Solid Tumors
Conditions
Keywords
GDC0941, GDC0973, MEK, MEK Inhibitor, PI3K, PI3K Inhibitor, PI3 Kinase, PI3 Kinase Inhibitor
Brief summary
This is an open-label, multicenter, Phase Ib dose-escalation study designed to assess the safety, tolerability and pharmacokinetics of oral dosing of cobimetinib and pictilisib administered in combination in patients with locally advanced or metastatic solid tumors.
Interventions
DRUGCobimetinib
Repeated oral dosing.
DRUGPictilisib
Repeated oral dosing.
Sponsors
Genentech, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically documented, locally advanced or metastatic solid tumors for which standard therapy either does not exist or has proven ineffective or intolerable * Evaluable disease or disease measurable per Response Evaluation Criteria in Solid Tumors (RECIST) * Life expectancy greater than or equal to (\>=) 12 weeks * Adequate hematologic and end organ function * Agreement to use an effective form of contraception for the duration of the study
Exclusion criteria
* History of prior significant toxicity from another mitogen-activated protein kinase (MEK) pathway inhibitor requiring discontinuation of treatment * History of prior significant toxicity from another phosphoinositide 3-kinase (PI3K) pathway inhibitor requiring discontinuation of treatment * Allergy or hypersensitivity to components of the cobimetinib or pictilisib formulations * Palliative radiotherapy within 2 weeks prior to first dose of study drug treatment in Cycle 1 * Experimental therapy within 4 weeks prior to first dose of study drug treatment in Cycle 1 * Major surgical procedure or significant traumatic injury within 4 weeks prior to first dose of study drug treatment in Cycle 1, or anticipation of the need for major surgery during the course of study treatment * Prior anti-cancer therapy within 28 days before the first dose of study drug treatment in Cycle 1 * History of diabetes requiring daily medication, or history of Grade \>= 3 fasting hyperglycemia * Current severe, uncontrolled systemic disease * History of clinically significant cardiac or pulmonary dysfunction * History of malabsorption or other condition that would interfere with enteral absorption * Clinically significant history of liver disease (including cirrhosis), current alcohol abuse, or current known active infection with human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus * Any condition requiring anticoagulants, such as warfarin, heparin, or thrombolytics * Active autoimmune disease * Uncontrolled ascites requiring weekly large volume paracentesis for 3 consecutive weeks prior to enrollment * Pregnancy, lactation, or breastfeeding * Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms * No other history of or ongoing malignancy that would potentially interfere with the interpretation of the pharmacodynamic or efficacy assays
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-Time Curve From Time 0 to 24 Hours Post-Dose (AUC0-24) of Cobimetinib on Day 3 - Stage 1, Cohorts 1-3 | 0-4 hours Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Day 3, Day 4 | — |
| Tmax of Pictilisib on Day 1 - Stage 1, Cohorts 1-3 | 0-4 hours pre-pictilisib (Pr-P) dose, 0.5, 2, 4, 6 hours post-pictilisib (Po-P) dose on Day 1, Day 2, 0-4 hours Pr-C dose on Day 3 | — |
| Cmax of Pictilisib on Day 1 - Stage 1, Cohorts 1-3 | 0-4 hours Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Day 1, Day 2, 0-4 hours Pr-C dose on Day 3 | — |
| Time of Maximum Concentration (Tmax) of Cobimetinib on Day 3 - Stage 1, Cohorts 1-3 | 0-4 hours pre-cobimetinib (Pr-C) dose, 0.5, 2, 4, 6 hours post-cobimetinib (Po-C) dose on Day 3, Day 4 | — |
| Number of Participants With Dose-Limiting Toxicities (DLTs) During Dose Escalation Stages 1, 1A and 1B | Cohorts 1-3: Day 1 to Day 35, All other cohorts: Day 1 to Day 28 | DLT was defined as 1 of the following toxicities considered treatment related by Investigator: Grade ≥3 non-hematologic, non-hepatic organ toxicity, excluding the following: Grade 3 nausea, vomiting, or diarrhea that resolved to Grade ≤1 within 7 days, Grade 3 rash or Grade ≥3 fatigue that resolved to Grade ≤2 within 7 days, Grade ≥3 hyperglycemia or lipid profile results that occurred during non-fasting conditions, Grade 3 or 4 elevation of serum creatine phosphokinase levels or Grade 3 non clinically significant (as assessed by Investigator) laboratory abnormality that was asymptomatic; Grade ≥3 febrile neutropenia; Grade ≥4 neutropenia (absolute neutrophil count \<500/microliter) lasting \>5 days; Grade ≥4 thrombocytopenia lasting \>48 hours; Grade ≥4 anemia; Grade ≥3 total bilirubin, hepatic transaminase, alkaline phosphatase, lasting \>72 hours; Grade ≥2 diffusion capacity of the lung for carbon monoxide concomitant with an absolute decrease of ≥20 percentage points from baseline. |
| Maximum Tolerated Combination Doses of Cobimetinib and Pictilisib During Dose-Escalation Stages 1, 1A and 1B | Cohorts 1-3: Day 1 to Day 35, All other cohorts: Day 1 to Day 28 | MTD was determined (by Investigator) based on the DLTs, as well as adverse events (AEs) in dose-escalation Stages 1, 1A, and 1B that did not meet protocol-defined DLT criteria but indicated intolerability of a given dose combination. Separate combination MTDs were determined for each dose-escalation stage. DLT was defined as 1 of the following toxicities considered treatment related by Investigator: Grade ≥3 non-hematologic, non-hepatic organ toxicity; Grade ≥3 febrile neutropenia; Grade ≥4 neutropenia (absolute neutrophil count \<500/microliter) lasting \>5 days; Grade ≥4 thrombocytopenia lasting \>48 hours; Grade ≥4 anemia; Grade ≥3 total bilirubin, hepatic transaminase, alkaline phosphatase, lasting \>72 hours; Grade ≥2 diffusion capacity of the lung for carbon monoxide concomitant with an absolute decrease of ≥20 percentage points from baseline. |
| Maximum Plasma Concentration (Cmax) of Cobimetinib on Day 3 - Stage 1, Cohorts 1-3 | 0-4 hours Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Day 3, Day 4 | — |
| AUC0-24 of Pictilisib on Day 1 - Stage 1, Cohorts 1-3 | 0-4 hours Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Day 1, Day 2, 0-4 hours Pr-C dose on Day 3 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | Cohorts 1-3: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 28, Cycle 1 Day 29, Cycle 2 Days 1, 15, 21; Cohorts 4-6A: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22, Cycle 2 Days 1, 15, 21 | — |
| Tmax of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | Cohorts 1-3: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 28, Cycle 1 Day 29, Cycle 2 Days 1, 15, 21; Cohorts 4-6A: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22, Cycle 2 Days 1, 15, 21 | — |
| AUC0-24 of Pictilisib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | Cohorts 1-3: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 8, Cycle 1 Day 9; Cohorts 4-6A: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Day 2 | — |
| Accumulation Ratio of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Days 1 and 18, Cycle 1 Days 2, 19 | Accumulation ratio was calculated as: AUC0-24 at Cycle 1 Day 18 divided by AUC0-24 at Cycle 1 Day 1. |
| AUC0-24 of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | Cohorts 1-3: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 28, Cycle 1 Day 29; Cohorts 4-6A: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22 | — |
| Terminal Half-life (t1/2) of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | Cohorts 1-3: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 28, Cycle 1 Day 29, Cycle 2 Days 1, 15, 21; Cohorts 4-6A: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22, Cycle 2 Days 1, 15, 21 | Half-life is the time measured for the plasma concentration to decrease by one half. |
| Apparent Clearance (CL/F) of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | Cohorts 1-3: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 28, Cycle 1 Day 29, Cycle 2 Days 1, 15, 21; Cohorts 4-6A: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22, Cycle 2 Days 1, 15, 21 | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. |
| Accumulation Ratio of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | Cohorts 1-3: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Days 8 and 28, Cycle 1 Days 9, 29; Cohorts 4-6A: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Days 1 and 21, Cycle 1 Days 2, 22 | Accumulation ratio was calculated as: AUC0-24 at Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) divided by AUC0-24 at Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3). |
| Tmax of Pictilisib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | Cohorts 1-3: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 8, Cycle 1 Day 9, 15, 21; Cohorts 4-6A: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Day 2, 8, 14 | — |
| Cmax of Pictilisib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | Cohorts 1-3: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 8, Cycle 1 Day 9, 15, 21; Cohorts 4-6A: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Day 2, 8, 14 | — |
| Cmax of Cobimetinib on Cycle 1 Day 1 - Stage 1A All Cohorts | Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 15-17 | — |
| Tmax of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | Cohorts 1-3: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 28, Cycle 1 Day 29, Cycle 2 Days 1, 15, 21; Cohorts 4-6A: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22, Cycle 2 Days 1, 15, 21 | — |
| Cmax of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | Cohorts 1-3: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 28, Cycle 1 Day 29, Cycle 2 Days 1, 15, 21; Cohorts 4-6A: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22, Cycle 2 Days 1, 15, 21 | — |
| AUC0-24 of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | Cohorts 1-3: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 28, Cycle 1 Day 29; Cohorts 4-6A: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22 | — |
| t1/2 of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | Cohorts 1-3: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 28, Cycle 1 Day 29, Cycle 2 Days 1, 15, 21; Cohorts 4-6A: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22, Cycle 2 Days 1, 15, 21 | Half-life is the time measured for the plasma concentration to decrease by one half. As planned, summary statistics were not derived if fewer than 3 participants had available data; however, if the number of participants analyzed = 1, then the observed data of the single participant was reported as geometric mean. |
| CL/F of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | Cohorts 1-3: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 28, Cycle 1 Day 29, Cycle 2 Days 1, 15, 21; Cohorts 4-6A: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22, Cycle 2 Days 1, 15, 21 | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. |
| Accumulation Ratio of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | Cohorts 1-3: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Days 8 and 28, Cycle 1 Days 9, 29; Cohorts 4-6A: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Days 1 and 21, Cycle 1 Day 2, 22 | Accumulation ratio was calculated as: AUC0-24 at Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) divided by AUC0-24 at Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3). |
| Tmax of Cobimetinib on Cycle 1 Day 1 - Stage 1A All Cohorts | Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 15-17 | — |
| Cmax of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21 | — |
| AUC0-24 of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 18, Cycle 1 Day 19 | — |
| t1/2 of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21 | Half-life is the time measured for the plasma concentration to decrease by one half. |
| CL/F of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21 | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. |
| Accumulation Ratio of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Days 1 and 18, Cycle 1 Days 2, 19 | Accumulation ratio was calculated as: AUC0-24 at Cycle 1 Day 18 divided by AUC0-24 at Cycle 1 Day 1. |
| Tmax of Pictilisib on Cycle 1 Day 1 - Stage 1A All Cohorts | Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 15-17 | — |
| Cmax of Pictilisib on Cycle 1 Day 1 - Stage 1A All Cohorts | Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 15-17 | — |
| AUC0-24 of Pictilisib on Cycle 1 Day 1 - Stage 1A All Cohorts | Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Days 2 | — |
| Tmax of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21 | — |
| Cmax of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21 | — |
| AUC0-24 of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 18, Cycle 1 Day 19 | — |
| t1/2 of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21 | Half-life is the time measured for the plasma concentration to decrease by one half. As planned, summary statistics were not derived if fewer than 3 participants had available data; however, if the number of participants analyzed = 1, then the observed data of the single participant was reported as geometric mean. |
| CL/F of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21 | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. |
| Tmax of Cobimetinib on Cycle 1 Day 21 - Stage 1B All Cohorts | Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22 | — |
| Cmax of Cobimetinib on Cycle 1 Day 21 - Stage 1B All Cohorts | Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22 | — |
| AUC0-24 of Cobimetinib on Cycle 1 Day 21 - Stage 1B All Cohorts | Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22 | — |
| CL/F of Cobimetinib on Cycle 1 Day 21 - Stage 1B All Cohorts | Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22 | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. |
| Accumulation Ratio of Cobimetinib on Cycle 1 Day 21 - Stage 1B All Cohorts | Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Days 1 and 21, Cycle 1 Days 2 and 22 | Accumulation ratio was calculated as: AUC0-24 at Cycle 1 Day 21 divided by AUC0-24 at Cycle 1 Day 1. |
| Tmax of Pictilisib on Cycle 1 Day 1 - Stage 1B All Cohorts | Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Day 2 | — |
| Cmax of Pictilisib on Cycle 1 Day 1 - Stage 1B All Cohorts | Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Day 2 | — |
| AUC0-24 of Pictilisib on Cycle 1 Day 1 - Stage 1B All Cohorts | Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Day 2 | — |
| Tmax of Pictilisib on Cycle 1 Day 21 - Stage 1B All Cohorts | Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22 | — |
| Cmax of Pictilisib on Cycle 1 Day 21 - Stage 1B All Cohorts | Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22 | — |
| AUC0-24 of Pictilisib on Cycle 1 Day 21 - Stage 1B All Cohorts | Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22 | — |
| CL/F of Pictilisib on Cycle 1 Day 21 - Stage 1B All Cohorts | Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22 | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. |
| Accumulation Ratio of Pictilisib on Cycle 1 Day 21 - Stage 1B All Cohorts | Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Days 1 and 21, Cycle 1 Days 2 and 22 | Accumulation ratio was calculated as: AUC0-24 at Cycle 1 Day 21 divided by AUC0-24 at Cycle 1 Day 1. |
| Tmax of Cobimetinib on Cycle 1 Day 1 - Stage 2 Individual Indication Specific Cohorts | Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 14 | Stage 2 PK data were reported for each indication specific cohort separately. |
| Cmax of Cobimetinib on Cycle 1 Day 1 - Stage 2 Individual Indication Specific Cohorts | Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 14 | Stage 2 PK data were reported for each indication specific cohort separately. |
| AUC0-24 of Cobimetinib on Cycle 1 Day 1 - Stage 2 All Cohorts | Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Days 2 | Stage 2 PK data were reported for each indication specific cohort separately. |
| Tmax of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22, Cycle 2 Days 1, 15, 21 | Stage 2 PK data were reported for each indication specific cohort separately. |
| Cmax of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22, Cycle 2 Days 1, 15, 21 | Stage 2 PK data were reported for each indication specific cohort separately. |
| AUC0-24 of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22 | Stage 2 PK data were reported for each indication specific cohort separately. |
| t1/2 of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22 | Stage 2 PK data were reported for each indication specific cohort separately. Half-life is the time measured for the plasma concentration to decrease by one half. |
| CL/F of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22, Cycle 2 Days 1, 15, 21 | Stage 2 PK data were reported for each indication specific cohort separately. Half-life is the time measured for the plasma concentration to decrease by one half. Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. |
| Accumulation Ratio of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Days 1 and 21, Cycle 1 Days 2 and 22 | Stage 2 PK data were reported for each indication specific cohort separately. Accumulation ratio was calculated as: AUC0-24 at Cycle 1 Day 21 divided by AUC0-24 at Cycle 1 Day 1. |
| Tmax of Pictilisib on Cycle 1 Day 1 - Stage 2 Individual Indication Specific Cohorts | Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 14 | Stage 2 PK data were reported for each indication specific cohort separately. |
| Cmax of Pictilisib on Cycle 1 Day 1 - Stage 2 Individual Indication Specific Cohorts | Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 14 | Stage 2 PK data were reported for each indication specific cohort separately. |
| AUC0-24 of Pictilisib on Cycle 1 Day 1 - Stage 2 Individual Indication Specific Cohorts | Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Days 2 | Stage 2 PK data were reported for each indication specific cohort separately. |
| Tmax of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22, Cycle 2 Days 1, 15, 21 | Stage 2 PK data were reported for each indication specific cohort separately. |
| Cmax of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22, Cycle 2 Days 1, 15, 21 | Stage 2 PK data were reported for each indication specific cohort separately. |
| AUC0-24 of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22 | Stage 2 PK data were reported for each indication specific cohort separately. |
| t1/2 of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22, Cycle 2 Days 1, 15, 21 | Stage 2 PK data were reported for each indication specific cohort separately. Half-life is the time measured for the plasma concentration to decrease by one half. |
| CL/F of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22, Cycle 2 Days 1, 15, 21 | Stage 2 PK data were reported for each indication specific cohort separately. Half-life is the time measured for the plasma concentration to decrease by one half. Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. |
| Accumulation Ratio of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Days 1 and 21, Cycle 1 Days 2 and 22 | Stage 2 PK data were reported for each indication specific cohort separately. Accumulation ratio was calculated as: AUC0-24 at Cycle 1 Day 21 divided by AUC0-24 at Cycle 1 Day 1. |
| Tmax of Cobimetinib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts | Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 15-17 | Stage 2A PK data were reported for each indication specific cohort separately. |
| Cmax of Cobimetinib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts | Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 15-17 | Stage 2A PK data were reported for each indication specific cohort separately. |
| AUC0-24 of Cobimetinib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts | Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Days 2 | Stage 2A PK data were reported for each indication specific cohort separately. |
| Tmax of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21 | Stage 2A PK data were reported for each indication specific cohort separately. As planned, summary statistics were not derived if fewer than 3 participants had available data; however, if the number of participants analyzed = 1, then the observed data of the single participant was reported as median. |
| Cmax of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21 | Stage 2A PK data were reported for each indication specific cohort separately. As planned, summary statistics were not derived if fewer than 3 participants had available data; however, if the number of participants analyzed = 1, then the observed data of the single participant was reported as geometric mean. |
| AUC0-24 of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21 | Stage 2A PK data were reported for each indication specific cohort separately. As planned, summary statistics were not derived if fewer than 3 participants had available data; however, if the number of participants analyzed = 1, then the observed data of the single participant was reported as geometric mean. |
| t1/2 of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21 | Stage 2A PK data were reported for each indication specific cohort separately. Half-life is the time measured for the plasma concentration to decrease by one half. As planned, summary statistics were not derived if fewer than 3 participants had available data; however, if the number of participants analyzed = 1, then the observed data of the single participant was reported as geometric mean. |
| CL/F of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21 | Stage 2A PK data were reported for each indication specific cohort separately. Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. As planned, summary statistics were not derived if fewer than 3 participants had available data; however, if the number of participants analyzed = 1, then the observed data of the single participant was reported as geometric mean. |
| Accumulation Ratio of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21 | Stage 2A PK data were reported for each indication specific cohort separately. Accumulation ratio was calculated as: AUC0-24 at Cycle 1 Day 21 divided by AUC0-24 at Cycle 1 Day 1. As planned, summary statistics were not derived if fewer than 3 participants had available data; however, if the number of participants analyzed = 1, then the observed data of the single participant was reported as geometric mean. |
| Tmax of Pictilisib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts | Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 15-17 | Stage 2A PK data were reported for each indication specific cohort separately. |
| Cmax of Pictilisib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts | Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 15-17 | Stage 2A PK data were reported for each indication specific cohort separately. |
| AUC0-24 of Pictilisib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts | Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Days 2 | Stage 2A PK data were reported for each indication specific cohort separately. |
| Tmax of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21 | Stage 2A PK data were reported for each indication specific cohort separately. As planned, summary statistics were not derived if fewer than 3 participants had available data; however, if the number of participants analyzed = 1, then the observed data of the single participant was reported as geometric mean. |
| Cmax of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21 | Stage 2A PK data were reported for each indication specific cohort separately. As planned, summary statistics were not derived if fewer than 3 participants had available data; however, if the number of participants analyzed = 1, then the observed data of the single participant was reported as geometric mean. |
| AUC0-24 of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21 | Stage 2A PK data were reported for each indication specific cohort separately. As planned, summary statistics were not derived if fewer than 3 participants had available data; however, if the number of participants analyzed = 1, then the observed data of the single participant was reported as geometric mean. |
| t1/2 of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21 | Stage 2A PK data were reported for each indication specific cohort separately. Half-life is the time measured for the plasma concentration to decrease by one half. |
| AUC0-24 of Cobimetinib on Cycle 1 Day 1 - Stage 1A All Cohorts | Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Days 2 | — |
| Accumulation Ratio of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21 | Stage 2A PK data were reported for each indication specific cohort separately. Accumulation ratio was calculated as: AUC0-24 at Cycle 1 Day 21 divided by AUC0-24 at Cycle 1 Day 1. As planned, summary statistics were not derived if fewer than 3 participants had available data; however, if the number of participants analyzed = 1, then the observed data of the single participant was reported as geometric mean. |
| Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | Up to 30 days after last dose (last dose = up to Cycle 15, cycle length = 28 days) | Tumor response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) = disappearance of all target and non-target lesions. Partial Response (PR) = at least 30 percent (%) decrease in sum of the longest diameter of measured lesions taking as reference the baseline sum of the longest diameter. Progressive disease (PD) = at least 20% increase in the sum of the longest diameter of measured lesions taking as reference the smallest sum of the longest diameter since treatment start or appearance of one or more new lesions. Stable disease (SD) = neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of the longest diameter since treatment start. |
| Duration of Objective Response - Dose Escalation Stages 1, 1A and 1B | Up to 30 days after last dose (last dose = up to Cycle 15, cycle length = 28 days) | Duration of objective response was defined as the time from first occurrence of a documented objective response (CR or PR) until the time of disease progression, as determined by investigator review of tumor assessments using RECIST, or death from any cause during the study (within 30 days after the last dose of study treatment). CR = disappearance of all target and non-target lesions. PR = at least 30 % decrease in sum of the longest diameter of measured lesions taking as reference the baseline sum of the longest diameter. PD = at least 20% increase in the sum of the longest diameter of measured lesions taking as reference the smallest sum of the longest diameter since treatment start or appearance of one or more new lesions. |
| Progression-Free Survival (PFS) - Dose Escalation Stages 1, 1A and 1B | Up to 30 days after last dose (last dose = up to Cycle 15, cycle length = 28 days) | PFS was the time from study treatment initiation to the first occurrence of disease progression, as determined by investigator review of tumor assessments using RECIST, or death from any cause during the study (within 30 days after the last dose of study treatment). PD = at least 20% increase in the sum of the longest diameter of measured lesions taking as reference the smallest sum of the longest diameter since treatment start or appearance of one or more new lesions. |
| CL/F of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21 | Stage 2A PK data were reported for each indication specific cohort separately. Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. As planned, summary statistics were not derived if fewer than 3 participants had available data; however, if the number of participants analyzed = 1, then the observed data of the single participant was reported as geometric mean. |
| Tmax of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21 | — |
| Tmax of Cobimetinib on Cycle 1 Day 1 - Stage 1B All Cohorts | Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Day 2 | — |
| Cmax of Cobimetinib on Cycle 1 Day 1 - Stage 1B All Cohorts | Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Day 2 | — |
| AUC0-24 of Cobimetinib on Cycle 1 Day 1 - Stage 1B All Cohorts | Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Day 2 | — |
| Tmax of Cobimetinib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | Cohorts 1-3: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 8, Cycle 1 Days 9, 15, 21; Cohorts 4-6A: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Day 2, 8, 14 | — |
| Cmax of Cobimetinib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | Cohorts 1-3: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 8, Cycle 1 Days 9, 15, 21; Cohorts 4-6A: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Day 2, 8, 14 | — |
| AUC0-24 of Cobimetinib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | Cohorts 1-3: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 8, Cycle 1 Days 9; Cohorts 4-6A: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Day 2 | — |
Countries
United States
Participant flow
Pre-assignment details
Study was terminated before initiation of Stage 2B; hence Stage 2B cohorts were not applicable.
