All Drugs and Chemicals

Mitogens

Participants will receive cobimetinib capsules (at a starting dose of 20 milligrams \[mg\]) and pictilisib capsules (at a starting dose of 80 mg) from Days 1 to 21 and then 7 days off study drugs from Days 22 to 28 in continuous 28-day cycles. Doses will be increased to identify maximum tolerated dose (MTD) or potential recommended Phase 2 dose (RP2D). Treatment will continue until disease progression, unacceptable toxicity, or any other discontinuation criterion meets.

Participants will receive cobimetinib capsules (at a starting dose of 100 mg) on Days 1, 4, 8, 11, 15, and 18 and pictilisib capsules (at a starting dose of 130 mg) from Days 1 to 21 and then 7 days off study drugs from Days 22 to 28 in continuous 28-day cycles. Doses will be increased to identify MTD or potential RP2D.Treatment will continue until disease progression, unacceptable toxicity, or any other discontinuation criterion meets.

Participants will receive cobimetinib capsules (at a starting dose of 40 mg) and pictilisib capsules (at a starting dose of 130 mg) from Days 1 to 7 and then from Days 15 to 21 in continuous 28-day cycles. Participants will be off study drugs from Days 8 to 14 and from Days 22 to 28. Treatment will continue until disease progression, unacceptable toxicity, or any other discontinuation criterion meets.

Participants will received cobimetinib capsules and pictilisib capsules from Days 1 to 21 and then 7 days off study drugs from Days 22 to 28 in continuous 28-day cycles, at doses identified as MTD/potential RP2D from Stage 1. Treatment will continue until disease progression, unacceptable toxicity, or any other discontinuation criterion meets. This indication specific cohort will include participants with Kirsten rat sarcoma viral oncogene homolog (KRAS) mutant non-small cell lung cancer (NSCLC); epidermal growth factor receptor (EGFR) T790M mutant and EGFR inhibitor-progressing NSCLC; pancreatic adenocarcinoma; and KRAS mutant colorectal cancer (CRC).

Participants received cobimetinib capsules on Days 1, 4, 8, 11, 15, and 18 and pictilisib capsules from Days 1 to 21 and then 7 days off study drugs from Days 22 to 28 in continuous 28-day cycles, at doses identified as MTD/potential RP2D from Stage 1A. Treatment will continue until disease progression, unacceptable toxicity, or any other discontinuation criterion meets. This indication specific cohort will include participants with KRAS mutant NSCLC; EGFR T790M mutant and EGFR inhibitor-progressing NSCLC; pancreatic adenocarcinoma; KRAS mutant CRC, and KRAS mutant endometrioid carcinoma.

Participants will receive cobimetinib capsules and pictilisib capsules from Days 1 to 7 and then from Days 15 to 21 in continuous 28-day cycles, at doses identified as MTD/potential RP2D from Stage 1B. Participants will be off study drugs from Days 8 to 14 and from Days 22 to 28. Treatment will continue until disease progression, unacceptable toxicity, or any other discontinuation criterion meets. This indication specific cohort will include participants with KRAS mutant endometrioid carcinoma.

Cobimetinib

Pictilisib

Iris Chan, M.D., Ph.D.

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.

Safety, Tolerability and Pharmacokinetics of Cobimetinib in Combination With Pictilisib in Patients With Locally Advanced or Metastatic Solid Tumors

A Phase Ib, Open-Label, Dose-Escalation Study Evaluating the Safety, Tolerability and Pharmacokinetics of GDC-0973 in Combination With GDC-0941 When Administered in Patients With Locally Advanced or Metastatic Solid Tumors

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.

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.

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 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).

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.

Accumulation ratio was calculated as: AUC0-24 at Cycle 1 Day 18 divided by AUC0-24 at Cycle 1 Day 1.

Accumulation ratio was calculated as: AUC0-24 at Cycle 1 Day 21 divided by AUC0-24 at Cycle 1 Day 1.

Stage 2 PK data were reported for each indication specific cohort separately.

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.

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.

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.

Stage 2A PK data were reported for each indication specific cohort separately.

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.

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.

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.

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.

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.

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.

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 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.

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.

Genentech, Inc.

Participants received a single oral dose of pictilisib 80 mg capsules on Day 1 of Cycle 1 and a single oral dose of cobimetinib 20 mg capsules on Day 3 of Cycle 1, followed by continuous 21-day dosing with both cobimetinib and pictilisib at same doses from Days 8 to 28 and then 7 days off study drugs from Days 29 to 35 (Cycle 1 = 35 days). In subsequent cycles (28-day cycles), participants received 21-day dosing with both cobimetinib and pictilisib at same doses from Days 1 to 21 and then 7 days off study drugs from Days 22 to 28. Treatment continued until disease progression, unacceptable toxicity, or any other discontinuation criterion was met.

S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib

Participants received a single oral dose of pictilisib 100 mg capsules on Day 1 of Cycle 1 and a single oral dose of cobimetinib 20 mg capsules on Day 3 of Cycle 1, followed by continuous 21-day dosing with both cobimetinib and pictilisib at same doses from Days 8 to 28 and then 7 days off study drugs from Days 29 to 35 (Cycle 1 = 35 days). In subsequent cycles (28-day cycles), participants received 21-day dosing with both cobimetinib and pictilisib at same doses from Days 1 to 21 and then 7 days off study drugs from Days 22 to 28. Treatment continued until disease progression, unacceptable toxicity, or any other discontinuation criterion was met.

S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib

Participants received a single oral dose of pictilisib 80 mg capsules on Day 1 of Cycle 1 and a single oral dose of cobimetinib 40 mg capsules on Day 3 of Cycle 1, followed by continuous 21-day dosing with both cobimetinib and pictilisib at same doses from Days 8 to 28 and then 7 days off study drugs from Days 29 to 35 (Cycle 1 = 35 days). In subsequent cycles (28-day cycles), participants received 21-day dosing with both cobimetinib and pictilisib at same doses from Days 1 to 21 and then 7 days off study drugs from Days 22 to 28. Treatment continued until disease progression, unacceptable toxicity, or any other discontinuation criterion was met.

S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib

Participants received cobimetinib 40 mg capsules and pictilisib 100 mg capsules from Days 1 to 21 and then 7 days off study drugs from Days 22 to 28 in continuous 28-day cycles. Treatment continued until disease progression, unacceptable toxicity, or any other discontinuation criterion was met. This arm included participants from S1 C4 as well as S2 expansion cohort.

S1 C4/S2 Expansion: 40 mg Cobimetinib + 100 mg Pictilisib

Participants received cobimetinib 40 mg capsules and pictilisib 130 mg capsules from Days 1 to 21 and then 7 days off study drugs from Days 22 to 28 in continuous 28-day cycles. Treatment continued until disease progression, unacceptable toxicity, or any other discontinuation criterion was met.

S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib

Participants received cobimetinib 60 mg capsules and pictilisib 100 mg capsules from Days 1 to 21 and then 7 days off study drugs from Days 22 to 28 in continuous 28-day cycles. Treatment continued until disease progression, unacceptable toxicity, or any other discontinuation criterion was met.

S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib

Participants received cobimetinib 80 mg capsules and pictilisib 100 mg capsules from Days 1 to 21 and then 7 days off study drugs from Days 22 to 28 in continuous 28-day cycles. Treatment continued until disease progression, unