 | 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. |
| OG008 | 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. |
| OG009 | 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. |
| OG010 | 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. |
| OG011 | 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. |
| OG012 | 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. |
|
|
| OG003 | 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. |
| OG004 | 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. |
| OG005 | 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. |
| OG006 | 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. |
| OG007 | 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. |
| OG008 | 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. |
| OG009 | 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. |
| OG010 | 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. |
| OG011 | 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. |
| OG012 | 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. |
|
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| OG003 | 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. |
| OG004 | 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. |
| OG005 | 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. |
| OG006 | 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. |
| OG007 | 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. |
| OG008 | 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. |
| OG009 | 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. |
| OG010 | 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. |
| OG011 | 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. |
| OG012 | 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. |
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| OG002 | 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. |
| OG003 | 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. |
| OG004 | 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. |
| OG005 | 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. |
| OG006 | 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. |
| OG007 | 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. |
| OG008 | 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. |
| OG009 | 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. |
| OG010 | 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. |
| OG011 | 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. |
| OG012 | 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. |
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| OG002 |
| 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. |
| OG003 | 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. |
| OG004 | 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. |
| OG005 | 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. |
| OG006 | 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. |
| OG007 | 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. |
| OG008 | 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. |
| OG009 | 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. |
| OG010 | 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. |
| OG011 | 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. |
| OG012 | 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. |
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| 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. |
| OG003 | 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. |
| OG004 | 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. |
| OG005 | 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. |
| OG006 | 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. |
| OG007 | 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. |
| OG008 | 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. |
| OG009 | 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. |
| OG010 | 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. |
| OG011 | 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. |
| OG012 | 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. |
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