Participants by arm
| Arm | Count |
|---|---|
| All Participants All participants who received cobimetinib and pictilisib in any dose combination until disease progression, unacceptable toxicity, or any other discontinuation criterion was met. | 178 |
| Total | 178 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 | FG016 | FG017 | FG018 | FG019 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Dose-Escalation Stage 1 | Adverse Event | 0 | 0 | 0 | 2 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose-Escalation Stage 1 | Death | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose-Escalation Stage 1 | Disease Progression | 2 | 2 | 3 | 4 | 10 | 7 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose-Escalation Stage 1 | Physician Decision | 1 | 0 | 0 | 1 | 0 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose-Escalation Stage 1 | Withdrawal by Subject | 0 | 1 | 0 | 2 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose-Escalation Stage 1A | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose-Escalation Stage 1A | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose-Escalation Stage 1A | Disease Progression | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 3 | 1 | 5 | 7 | 6 | 4 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose-Escalation Stage 1A | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose-Escalation Stage 1A | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose-Escalation Stage 1B | Disease Progression | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 3 | 3 | 3 | 0 | 0 |
| Dose-Escalation Stage 1B | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 |
| Expansion Stage 2 | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 0 |
| Expansion Stage 2 | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 |
| Expansion Stage 2 | Disease Progression | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 28 | 0 |
| Expansion Stage 2 | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Expansion Stage 2 | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Expansion Stage 2A | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 8 |
| Expansion Stage 2A | Disease Progression | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 31 |
| Expansion Stage 2A | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 |
| Expansion Stage 2A | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 4 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 56.6 years STANDARD_DEVIATION 12 |
| Gender Female | 109 Participants |
| Gender Male | 69 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 4 | 3 / 3 | 3 / 3 | 42 / 43 | 11 / 11 | 10 / 10 | 4 / 4 | 3 / 3 | 3 / 3 | 4 / 4 | 52 / 52 | 9 / 9 | 8 / 8 | 5 / 5 | 4 / 4 | 3 / 3 | 3 / 3 | 5 / 5 |
| serious Total, serious adverse events | 2 / 4 | 0 / 3 | 1 / 3 | 25 / 43 | 6 / 11 | 6 / 10 | 2 / 4 | 2 / 3 | 2 / 3 | 3 / 4 | 28 / 52 | 4 / 9 | 5 / 8 | 3 / 5 | 0 / 4 | 0 / 3 | 0 / 3 | 2 / 5 |
Outcome results
Primary
Area Under the Concentration-Time Curve From Time 0 to 24 Hours Post-Dose (AUC0-24) of Cobimetinib on Day 3 - Stage 1, Cohorts 1-3
Time frame: 0-4 hours Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Day 3, Day 4
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Area Under the Concentration-Time Curve From Time 0 to 24 Hours Post-Dose (AUC0-24) of Cobimetinib on Day 3 - Stage 1, Cohorts 1-3 | 392 nonograms*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 88 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Area Under the Concentration-Time Curve From Time 0 to 24 Hours Post-Dose (AUC0-24) of Cobimetinib on Day 3 - Stage 1, Cohorts 1-3 | 279 nonograms*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 75 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Area Under the Concentration-Time Curve From Time 0 to 24 Hours Post-Dose (AUC0-24) of Cobimetinib on Day 3 - Stage 1, Cohorts 1-3 | 1190 nonograms*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 53 |
Primary
AUC0-24 of Pictilisib on Day 1 - Stage 1, Cohorts 1-3
Time frame: 0-4 hours Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Day 1, Day 2, 0-4 hours Pr-C dose on Day 3
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | AUC0-24 of Pictilisib on Day 1 - Stage 1, Cohorts 1-3 | 1680 ng*h/mL | Geometric Coefficient of Variation 16 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Pictilisib on Day 1 - Stage 1, Cohorts 1-3 | 1950 ng*h/mL | Geometric Coefficient of Variation 50 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | AUC0-24 of Pictilisib on Day 1 - Stage 1, Cohorts 1-3 | 2680 ng*h/mL | Geometric Coefficient of Variation 83 |
Primary
Cmax of Pictilisib on Day 1 - Stage 1, Cohorts 1-3
Time frame: 0-4 hours Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Day 1, Day 2, 0-4 hours Pr-C dose on Day 3
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Cmax of Pictilisib on Day 1 - Stage 1, Cohorts 1-3 | 162 ng/mL | Geometric Coefficient of Variation 37 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Cmax of Pictilisib on Day 1 - Stage 1, Cohorts 1-3 | 185 ng/mL | Geometric Coefficient of Variation 27 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Cmax of Pictilisib on Day 1 - Stage 1, Cohorts 1-3 | 280 ng/mL | Geometric Coefficient of Variation 41 |
Primary
Maximum Plasma Concentration (Cmax) of Cobimetinib on Day 3 - Stage 1, Cohorts 1-3
Time frame: 0-4 hours Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Day 3, Day 4
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Maximum Plasma Concentration (Cmax) of Cobimetinib on Day 3 - Stage 1, Cohorts 1-3 | 27.6 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 95 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Maximum Plasma Concentration (Cmax) of Cobimetinib on Day 3 - Stage 1, Cohorts 1-3 | 16.6 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 78 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Maximum Plasma Concentration (Cmax) of Cobimetinib on Day 3 - Stage 1, Cohorts 1-3 | 97.0 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 63 |
Primary
Maximum Tolerated Combination Doses of Cobimetinib and Pictilisib During Dose-Escalation Stages 1, 1A and 1B
MTD was determined (by Investigator) based on the DLTs, as well as adverse events (AEs) in dose-escalation Stages 1, 1A, and 1B that did not meet protocol-defined DLT criteria but indicated intolerability of a given dose combination. Separate combination MTDs were determined for each dose-escalation stage. DLT was defined as 1 of the following toxicities considered treatment related by Investigator: Grade ≥3 non-hematologic, non-hepatic organ toxicity; Grade ≥3 febrile neutropenia; Grade ≥4 neutropenia (absolute neutrophil count \<500/microliter) lasting \>5 days; Grade ≥4 thrombocytopenia lasting \>48 hours; Grade ≥4 anemia; Grade ≥3 total bilirubin, hepatic transaminase, alkaline phosphatase, lasting \>72 hours; Grade ≥2 diffusion capacity of the lung for carbon monoxide concomitant with an absolute decrease of ≥20 percentage points from baseline.
Time frame: Cohorts 1-3: Day 1 to Day 35, All other cohorts: Day 1 to Day 28
Population: Safety-evaluable population. Here, number of participants analyzed = participants who were evaluable for this outcome and n = participants evaluable for specified categories.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Maximum Tolerated Combination Doses of Cobimetinib and Pictilisib During Dose-Escalation Stages 1, 1A and 1B | Stage 1B: Cobimetinib (n = 20) | NA mg |
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Maximum Tolerated Combination Doses of Cobimetinib and Pictilisib During Dose-Escalation Stages 1, 1A and 1B | Stage 1B: Pictilisib (n = 20) | NA mg |
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Maximum Tolerated Combination Doses of Cobimetinib and Pictilisib During Dose-Escalation Stages 1, 1A and 1B | Stage 1: Cobimetinib (n = 44) | 40 mg |
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Maximum Tolerated Combination Doses of Cobimetinib and Pictilisib During Dose-Escalation Stages 1, 1A and 1B | Stage 1: Pictilisib (n = 44) | 100 mg |
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Maximum Tolerated Combination Doses of Cobimetinib and Pictilisib During Dose-Escalation Stages 1, 1A and 1B | Stage 1A: Cobimetinib (n = 34) | 125 mg |
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Maximum Tolerated Combination Doses of Cobimetinib and Pictilisib During Dose-Escalation Stages 1, 1A and 1B | Stage 1A: Pictilisib (n = 34) | 180 mg |
Primary
Number of Participants With Dose-Limiting Toxicities (DLTs) During Dose Escalation Stages 1, 1A and 1B
DLT was defined as 1 of the following toxicities considered treatment related by Investigator: Grade ≥3 non-hematologic, non-hepatic organ toxicity, excluding the following: Grade 3 nausea, vomiting, or diarrhea that resolved to Grade ≤1 within 7 days, Grade 3 rash or Grade ≥3 fatigue that resolved to Grade ≤2 within 7 days, Grade ≥3 hyperglycemia or lipid profile results that occurred during non-fasting conditions, Grade 3 or 4 elevation of serum creatine phosphokinase levels or Grade 3 non clinically significant (as assessed by Investigator) laboratory abnormality that was asymptomatic; Grade ≥3 febrile neutropenia; Grade ≥4 neutropenia (absolute neutrophil count \<500/microliter) lasting \>5 days; Grade ≥4 thrombocytopenia lasting \>48 hours; Grade ≥4 anemia; Grade ≥3 total bilirubin, hepatic transaminase, alkaline phosphatase, lasting \>72 hours; Grade ≥2 diffusion capacity of the lung for carbon monoxide concomitant with an absolute decrease of ≥20 percentage points from baseline.
Time frame: Cohorts 1-3: Day 1 to Day 35, All other cohorts: Day 1 to Day 28
Population: Safety-evaluable population included all participants who received at least one dose of study drug. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Number of Participants With Dose-Limiting Toxicities (DLTs) During Dose Escalation Stages 1, 1A and 1B | 0 participants |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Number of Participants With Dose-Limiting Toxicities (DLTs) During Dose Escalation Stages 1, 1A and 1B | 0 participants |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Number of Participants With Dose-Limiting Toxicities (DLTs) During Dose Escalation Stages 1, 1A and 1B | 0 participants |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Number of Participants With Dose-Limiting Toxicities (DLTs) During Dose Escalation Stages 1, 1A and 1B | 1 participants |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | Number of Participants With Dose-Limiting Toxicities (DLTs) During Dose Escalation Stages 1, 1A and 1B | 1 participants |
| S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib | Number of Participants With Dose-Limiting Toxicities (DLTs) During Dose Escalation Stages 1, 1A and 1B | 0 participants |
| S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib | Number of Participants With Dose-Limiting Toxicities (DLTs) During Dose Escalation Stages 1, 1A and 1B | 0 participants |
| S1A CA: 100 mg Cobimetinib + 130 mg Pictilisib | Number of Participants With Dose-Limiting Toxicities (DLTs) During Dose Escalation Stages 1, 1A and 1B | 0 participants |
| S1A CB: 100 mg Cobimetinib + 180 mg Pictilisib | Number of Participants With Dose-Limiting Toxicities (DLTs) During Dose Escalation Stages 1, 1A and 1B | 0 participants |
| S1A CC: 125 mg Cobimetinib + 130 mg Pictilisib | Number of Participants With Dose-Limiting Toxicities (DLTs) During Dose Escalation Stages 1, 1A and 1B | 0 participants |
| S1A CD: 125 mg Cobimetinib + 180 mg Pictilisib | Number of Participants With Dose-Limiting Toxicities (DLTs) During Dose Escalation Stages 1, 1A and 1B | 0 participants |
| S1A CE: 125 mg Cobimetinib + 245 mg Pictilisib | Number of Participants With Dose-Limiting Toxicities (DLTs) During Dose Escalation Stages 1, 1A and 1B | 0 participants |
| S1A CF: 150 mg Cobimetinib + 180 mg Pictilisib | Number of Participants With Dose-Limiting Toxicities (DLTs) During Dose Escalation Stages 1, 1A and 1B | 1 participants |
| S1A CG: 150 mg Cobimetinib + 245 mg Pictilisib | Number of Participants With Dose-Limiting Toxicities (DLTs) During Dose Escalation Stages 1, 1A and 1B | 2 participants |
| S1B CAX: 40 mg Cobimetinib + 130 mg Pictilisib | Number of Participants With Dose-Limiting Toxicities (DLTs) During Dose Escalation Stages 1, 1A and 1B | 0 participants |
| S1B CBX: 40 mg Cobimetinib + 180 mg Pictilisib | Number of Participants With Dose-Limiting Toxicities (DLTs) During Dose Escalation Stages 1, 1A and 1B | 0 participants |
| S1B CCX: 60 mg Cobimetinib + 130 mg Pictilisib | Number of Participants With Dose-Limiting Toxicities (DLTs) During Dose Escalation Stages 1, 1A and 1B | 0 participants |
| S1B CDX: 60 mg Cobimetinib + 180 mg Pictilisib | Number of Participants With Dose-Limiting Toxicities (DLTs) During Dose Escalation Stages 1, 1A and 1B | 1 participants |
Primary
Time of Maximum Concentration (Tmax) of Cobimetinib on Day 3 - Stage 1, Cohorts 1-3
Time frame: 0-4 hours pre-cobimetinib (Pr-C) dose, 0.5, 2, 4, 6 hours post-cobimetinib (Po-C) dose on Day 3, Day 4
Population: Pharmacokinetic (PK) population included all participants who had at least one cobimetinib and pictilisib plasma concentration available. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Time of Maximum Concentration (Tmax) of Cobimetinib on Day 3 - Stage 1, Cohorts 1-3 | 4.00 hours |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Time of Maximum Concentration (Tmax) of Cobimetinib on Day 3 - Stage 1, Cohorts 1-3 | 4.00 hours |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Time of Maximum Concentration (Tmax) of Cobimetinib on Day 3 - Stage 1, Cohorts 1-3 | 2.00 hours |
Primary
Tmax of Pictilisib on Day 1 - Stage 1, Cohorts 1-3
Time frame: 0-4 hours pre-pictilisib (Pr-P) dose, 0.5, 2, 4, 6 hours post-pictilisib (Po-P) dose on Day 1, Day 2, 0-4 hours Pr-C dose on Day 3
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Tmax of Pictilisib on Day 1 - Stage 1, Cohorts 1-3 | 3.00 hours |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Tmax of Pictilisib on Day 1 - Stage 1, Cohorts 1-3 | 4.00 hours |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Tmax of Pictilisib on Day 1 - Stage 1, Cohorts 1-3 | 2.00 hours |
Secondary
Accumulation Ratio of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts
Accumulation ratio was calculated as: AUC0-24 at Cycle 1 Day 18 divided by AUC0-24 at Cycle 1 Day 1.
Time frame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Days 1 and 18, Cycle 1 Days 2, 19
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Accumulation Ratio of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | 2.70 ratio | Geometric Coefficient of Variation 57 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Accumulation Ratio of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | 2.44 ratio | Geometric Coefficient of Variation 60 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Accumulation Ratio of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | 1.46 ratio | Geometric Coefficient of Variation 30 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Accumulation Ratio of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | 1.11 ratio | Geometric Coefficient of Variation 67 |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | Accumulation Ratio of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | 1.52 ratio | Geometric Coefficient of Variation 120 |
| S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib | Accumulation Ratio of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | 1.75 ratio | Geometric Coefficient of Variation 40 |
| S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib | Accumulation Ratio of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | 1.84 ratio | Geometric Coefficient of Variation 8.1 |
Secondary
Accumulation Ratio of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts
Stage 2A PK data were reported for each indication specific cohort separately. Accumulation ratio was calculated as: AUC0-24 at Cycle 1 Day 21 divided by AUC0-24 at Cycle 1 Day 1. As planned, summary statistics were not derived if fewer than 3 participants had available data; however, if the number of participants analyzed = 1, then the observed data of the single participant was reported as geometric mean.
Time frame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Accumulation Ratio of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 1.46 ng*h/mL | — |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Accumulation Ratio of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 1.43 ng*h/mL | Geometric Coefficient of Variation 51 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Accumulation Ratio of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 1.89 ng*h/mL | Geometric Coefficient of Variation 94 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Accumulation Ratio of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 1.72 ng*h/mL | Geometric Coefficient of Variation 83 |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | Accumulation Ratio of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | NA ng*h/mL | — |
Secondary
Accumulation Ratio of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts
Accumulation ratio was calculated as: AUC0-24 at Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) divided by AUC0-24 at Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3).
Time frame: Cohorts 1-3: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Days 8 and 28, Cycle 1 Days 9, 29; Cohorts 4-6A: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Days 1 and 21, Cycle 1 Days 2, 22
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Accumulation Ratio of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 2.51 ratio | Geometric Coefficient of Variation 63 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Accumulation Ratio of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 2.89 ratio | Geometric Coefficient of Variation 43 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Accumulation Ratio of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 3.14 ratio | Geometric Coefficient of Variation 73 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Accumulation Ratio of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 2.03 ratio | Geometric Coefficient of Variation 36 |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | Accumulation Ratio of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 2.90 ratio | Geometric Coefficient of Variation 73 |
| S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib | Accumulation Ratio of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 2.83 ratio | Geometric Coefficient of Variation 54 |
| S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib | Accumulation Ratio of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 1.77 ratio | — |
Secondary
Accumulation Ratio of Cobimetinib on Cycle 1 Day 21 - Stage 1B All Cohorts
Accumulation ratio was calculated as: AUC0-24 at Cycle 1 Day 21 divided by AUC0-24 at Cycle 1 Day 1.
Time frame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Days 1 and 21, Cycle 1 Days 2 and 22
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Accumulation Ratio of Cobimetinib on Cycle 1 Day 21 - Stage 1B All Cohorts | 3.82 ratio | Geometric Coefficient of Variation 60 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Accumulation Ratio of Cobimetinib on Cycle 1 Day 21 - Stage 1B All Cohorts | 2.46 ratio | Geometric Coefficient of Variation 46 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Accumulation Ratio of Cobimetinib on Cycle 1 Day 21 - Stage 1B All Cohorts | NA ratio | — |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Accumulation Ratio of Cobimetinib on Cycle 1 Day 21 - Stage 1B All Cohorts | 1.15 ratio | Geometric Coefficient of Variation 57 |
Secondary
Accumulation Ratio of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts
Stage 2 PK data were reported for each indication specific cohort separately. Accumulation ratio was calculated as: AUC0-24 at Cycle 1 Day 21 divided by AUC0-24 at Cycle 1 Day 1.
Time frame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Days 1 and 21, Cycle 1 Days 2 and 22
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Accumulation Ratio of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | 1.92 ratio | Geometric Coefficient of Variation 51 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Accumulation Ratio of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | 3.28 ratio | Geometric Coefficient of Variation 52 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Accumulation Ratio of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | 2.60 ratio | Geometric Coefficient of Variation 63 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Accumulation Ratio of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | NA ratio | — |
Secondary
Accumulation Ratio of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts
Accumulation ratio was calculated as: AUC0-24 at Cycle 1 Day 18 divided by AUC0-24 at Cycle 1 Day 1.
Time frame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Days 1 and 18, Cycle 1 Days 2, 19
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Accumulation Ratio of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | 1.64 ratio | Geometric Coefficient of Variation 40 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Accumulation Ratio of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | 1.57 ratio | Geometric Coefficient of Variation 45 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Accumulation Ratio of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | 1.89 ratio | Geometric Coefficient of Variation 110 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Accumulation Ratio of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | 1.15 ratio | Geometric Coefficient of Variation 55 |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | Accumulation Ratio of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | 1.56 ratio | Geometric Coefficient of Variation 42 |
| S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib | Accumulation Ratio of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | 1.60 ratio | Geometric Coefficient of Variation 100 |
| S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib | Accumulation Ratio of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | 1.46 ratio | Geometric Coefficient of Variation 100 |
Secondary
Accumulation Ratio of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts
Stage 2A PK data were reported for each indication specific cohort separately. Accumulation ratio was calculated as: AUC0-24 at Cycle 1 Day 21 divided by AUC0-24 at Cycle 1 Day 1. As planned, summary statistics were not derived if fewer than 3 participants had available data; however, if the number of participants analyzed = 1, then the observed data of the single participant was reported as geometric mean.
Time frame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Accumulation Ratio of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 0.78 ng*h/mL | — |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Accumulation Ratio of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 1.61 ng*h/mL | Geometric Coefficient of Variation 110 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Accumulation Ratio of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 1.90 ng*h/mL | Geometric Coefficient of Variation 50 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Accumulation Ratio of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 1.03 ng*h/mL | Geometric Coefficient of Variation 84 |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | Accumulation Ratio of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | NA ng*h/mL | — |
Secondary
Accumulation Ratio of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts
Accumulation ratio was calculated as: AUC0-24 at Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) divided by AUC0-24 at Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3).
Time frame: Cohorts 1-3: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Days 8 and 28, Cycle 1 Days 9, 29; Cohorts 4-6A: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Days 1 and 21, Cycle 1 Day 2, 22
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Accumulation Ratio of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 1.51 ratio | Geometric Coefficient of Variation 47 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Accumulation Ratio of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 1.36 ratio | Geometric Coefficient of Variation 79 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Accumulation Ratio of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 2.11 ratio | Geometric Coefficient of Variation 6 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Accumulation Ratio of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 1.16 ratio | Geometric Coefficient of Variation 34 |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | Accumulation Ratio of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 1.71 ratio | Geometric Coefficient of Variation 29 |
| S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib | Accumulation Ratio of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 1.70 ratio | Geometric Coefficient of Variation 25 |
| S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib | Accumulation Ratio of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 2.8 ratio | — |
Secondary
Accumulation Ratio of Pictilisib on Cycle 1 Day 21 - Stage 1B All Cohorts
Accumulation ratio was calculated as: AUC0-24 at Cycle 1 Day 21 divided by AUC0-24 at Cycle 1 Day 1.
Time frame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Days 1 and 21, Cycle 1 Days 2 and 22
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Accumulation Ratio of Pictilisib on Cycle 1 Day 21 - Stage 1B All Cohorts | 1.30 ratio | Geometric Coefficient of Variation 40 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Accumulation Ratio of Pictilisib on Cycle 1 Day 21 - Stage 1B All Cohorts | 2.06 ratio | Geometric Coefficient of Variation 19 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Accumulation Ratio of Pictilisib on Cycle 1 Day 21 - Stage 1B All Cohorts | NA ratio | — |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Accumulation Ratio of Pictilisib on Cycle 1 Day 21 - Stage 1B All Cohorts | 1.36 ratio | Geometric Coefficient of Variation 57 |
Secondary
Accumulation Ratio of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts
Stage 2 PK data were reported for each indication specific cohort separately. Accumulation ratio was calculated as: AUC0-24 at Cycle 1 Day 21 divided by AUC0-24 at Cycle 1 Day 1.
Time frame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Days 1 and 21, Cycle 1 Days 2 and 22
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Accumulation Ratio of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | 0.90 ratio | Geometric Coefficient of Variation 40 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Accumulation Ratio of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | 1.39 ratio | Geometric Coefficient of Variation 58 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Accumulation Ratio of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | 1.43 ratio | Geometric Coefficient of Variation 57 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Accumulation Ratio of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | NA ratio | — |
Secondary
Apparent Clearance (CL/F) of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Time frame: Cohorts 1-3: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 28, Cycle 1 Day 29, Cycle 2 Days 1, 15, 21; Cohorts 4-6A: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22, Cycle 2 Days 1, 15, 21
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Apparent Clearance (CL/F) of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 26.7 Liters per hour (L/hr) | Geometric Coefficient of Variation 1.4 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Apparent Clearance (CL/F) of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 22.2 Liters per hour (L/hr) | Geometric Coefficient of Variation 70 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Apparent Clearance (CL/F) of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 9.67 Liters per hour (L/hr) | Geometric Coefficient of Variation 94 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Apparent Clearance (CL/F) of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 16.6 Liters per hour (L/hr) | Geometric Coefficient of Variation 66 |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | Apparent Clearance (CL/F) of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 16.2 Liters per hour (L/hr) | Geometric Coefficient of Variation 61 |
| S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib | Apparent Clearance (CL/F) of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 14.8 Liters per hour (L/hr) | Geometric Coefficient of Variation 110 |
| S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib | Apparent Clearance (CL/F) of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 53.6 Liters per hour (L/hr) | — |
Secondary
AUC0-24 of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts
Time frame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 18, Cycle 1 Day 19
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | 13400 ng*h/mL | Geometric Coefficient of Variation 18 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | 5680 ng*h/mL | Geometric Coefficient of Variation 55 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | 9990 ng*h/mL | Geometric Coefficient of Variation 28 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | 3060 ng*h/mL | Geometric Coefficient of Variation 50 |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | 6980 ng*h/mL | Geometric Coefficient of Variation 55 |
| S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | 7740 ng*h/mL | Geometric Coefficient of Variation 69 |
| S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | 11100 ng*h/mL | Geometric Coefficient of Variation 23 |
Secondary
AUC0-24 of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts
Stage 2A PK data were reported for each indication specific cohort separately. As planned, summary statistics were not derived if fewer than 3 participants had available data; however, if the number of participants analyzed = 1, then the observed data of the single participant was reported as geometric mean.
Time frame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 9560 ng*h/mL | — |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 7920 ng*h/mL | Geometric Coefficient of Variation 16 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 7390 ng*h/mL | Geometric Coefficient of Variation 32 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 5790 ng*h/mL | Geometric Coefficient of Variation 46 |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | NA ng*h/mL | — |
Secondary
AUC0-24 of Cobimetinib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts
Time frame: Cohorts 1-3: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 8, Cycle 1 Days 9; Cohorts 4-6A: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Day 2
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | 299 ng*h/mL | Geometric Coefficient of Variation 62 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | 311 ng*h/mL | Geometric Coefficient of Variation 53 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | 1320 ng*h/mL | Geometric Coefficient of Variation 56.6 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | 1300 ng*h/mL | Geometric Coefficient of Variation 61 |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | 957 ng*h/mL | Geometric Coefficient of Variation 42 |
| S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | 2050 ng*h/mL | Geometric Coefficient of Variation 71 |
| S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | 1790 ng*h/mL | Geometric Coefficient of Variation 56 |
Secondary
AUC0-24 of Cobimetinib on Cycle 1 Day 1 - Stage 1A All Cohorts
Time frame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Days 2
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 1 - Stage 1A All Cohorts | 4950 ng*h/mL | Geometric Coefficient of Variation 80 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 1 - Stage 1A All Cohorts | 2320 ng*h/mL | Geometric Coefficient of Variation 61 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 1 - Stage 1A All Cohorts | 5520 ng*h/mL | Geometric Coefficient of Variation 59 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 1 - Stage 1A All Cohorts | 2620 ng*h/mL | Geometric Coefficient of Variation 50 |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 1 - Stage 1A All Cohorts | 4250 ng*h/mL | Geometric Coefficient of Variation 75 |
| S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 1 - Stage 1A All Cohorts | 5100 ng*h/mL | Geometric Coefficient of Variation 47 |
| S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 1 - Stage 1A All Cohorts | 5090 ng*h/mL | Geometric Coefficient of Variation 45 |
Secondary
AUC0-24 of Cobimetinib on Cycle 1 Day 1 - Stage 1B All Cohorts
Time frame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Day 2
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 1 - Stage 1B All Cohorts | 855 ng*h/mL | Geometric Coefficient of Variation 150 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 1 - Stage 1B All Cohorts | 1750 ng*h/mL | Geometric Coefficient of Variation 77 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 1 - Stage 1B All Cohorts | 699 ng*h/mL | Geometric Coefficient of Variation 72 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 1 - Stage 1B All Cohorts | 2460 ng*h/mL | — |
Secondary
AUC0-24 of Cobimetinib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts
Stage 2A PK data were reported for each indication specific cohort separately.
Time frame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Days 2
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts | 6560 ng*h/mL | — |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts | 5210 ng*h/mL | Geometric Coefficient of Variation 43 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts | 4470 ng*h/mL | Geometric Coefficient of Variation 120 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts | 4090 ng*h/mL | Geometric Coefficient of Variation 120 |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts | 5630 ng*h/mL | Geometric Coefficient of Variation 90 |
Secondary
AUC0-24 of Cobimetinib on Cycle 1 Day 1 - Stage 2 All Cohorts
Stage 2 PK data were reported for each indication specific cohort separately.
Time frame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Days 2
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 1 - Stage 2 All Cohorts | 1080 ng*h/mL | Geometric Coefficient of Variation 26 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 1 - Stage 2 All Cohorts | 1330 ng*h/mL | Geometric Coefficient of Variation 100 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 1 - Stage 2 All Cohorts | 1790 ng*h/mL | Geometric Coefficient of Variation 73 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 1 - Stage 2 All Cohorts | 700 ng*h/mL | Geometric Coefficient of Variation 84 |
Secondary
AUC0-24 of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts
Time frame: Cohorts 1-3: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 28, Cycle 1 Day 29; Cohorts 4-6A: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 749 ng*h/mL | Geometric Coefficient of Variation 1.4 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 900 ng*h/mL | Geometric Coefficient of Variation 70 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 4130 ng*h/mL | Geometric Coefficient of Variation 94 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 2410 ng*h/mL | Geometric Coefficient of Variation 66 |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 2460 ng*h/mL | Geometric Coefficient of Variation 57 |
| S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 4050 ng*h/mL | Geometric Coefficient of Variation 110 |
| S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 1120 ng*h/mL | — |
Secondary
AUC0-24 of Cobimetinib on Cycle 1 Day 21 - Stage 1B All Cohorts
Time frame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 21 - Stage 1B All Cohorts | 3270 ng*h/mL | Geometric Coefficient of Variation 64 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 21 - Stage 1B All Cohorts | 4320 ng*h/mL | Geometric Coefficient of Variation 150 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 21 - Stage 1B All Cohorts | NA ng*h/mL | — |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 21 - Stage 1B All Cohorts | 4190 ng*h/mL | Geometric Coefficient of Variation 52 |
Secondary
AUC0-24 of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts
Stage 2 PK data were reported for each indication specific cohort separately.
Time frame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | 2200 ng*h/mL | Geometric Coefficient of Variation 57 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | 4570 ng*h/mL | Geometric Coefficient of Variation 68 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | 4700 ng*h/mL | Geometric Coefficient of Variation 120 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | NA ng*h/mL | — |
Secondary
AUC0-24 of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts
Time frame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 18, Cycle 1 Day 19
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | 11300 ng*h/mL | Geometric Coefficient of Variation 21 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | 7680 ng*h/mL | Geometric Coefficient of Variation 88 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | 6990 ng*h/mL | Geometric Coefficient of Variation 38 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | 6120 ng*h/mL | Geometric Coefficient of Variation 110 |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | 12100 ng*h/mL | Geometric Coefficient of Variation 58 |
| S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | 8140 ng*h/mL | Geometric Coefficient of Variation 58 |
| S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | 10100 ng*h/mL | Geometric Coefficient of Variation 44 |
Secondary
AUC0-24 of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts
Stage 2A PK data were reported for each indication specific cohort separately. As planned, summary statistics were not derived if fewer than 3 participants had available data; however, if the number of participants analyzed = 1, then the observed data of the single participant was reported as geometric mean.
Time frame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 6300 ng*h/mL | — |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 6310 ng*h/mL | Geometric Coefficient of Variation 31 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 5930 ng*h/mL | Geometric Coefficient of Variation 73 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 3990 ng*h/mL | Geometric Coefficient of Variation 74 |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | NA ng*h/mL | — |
Secondary
AUC0-24 of Pictilisib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts
Time frame: Cohorts 1-3: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 8, Cycle 1 Day 9; Cohorts 4-6A: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Day 2
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | 1660 ng*h/mL | Geometric Coefficient of Variation 28 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | 2150 ng*h/mL | Geometric Coefficient of Variation 43 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | 2600 ng*h/mL | Geometric Coefficient of Variation 28 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | 3360 ng*h/mL | Geometric Coefficient of Variation 43 |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | 2770 ng*h/mL | Geometric Coefficient of Variation 43 |
| S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | 2870 ng*h/mL | Geometric Coefficient of Variation 48 |
| S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | 3240 ng*h/mL | Geometric Coefficient of Variation 68 |
Secondary
AUC0-24 of Pictilisib on Cycle 1 Day 1 - Stage 1A All Cohorts
Time frame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Days 2
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 1 - Stage 1A All Cohorts | 6900 ng*h/mL | Geometric Coefficient of Variation 62 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 1 - Stage 1A All Cohorts | 4900 ng*h/mL | Geometric Coefficient of Variation 170 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 1 - Stage 1A All Cohorts | 3670 ng*h/mL | Geometric Coefficient of Variation 72 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 1 - Stage 1A All Cohorts | 4280 ng*h/mL | Geometric Coefficient of Variation 48 |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 1 - Stage 1A All Cohorts | 8440 ng*h/mL | Geometric Coefficient of Variation 32 |
| S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 1 - Stage 1A All Cohorts | 5650 ng*h/mL | Geometric Coefficient of Variation 88 |
| S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 1 - Stage 1A All Cohorts | 6680 ng*h/mL | Geometric Coefficient of Variation 53 |
Secondary
AUC0-24 of Pictilisib on Cycle 1 Day 1 - Stage 1B All Cohorts
Time frame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Day 2
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 1 - Stage 1B All Cohorts | 5380 ng*h/mL | Geometric Coefficient of Variation 50 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 1 - Stage 1B All Cohorts | 6540 ng*h/mL | Geometric Coefficient of Variation 20 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 1 - Stage 1B All Cohorts | 2260 ng*h/mL | Geometric Coefficient of Variation 70 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 1 - Stage 1B All Cohorts | 4160 ng*h/mL | Geometric Coefficient of Variation 77 |
Secondary
AUC0-24 of Pictilisib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts
Stage 2A PK data were reported for each indication specific cohort separately.
Time frame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Days 2
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts | 8050 ng*h/mL | — |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts | 3380 ng*h/mL | Geometric Coefficient of Variation 100 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts | 3310 ng*h/mL | Geometric Coefficient of Variation 76 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts | 4030 ng*h/mL | Geometric Coefficient of Variation 88 |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts | 4500 ng*h/mL | Geometric Coefficient of Variation 16 |
Secondary
AUC0-24 of Pictilisib on Cycle 1 Day 1 - Stage 2 Individual Indication Specific Cohorts
Stage 2 PK data were reported for each indication specific cohort separately.
Time frame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Days 2
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 1 - Stage 2 Individual Indication Specific Cohorts | 3010 ng*h/mL | Geometric Coefficient of Variation 37 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 1 - Stage 2 Individual Indication Specific Cohorts | 3800 ng*h/mL | Geometric Coefficient of Variation 63 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 1 - Stage 2 Individual Indication Specific Cohorts | 3210 ng*h/mL | Geometric Coefficient of Variation 59 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 1 - Stage 2 Individual Indication Specific Cohorts | 3340 ng*h/mL | Geometric Coefficient of Variation 78 |
Secondary
AUC0-24 of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts
Time frame: Cohorts 1-3: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 28, Cycle 1 Day 29; Cohorts 4-6A: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 2500 ng*h/mL | Geometric Coefficient of Variation 21 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 2930 ng*h/mL | Geometric Coefficient of Variation 150 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 5500 ng*h/mL | Geometric Coefficient of Variation 34 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 3890 ng*h/mL | Geometric Coefficient of Variation 63 |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 4320 ng*h/mL | Geometric Coefficient of Variation 58 |
| S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 4510 ng*h/mL | Geometric Coefficient of Variation 40 |
| S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 4070 ng*h/mL | — |
Secondary
AUC0-24 of Pictilisib on Cycle 1 Day 21 - Stage 1B All Cohorts
Time frame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 21 - Stage 1B All Cohorts | 7000 ng*h/mL | Geometric Coefficient of Variation 12 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 21 - Stage 1B All Cohorts | 13500 ng*h/mL | Geometric Coefficient of Variation 39 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 21 - Stage 1B All Cohorts | NA ng*h/mL | — |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 21 - Stage 1B All Cohorts | 5410 ng*h/mL | Geometric Coefficient of Variation 57 |
Secondary
AUC0-24 of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts
Stage 2 PK data were reported for each indication specific cohort separately.
Time frame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | 3390 ng*h/mL | Geometric Coefficient of Variation 39 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | 5250 ng*h/mL | Geometric Coefficient of Variation 66 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | 4580 ng*h/mL | Geometric Coefficient of Variation 56 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | AUC0-24 of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | NA ng*h/mL | — |
Secondary
CL/F of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Time frame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | CL/F of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | 7.49 L/hr | Geometric Coefficient of Variation 18 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | CL/F of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | 17.6 L/hr | Geometric Coefficient of Variation 55 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | CL/F of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | 12.5 L/hr | Geometric Coefficient of Variation 28 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | CL/F of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | 40.9 L/hr | Geometric Coefficient of Variation 50 |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | CL/F of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | 17.9 L/hr | Geometric Coefficient of Variation 55 |
| S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib | CL/F of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | 19.4 L/hr | Geometric Coefficient of Variation 69 |
| S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib | CL/F of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | 13.6 L/hr | Geometric Coefficient of Variation 23 |
Secondary
CL/F of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts
Stage 2A PK data were reported for each indication specific cohort separately. Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. As planned, summary statistics were not derived if fewer than 3 participants had available data; however, if the number of participants analyzed = 1, then the observed data of the single participant was reported as geometric mean.
Time frame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | CL/F of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 13.1 L/hr | — |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | CL/F of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 15.8 L/hr | Geometric Coefficient of Variation 16 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | CL/F of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 16.9 L/hr | Geometric Coefficient of Variation 32 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | CL/F of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 21.6 L/hr | Geometric Coefficient of Variation 46 |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | CL/F of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | NA L/hr | — |
Secondary
CL/F of Cobimetinib on Cycle 1 Day 21 - Stage 1B All Cohorts
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Time frame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | CL/F of Cobimetinib on Cycle 1 Day 21 - Stage 1B All Cohorts | 12.2 L/hr | Geometric Coefficient of Variation 64 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | CL/F of Cobimetinib on Cycle 1 Day 21 - Stage 1B All Cohorts | 9.26 L/hr | Geometric Coefficient of Variation 150 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | CL/F of Cobimetinib on Cycle 1 Day 21 - Stage 1B All Cohorts | NA L/hr | — |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | CL/F of Cobimetinib on Cycle 1 Day 21 - Stage 1B All Cohorts | 14.3 L/hr | Geometric Coefficient of Variation 52 |
Secondary
CL/F of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts
Stage 2 PK data were reported for each indication specific cohort separately. Half-life is the time measured for the plasma concentration to decrease by one half. Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Time frame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22, Cycle 2 Days 1, 15, 21
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | CL/F of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | 18.2 L/hr | Geometric Coefficient of Variation 57 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | CL/F of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | 8.76 L/hr | Geometric Coefficient of Variation 68 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | CL/F of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | 8.52 L/hr | Geometric Coefficient of Variation 120 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | CL/F of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | NA L/hr | — |
Secondary
CL/F of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Time frame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | CL/F of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | 11.5 L/hr | Geometric Coefficient of Variation 21 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | CL/F of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | 23.5 L/hr | Geometric Coefficient of Variation 88 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | CL/F of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | 18.6 L/hr | Geometric Coefficient of Variation 38 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | CL/F of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | 29.4 L/hr | Geometric Coefficient of Variation 110 |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | CL/F of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | 20.3 L/hr | Geometric Coefficient of Variation 58 |
| S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib | CL/F of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | 22.1 L/hr | Geometric Coefficient of Variation 58 |
| S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib | CL/F of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | 24.2 L/hr | Geometric Coefficient of Variation 44 |
Secondary
CL/F of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts
Stage 2A PK data were reported for each indication specific cohort separately. Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. As planned, summary statistics were not derived if fewer than 3 participants had available data; however, if the number of participants analyzed = 1, then the observed data of the single participant was reported as geometric mean.
Time frame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | CL/F of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 28.6 L/hr | — |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | CL/F of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 28.5 L/hr | Geometric Coefficient of Variation 31 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | CL/F of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 30.3 L/hr | Geometric Coefficient of Variation 73 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | CL/F of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 45.1 L/hr | Geometric Coefficient of Variation 74 |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | CL/F of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | NA L/hr | — |
Secondary
CL/F of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Time frame: Cohorts 1-3: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 28, Cycle 1 Day 29, Cycle 2 Days 1, 15, 21; Cohorts 4-6A: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22, Cycle 2 Days 1, 15, 21
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | CL/F of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 32.0 L/hr | Geometric Coefficient of Variation 21 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | CL/F of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 34.1 L/hr | Geometric Coefficient of Variation 150 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | CL/F of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 14.5 L/hr | Geometric Coefficient of Variation 34 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | CL/F of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 25.7 L/hr | Geometric Coefficient of Variation 63 |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | CL/F of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 30.1 L/hr | Geometric Coefficient of Variation 58 |
| S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib | CL/F of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 22.2 L/hr | Geometric Coefficient of Variation 40 |
| S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib | CL/F of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 24.6 L/hr | — |
Secondary
CL/F of Pictilisib on Cycle 1 Day 21 - Stage 1B All Cohorts
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Time frame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | CL/F of Pictilisib on Cycle 1 Day 21 - Stage 1B All Cohorts | 18.6 L/hr | Geometric Coefficient of Variation 12 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | CL/F of Pictilisib on Cycle 1 Day 21 - Stage 1B All Cohorts | 13.3 L/hr | Geometric Coefficient of Variation 39 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | CL/F of Pictilisib on Cycle 1 Day 21 - Stage 1B All Cohorts | NA L/hr | — |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | CL/F of Pictilisib on Cycle 1 Day 21 - Stage 1B All Cohorts | 33.3 L/hr | Geometric Coefficient of Variation 57 |
Secondary
CL/F of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts
Stage 2 PK data were reported for each indication specific cohort separately. Half-life is the time measured for the plasma concentration to decrease by one half. Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Time frame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22, Cycle 2 Days 1, 15, 21
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | CL/F of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | 29.5 L/hr | Geometric Coefficient of Variation 39 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | CL/F of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | 19.1 L/hr | Geometric Coefficient of Variation 66 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | CL/F of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | 21.8 L/hr | Geometric Coefficient of Variation 56 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | CL/F of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | NA L/hr | — |
Secondary
Cmax of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts
Time frame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | 802 ng/mL | Geometric Coefficient of Variation 24 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | 372 ng/mL | Geometric Coefficient of Variation 45 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | 616 ng/mL | Geometric Coefficient of Variation 39 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | 204 ng/mL | Geometric Coefficient of Variation 57 |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | 409 ng/mL | Geometric Coefficient of Variation 43 |
| S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | 475 ng/mL | Geometric Coefficient of Variation 86 |
| S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | 682 ng/mL | Geometric Coefficient of Variation 23 |
Secondary
Cmax of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts
Stage 2A PK data were reported for each indication specific cohort separately. As planned, summary statistics were not derived if fewer than 3 participants had available data; however, if the number of participants analyzed = 1, then the observed data of the single participant was reported as geometric mean.
Time frame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 587 ng/mL | — |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 502 ng/mL | Geometric Coefficient of Variation 16 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 469 ng/mL | Geometric Coefficient of Variation 40 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 393 ng/mL | Geometric Coefficient of Variation 44 |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | NA ng/mL | — |
Secondary
Cmax of Cobimetinib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts
Time frame: Cohorts 1-3: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 8, Cycle 1 Days 9, 15, 21; Cohorts 4-6A: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Day 2, 8, 14
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | 20.2 ng/mL | Geometric Coefficient of Variation 100 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | 17.7 ng/mL | Geometric Coefficient of Variation 62 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | 87.4 ng/mL | Geometric Coefficient of Variation 73 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | 101 ng/mL | Geometric Coefficient of Variation 63 |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | 61.0 ng/mL | Geometric Coefficient of Variation 45 |
| S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | 131 ng/mL | Geometric Coefficient of Variation 66 |
| S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | 138 ng/mL | Geometric Coefficient of Variation 61 |
Secondary
Cmax of Cobimetinib on Cycle 1 Day 1 - Stage 1A All Cohorts
Time frame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 15-17
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 1 - Stage 1A All Cohorts | 301 ng/mL | Geometric Coefficient of Variation 87 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 1 - Stage 1A All Cohorts | 137 ng/mL | Geometric Coefficient of Variation 66 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 1 - Stage 1A All Cohorts | 436 ng/mL | Geometric Coefficient of Variation 67 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 1 - Stage 1A All Cohorts | 184 ng/mL | Geometric Coefficient of Variation 47 |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 1 - Stage 1A All Cohorts | 275 ng/mL | Geometric Coefficient of Variation 72 |
| S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 1 - Stage 1A All Cohorts | 333 ng/mL | Geometric Coefficient of Variation 45 |
| S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 1 - Stage 1A All Cohorts | 311 ng/mL | Geometric Coefficient of Variation 48 |
Secondary
Cmax of Cobimetinib on Cycle 1 Day 1 - Stage 1B All Cohorts
Time frame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Day 2
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 1 - Stage 1B All Cohorts | 55 ng/mL | Geometric Coefficient of Variation 160 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 1 - Stage 1B All Cohorts | 123 ng/mL | Geometric Coefficient of Variation 56 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 1 - Stage 1B All Cohorts | 45.6 ng/mL | Geometric Coefficient of Variation 110 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 1 - Stage 1B All Cohorts | 77.8 ng/mL | Geometric Coefficient of Variation 110 |
Secondary
Cmax of Cobimetinib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts
Stage 2A PK data were reported for each indication specific cohort separately.
Time frame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 15-17
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts | 487 ng/mL | — |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts | 334 ng/mL | Geometric Coefficient of Variation 44 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts | 256 ng/mL | Geometric Coefficient of Variation 130 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts | 277 ng/mL | Geometric Coefficient of Variation 110 |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts | 408 ng/mL | Geometric Coefficient of Variation 89 |
Secondary
Cmax of Cobimetinib on Cycle 1 Day 1 - Stage 2 Individual Indication Specific Cohorts
Stage 2 PK data were reported for each indication specific cohort separately.
Time frame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 14
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 1 - Stage 2 Individual Indication Specific Cohorts | 73.8 ng/mL | Geometric Coefficient of Variation 38 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 1 - Stage 2 Individual Indication Specific Cohorts | 90.7 ng/mL | Geometric Coefficient of Variation 87 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 1 - Stage 2 Individual Indication Specific Cohorts | 116 ng/mL | Geometric Coefficient of Variation 63 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 1 - Stage 2 Individual Indication Specific Cohorts | 48.2 ng/mL | Geometric Coefficient of Variation 97 |
Secondary
Cmax of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts
Time frame: Cohorts 1-3: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 28, Cycle 1 Day 29, Cycle 2 Days 1, 15, 21; Cohorts 4-6A: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22, Cycle 2 Days 1, 15, 21
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 37.1 ng/mL | Geometric Coefficient of Variation 5.6 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 52.2 ng/mL | Geometric Coefficient of Variation 57 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 228 ng/mL | Geometric Coefficient of Variation 120 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 167 ng/mL | Geometric Coefficient of Variation 56 |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 138 ng/mL | Geometric Coefficient of Variation 63 |
| S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 245 ng/mL | Geometric Coefficient of Variation 79 |
| S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 87.4 ng/mL | — |
Secondary
Cmax of Cobimetinib on Cycle 1 Day 21 - Stage 1B All Cohorts
Time frame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 21 - Stage 1B All Cohorts | 174 ng/mL | Geometric Coefficient of Variation 50 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 21 - Stage 1B All Cohorts | 232 ng/mL | Geometric Coefficient of Variation 120 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 21 - Stage 1B All Cohorts | 158 ng/mL | Geometric Coefficient of Variation 73 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 21 - Stage 1B All Cohorts | 245 ng/mL | Geometric Coefficient of Variation 45 |
Secondary
Cmax of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts
Stage 2 PK data were reported for each indication specific cohort separately.
Time frame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22, Cycle 2 Days 1, 15, 21
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | 119 ng/mL | Geometric Coefficient of Variation 62 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | 237 ng/mL | Geometric Coefficient of Variation 63 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | 254 ng/mL | Geometric Coefficient of Variation 120 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Cmax of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | NA ng/mL | — |
Secondary
Cmax of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts
Time frame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | 809 ng/mL | Geometric Coefficient of Variation 41 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | 709 ng/mL | Geometric Coefficient of Variation 71 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | 597 ng/mL | Geometric Coefficient of Variation 38 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | 579 ng/mL | Geometric Coefficient of Variation 100 |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | 833 ng/mL | Geometric Coefficient of Variation 49 |
| S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | 743 ng/mL | Geometric Coefficient of Variation 53 |
| S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | 646 ng/mL | Geometric Coefficient of Variation 24 |
Secondary
Cmax of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts
Stage 2A PK data were reported for each indication specific cohort separately. As planned, summary statistics were not derived if fewer than 3 participants had available data; however, if the number of participants analyzed = 1, then the observed data of the single participant was reported as geometric mean.
Time frame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 412 ng/mL | — |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 518 ng/mL | Geometric Coefficient of Variation 67 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 520 ng/mL | Geometric Coefficient of Variation 84 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 334 ng/mL | Geometric Coefficient of Variation 83 |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | NA ng/mL | — |
Secondary
Cmax of Pictilisib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts
Time frame: Cohorts 1-3: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 8, Cycle 1 Day 9, 15, 21; Cohorts 4-6A: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Day 2, 8, 14
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | 196 ng/mL | Geometric Coefficient of Variation 20 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | 193 ng/mL | Geometric Coefficient of Variation 16 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | 329 ng/mL | Geometric Coefficient of Variation 26 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | 390 ng/mL | Geometric Coefficient of Variation 60 |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | 302 ng/mL | Geometric Coefficient of Variation 34 |
| S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | 272 ng/mL | Geometric Coefficient of Variation 54 |
| S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | 355 ng/mL | Geometric Coefficient of Variation 83 |
Secondary
Cmax of Pictilisib on Cycle 1 Day 1 - Stage 1A All Cohorts
Time frame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 15-17
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 1 - Stage 1A All Cohorts | 547 ng/mL | Geometric Coefficient of Variation 80 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 1 - Stage 1A All Cohorts | 408 ng/mL | Geometric Coefficient of Variation 190 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 1 - Stage 1A All Cohorts | 390 ng/mL | Geometric Coefficient of Variation 76 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 1 - Stage 1A All Cohorts | 367 ng/mL | Geometric Coefficient of Variation 61 |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 1 - Stage 1A All Cohorts | 832 ng/mL | Geometric Coefficient of Variation 35 |
| S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 1 - Stage 1A All Cohorts | 619 ng/mL | Geometric Coefficient of Variation 110 |
| S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 1 - Stage 1A All Cohorts | 514 ng/mL | Geometric Coefficient of Variation 81 |
Secondary
Cmax of Pictilisib on Cycle 1 Day 1 - Stage 1B All Cohorts
Time frame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Day 2
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 1 - Stage 1B All Cohorts | 527 ng/mL | Geometric Coefficient of Variation 67 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 1 - Stage 1B All Cohorts | 609 ng/mL | Geometric Coefficient of Variation 27 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 1 - Stage 1B All Cohorts | 168 ng/mL | Geometric Coefficient of Variation 130 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 1 - Stage 1B All Cohorts | 363 ng/mL | Geometric Coefficient of Variation 64 |
Secondary
Cmax of Pictilisib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts
Stage 2A PK data were reported for each indication specific cohort separately.
Time frame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 15-17
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts | 714 ng/mL | — |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts | 265 ng/mL | Geometric Coefficient of Variation 140 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts | 289 ng/mL | Geometric Coefficient of Variation 100 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts | 393 ng/mL | Geometric Coefficient of Variation 90 |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts | 369 ng/mL | Geometric Coefficient of Variation 35 |
Secondary
Cmax of Pictilisib on Cycle 1 Day 1 - Stage 2 Individual Indication Specific Cohorts
Stage 2 PK data were reported for each indication specific cohort separately.
Time frame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 14
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 1 - Stage 2 Individual Indication Specific Cohorts | 298 ng/mL | Geometric Coefficient of Variation 52 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 1 - Stage 2 Individual Indication Specific Cohorts | 355 ng/mL | Geometric Coefficient of Variation 55 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 1 - Stage 2 Individual Indication Specific Cohorts | 315 ng/mL | Geometric Coefficient of Variation 58 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 1 - Stage 2 Individual Indication Specific Cohorts | 253 ng/mL | Geometric Coefficient of Variation 90 |
Secondary
Cmax of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts
Time frame: Cohorts 1-3: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 28, Cycle 1 Day 29, Cycle 2 Days 1, 15, 21; Cohorts 4-6A: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22, Cycle 2 Days 1, 15, 21
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 198 ng/mL | Geometric Coefficient of Variation 38 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 278 ng/mL | Geometric Coefficient of Variation 100 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 459 ng/mL | Geometric Coefficient of Variation 20 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 409 ng/mL | Geometric Coefficient of Variation 49 |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 374 ng/mL | Geometric Coefficient of Variation 69 |
| S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 396 ng/mL | Geometric Coefficient of Variation 48 |
| S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 441 ng/mL | — |
Secondary
Cmax of Pictilisib on Cycle 1 Day 21 - Stage 1B All Cohorts
Time frame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 21 - Stage 1B All Cohorts | 508 ng/mL | Geometric Coefficient of Variation 10 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 21 - Stage 1B All Cohorts | 1010 ng/mL | Geometric Coefficient of Variation 27 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 21 - Stage 1B All Cohorts | 227 ng/mL | Geometric Coefficient of Variation 19 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 21 - Stage 1B All Cohorts | 408 ng/mL | Geometric Coefficient of Variation 62 |
Secondary
Cmax of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts
Stage 2 PK data were reported for each indication specific cohort separately.
Time frame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22, Cycle 2 Days 1, 15, 21
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | 231 ng/mL | Geometric Coefficient of Variation 63 |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | 362 ng/mL | Geometric Coefficient of Variation 60 |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | 369 ng/mL | Geometric Coefficient of Variation 66 |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Cmax of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | NA ng/mL | — |
Secondary
Duration of Objective Response - Dose Escalation Stages 1, 1A and 1B
Duration of objective response was defined as the time from first occurrence of a documented objective response (CR or PR) until the time of disease progression, as determined by investigator review of tumor assessments using RECIST, or death from any cause during the study (within 30 days after the last dose of study treatment). CR = disappearance of all target and non-target lesions. PR = at least 30 % decrease in sum of the longest diameter of measured lesions taking as reference the baseline sum of the longest diameter. PD = at least 20% increase in the sum of the longest diameter of measured lesions taking as reference the smallest sum of the longest diameter since treatment start or appearance of one or more new lesions.
Time frame: Up to 30 days after last dose (last dose = up to Cycle 15, cycle length = 28 days)
Population: Data for this outcome measure was not collected as per changes in planned analysis.
Secondary
Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B
Tumor response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) = disappearance of all target and non-target lesions. Partial Response (PR) = at least 30 percent (%) decrease in sum of the longest diameter of measured lesions taking as reference the baseline sum of the longest diameter. Progressive disease (PD) = at least 20% increase in the sum of the longest diameter of measured lesions taking as reference the smallest sum of the longest diameter since treatment start or appearance of one or more new lesions. Stable disease (SD) = neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of the longest diameter since treatment start.
Time frame: Up to 30 days after last dose (last dose = up to Cycle 15, cycle length = 28 days)
Population: Safety-evaluable population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | Unable to Evaluate | 0 participants |
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | SD | 2 participants |
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | PD | 0 participants |
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | PR | 0 participants |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | SD | 2 participants |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | PR | 0 participants |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | Unable to Evaluate | 0 participants |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | PD | 1 participants |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | Unable to Evaluate | 0 participants |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | PR | 0 participants |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | PD | 2 participants |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | SD | 1 participants |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | SD | 15 participants |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | PR | 0 participants |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | PD | 16 participants |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | Unable to Evaluate | 0 participants |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | Unable to Evaluate | 0 participants |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | PR | 0 participants |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | SD | 5 participants |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | PD | 5 participants |
| S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | Unable to Evaluate | 0 participants |
| S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | PR | 1 participants |
| S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | PD | 4 participants |
| S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | SD | 3 participants |
| S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | SD | 1 participants |
| S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | PD | 0 participants |
| S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | PR | 0 participants |
| S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | Unable to Evaluate | 0 participants |
| S1A CA: 100 mg Cobimetinib + 130 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | PR | 0 participants |
| S1A CA: 100 mg Cobimetinib + 130 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | PD | 2 participants |
| S1A CA: 100 mg Cobimetinib + 130 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | Unable to Evaluate | 0 participants |
| S1A CA: 100 mg Cobimetinib + 130 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | SD | 0 participants |
| S1A CB: 100 mg Cobimetinib + 180 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | Unable to Evaluate | 0 participants |
| S1A CB: 100 mg Cobimetinib + 180 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | PR | 0 participants |
| S1A CB: 100 mg Cobimetinib + 180 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | PD | 1 participants |
| S1A CB: 100 mg Cobimetinib + 180 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | SD | 2 participants |
| S1A CC: 125 mg Cobimetinib + 130 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | PR | 1 participants |
| S1A CC: 125 mg Cobimetinib + 130 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | Unable to Evaluate | 0 participants |
| S1A CC: 125 mg Cobimetinib + 130 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | SD | 3 participants |
| S1A CC: 125 mg Cobimetinib + 130 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | PD | 0 participants |
| S1A CD: 125 mg Cobimetinib + 180 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | SD | 16 participants |
| S1A CD: 125 mg Cobimetinib + 180 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | PR | 2 participants |
| S1A CD: 125 mg Cobimetinib + 180 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | PD | 17 participants |
| S1A CD: 125 mg Cobimetinib + 180 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | Unable to Evaluate | 0 participants |
| S1A CE: 125 mg Cobimetinib + 245 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | Unable to Evaluate | 1 participants |
| S1A CE: 125 mg Cobimetinib + 245 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | SD | 5 participants |
| S1A CE: 125 mg Cobimetinib + 245 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | PD | 1 participants |
| S1A CE: 125 mg Cobimetinib + 245 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | PR | 0 participants |
| S1A CF: 150 mg Cobimetinib + 180 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | PR | 0 participants |
| S1A CF: 150 mg Cobimetinib + 180 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | PD | 4 participants |
| S1A CF: 150 mg Cobimetinib + 180 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | Unable to Evaluate | 0 participants |
| S1A CF: 150 mg Cobimetinib + 180 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | SD | 2 participants |
| S1A CG: 150 mg Cobimetinib + 245 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | Unable to Evaluate | 0 participants |
| S1A CG: 150 mg Cobimetinib + 245 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | SD | 0 participants |
| S1A CG: 150 mg Cobimetinib + 245 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | PR | 0 participants |
| S1A CG: 150 mg Cobimetinib + 245 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | PD | 3 participants |
| S1B CAX: 40 mg Cobimetinib + 130 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | Unable to Evaluate | 0 participants |
| S1B CAX: 40 mg Cobimetinib + 130 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | SD | 1 participants |
| S1B CAX: 40 mg Cobimetinib + 130 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | PD | 3 participants |
| S1B CAX: 40 mg Cobimetinib + 130 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | PR | 0 participants |
| S1B CBX: 40 mg Cobimetinib + 180 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | PD | 2 participants |
| S1B CBX: 40 mg Cobimetinib + 180 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | PR | 0 participants |
| S1B CBX: 40 mg Cobimetinib + 180 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | Unable to Evaluate | 0 participants |
| S1B CBX: 40 mg Cobimetinib + 180 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | SD | 1 participants |
| S1B CCX: 60 mg Cobimetinib + 130 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | PD | 3 participants |
| S1B CCX: 60 mg Cobimetinib + 130 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | SD | 0 participants |
| S1B CCX: 60 mg Cobimetinib + 130 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | PR | 0 participants |
| S1B CCX: 60 mg Cobimetinib + 130 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | Unable to Evaluate | 0 participants |
| S1B CDX: 60 mg Cobimetinib + 180 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | Unable to Evaluate | 0 participants |
| S1B CDX: 60 mg Cobimetinib + 180 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | SD | 1 participants |
| S1B CDX: 60 mg Cobimetinib + 180 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | PR | 0 participants |
| S1B CDX: 60 mg Cobimetinib + 180 mg Pictilisib | Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B | PD | 2 participants |
Secondary
Progression-Free Survival (PFS) - Dose Escalation Stages 1, 1A and 1B
PFS was the time from study treatment initiation to the first occurrence of disease progression, as determined by investigator review of tumor assessments using RECIST, or death from any cause during the study (within 30 days after the last dose of study treatment). PD = at least 20% increase in the sum of the longest diameter of measured lesions taking as reference the smallest sum of the longest diameter since treatment start or appearance of one or more new lesions.
Time frame: Up to 30 days after last dose (last dose = up to Cycle 15, cycle length = 28 days)
Population: Data for this outcome measure was not collected as per changes in planned analysis.
Secondary
t1/2 of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts
Half-life is the time measured for the plasma concentration to decrease by one half.
Time frame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | t1/2 of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | NA hours |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | t1/2 of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | 46.1 hours |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | t1/2 of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | 47.4 hours |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | t1/2 of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | 48.8 hours |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | t1/2 of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | 48 hours |
| S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib | t1/2 of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | NA hours |
| S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib | t1/2 of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | 46.2 hours |
Secondary
t1/2 of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts
Stage 2A PK data were reported for each indication specific cohort separately. Half-life is the time measured for the plasma concentration to decrease by one half. As planned, summary statistics were not derived if fewer than 3 participants had available data; however, if the number of participants analyzed = 1, then the observed data of the single participant was reported as geometric mean.
Time frame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | t1/2 of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 37.7 hours |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | t1/2 of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 38.6 hours |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | t1/2 of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 50.2 hours |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | t1/2 of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 42.6 hours |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | t1/2 of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | NA hours |
Secondary
t1/2 of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts
Stage 2 PK data were reported for each indication specific cohort separately. Half-life is the time measured for the plasma concentration to decrease by one half.
Time frame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | t1/2 of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | 42.5 hours |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | t1/2 of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | 51.5 hours |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | t1/2 of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | 36.0 hours |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | t1/2 of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | NA hours |
Secondary
t1/2 of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts
Half-life is the time measured for the plasma concentration to decrease by one half. As planned, summary statistics were not derived if fewer than 3 participants had available data; however, if the number of participants analyzed = 1, then the observed data of the single participant was reported as geometric mean.
Time frame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | t1/2 of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | NA hours |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | t1/2 of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | NA hours |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | t1/2 of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | 34.9 hours |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | t1/2 of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | 36.5 hours |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | t1/2 of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | 38.4 hours |
| S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib | t1/2 of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | NA hours |
| S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib | t1/2 of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | NA hours |
Secondary
t1/2 of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts
Stage 2A PK data were reported for each indication specific cohort separately. Half-life is the time measured for the plasma concentration to decrease by one half.
Time frame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | t1/2 of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 44.6 hours |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | t1/2 of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 58.2 hours |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | t1/2 of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 37.8 hours |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | t1/2 of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 30.3 hours |
Secondary
t1/2 of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts
Half-life is the time measured for the plasma concentration to decrease by one half. As planned, summary statistics were not derived if fewer than 3 participants had available data; however, if the number of participants analyzed = 1, then the observed data of the single participant was reported as geometric mean.
Time frame: Cohorts 1-3: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 28, Cycle 1 Day 29, Cycle 2 Days 1, 15, 21; Cohorts 4-6A: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22, Cycle 2 Days 1, 15, 21
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | t1/2 of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 25.8 hours |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | t1/2 of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | NA hours |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | t1/2 of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 24.7 hours |
| S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib | t1/2 of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 27.7 hours |
Secondary
t1/2 of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts
Stage 2 PK data were reported for each indication specific cohort separately. Half-life is the time measured for the plasma concentration to decrease by one half.
Time frame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22, Cycle 2 Days 1, 15, 21
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | t1/2 of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | 183 hours |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | t1/2 of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | 28.5 hours |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | t1/2 of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | 26.6 hours |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | t1/2 of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | 30.9 hours |
Secondary
Terminal Half-life (t1/2) of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts
Half-life is the time measured for the plasma concentration to decrease by one half.
Time frame: Cohorts 1-3: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 28, Cycle 1 Day 29, Cycle 2 Days 1, 15, 21; Cohorts 4-6A: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22, Cycle 2 Days 1, 15, 21
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Terminal Half-life (t1/2) of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 49.3 hours |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Terminal Half-life (t1/2) of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 37.9 hours |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Terminal Half-life (t1/2) of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 31.7 hours |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Terminal Half-life (t1/2) of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 34.1 hours |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | Terminal Half-life (t1/2) of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 43.2 hours |
| S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib | Terminal Half-life (t1/2) of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 45.7 hours |
| S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib | Terminal Half-life (t1/2) of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 40.5 hours |
Secondary
Tmax of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts
Time frame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | 2.00 hours |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | 2.00 hours |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | 2.00 hours |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | 4.00 hours |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | 4.00 hours |
| S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | 5.00 hours |
| S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts | 3.00 hours |
Secondary
Tmax of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts
Stage 2A PK data were reported for each indication specific cohort separately. As planned, summary statistics were not derived if fewer than 3 participants had available data; however, if the number of participants analyzed = 1, then the observed data of the single participant was reported as median.
Time frame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 4.00 hours |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 4.00 hours |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 3.00 hours |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 4.00 hours |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | NA hours |
Secondary
Tmax of Cobimetinib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts
Time frame: Cohorts 1-3: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 8, Cycle 1 Days 9, 15, 21; Cohorts 4-6A: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Day 2, 8, 14
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | 4.00 hours |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | 4.00 hours |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | 2.00 hours |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | 2.00 hours |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | 2.00 hours |
| S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | 4.00 hours |
| S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | 3.00 hours |
Secondary
Tmax of Cobimetinib on Cycle 1 Day 1 - Stage 1A All Cohorts
Time frame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 15-17
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 1 - Stage 1A All Cohorts | 2.00 hours |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 1 - Stage 1A All Cohorts | 4.00 hours |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 1 - Stage 1A All Cohorts | 2.00 hours |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 1 - Stage 1A All Cohorts | 4.00 hours |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 1 - Stage 1A All Cohorts | 4.00 hours |
| S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 1 - Stage 1A All Cohorts | 5.00 hours |
| S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 1 - Stage 1A All Cohorts | 4.00 hours |
Secondary
Tmax of Cobimetinib on Cycle 1 Day 1 - Stage 1B All Cohorts
Time frame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Day 2
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 1 - Stage 1B All Cohorts | 3.00 hours |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 1 - Stage 1B All Cohorts | 2.00 hours |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 1 - Stage 1B All Cohorts | 4.00 hours |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 1 - Stage 1B All Cohorts | 4.00 hours |
Secondary
Tmax of Cobimetinib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts
Stage 2A PK data were reported for each indication specific cohort separately.
Time frame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 15-17
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts | 4.00 hours |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts | 6.00 hours |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts | 4.00 hours |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts | 4.00 hours |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts | 2.00 hours |
Secondary
Tmax of Cobimetinib on Cycle 1 Day 1 - Stage 2 Individual Indication Specific Cohorts
Stage 2 PK data were reported for each indication specific cohort separately.
Time frame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 14
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 1 - Stage 2 Individual Indication Specific Cohorts | 2.00 hours |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 1 - Stage 2 Individual Indication Specific Cohorts | 4.00 hours |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 1 - Stage 2 Individual Indication Specific Cohorts | 3.00 hours |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 1 - Stage 2 Individual Indication Specific Cohorts | 4.00 hours |
Secondary
Tmax of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts
Time frame: Cohorts 1-3: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 28, Cycle 1 Day 29, Cycle 2 Days 1, 15, 21; Cohorts 4-6A: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22, Cycle 2 Days 1, 15, 21
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 6.00 hours |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 4.00 hours |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 2.00 hours |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 2.00 hours |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 4.00 hours |
| S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 3.0 hours |
| S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 4 hours |
Secondary
Tmax of Cobimetinib on Cycle 1 Day 21 - Stage 1B All Cohorts
Time frame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 21 - Stage 1B All Cohorts | 5.00 hours |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 21 - Stage 1B All Cohorts | 4.00 hours |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 21 - Stage 1B All Cohorts | 2.00 hours |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 21 - Stage 1B All Cohorts | 6.00 hours |
Secondary
Tmax of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts
Stage 2 PK data were reported for each indication specific cohort separately.
Time frame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22, Cycle 2 Days 1, 15, 21
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | 4.00 hours |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | 4.00 hours |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | 2.00 hours |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Tmax of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | NA hours |
Secondary
Tmax of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts
Time frame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | 2.00 hours |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | 2.00 hours |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | 2.00 hours |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | 2.00 hours |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | 3.00 hours |
| S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | 2.00 hours |
| S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts | 3.00 hours |
Secondary
Tmax of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts
Stage 2A PK data were reported for each indication specific cohort separately. As planned, summary statistics were not derived if fewer than 3 participants had available data; however, if the number of participants analyzed = 1, then the observed data of the single participant was reported as geometric mean.
Time frame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 18, Cycle 1 Day 19, Cycle 2 Days 1, 15, 21
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 2.00 hours |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 2.00 hours |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 2.00 hours |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | 2.00 hours |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 18 - Stage 2A Individual Indication Specific Cohorts | NA hours |
Secondary
Tmax of Pictilisib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts
Time frame: Cohorts 1-3: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 8, Cycle 1 Day 9, 15, 21; Cohorts 4-6A: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Day 2, 8, 14
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | 2.00 hours |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | 2.00 hours |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | 2.00 hours |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | 2.00 hours |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | 2.00 hours |
| S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | 2.00 hours |
| S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts | 2.00 hours |
Secondary
Tmax of Pictilisib on Cycle 1 Day 1 - Stage 1A All Cohorts
Time frame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 15-17
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 1 - Stage 1A All Cohorts | 2.00 hours |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 1 - Stage 1A All Cohorts | 2.00 hours |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 1 - Stage 1A All Cohorts | 2.00 hours |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 1 - Stage 1A All Cohorts | 2.00 hours |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 1 - Stage 1A All Cohorts | 2.00 hours |
| S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 1 - Stage 1A All Cohorts | 2.00 hours |
| S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 1 - Stage 1A All Cohorts | 4.00 hours |
Secondary
Tmax of Pictilisib on Cycle 1 Day 1 - Stage 1B All Cohorts
Time frame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Day 2
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 1 - Stage 1B All Cohorts | 2.00 hours |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 1 - Stage 1B All Cohorts | 2.00 hours |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 1 - Stage 1B All Cohorts | 2.00 hours |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 1 - Stage 1B All Cohorts | 4.00 hours |
Secondary
Tmax of Pictilisib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts
Stage 2A PK data were reported for each indication specific cohort separately.
Time frame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 15-17
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts | 2.00 hours |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts | 2.00 hours |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts | 2.00 hours |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts | 2.00 hours |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 1 - Stage 2A Individual Indication Specific Cohorts | 4.00 hours |
Secondary
Tmax of Pictilisib on Cycle 1 Day 1 - Stage 2 Individual Indication Specific Cohorts
Stage 2 PK data were reported for each indication specific cohort separately.
Time frame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 14
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 1 - Stage 2 Individual Indication Specific Cohorts | 2.00 hours |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 1 - Stage 2 Individual Indication Specific Cohorts | 2.00 hours |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 1 - Stage 2 Individual Indication Specific Cohorts | 2.00 hours |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 1 - Stage 2 Individual Indication Specific Cohorts | 4.00 hours |
Secondary
Tmax of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts
Time frame: Cohorts 1-3: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 28, Cycle 1 Day 29, Cycle 2 Days 1, 15, 21; Cohorts 4-6A: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22, Cycle 2 Days 1, 15, 21
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 2.00 hours |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 2.00 hours |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 2.00 hours |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 2.00 hours |
| S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 2.00 hours |
| S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 2.00 hours |
| S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts | 2.00 hours |
Secondary
Tmax of Pictilisib on Cycle 1 Day 21 - Stage 1B All Cohorts
Time frame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 21 - Stage 1B All Cohorts | 4.00 hours |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 21 - Stage 1B All Cohorts | 2.00 hours |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 21 - Stage 1B All Cohorts | 4.00 hours |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 21 - Stage 1B All Cohorts | 5.00 hours |
Secondary
Tmax of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts
Stage 2 PK data were reported for each indication specific cohort separately.
Time frame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22, Cycle 2 Days 1, 15, 21
Population: PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | 4.00 hours |
| S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | 2.00 hours |
| S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | 2.00 hours |
| S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib | Tmax of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts | NA hours |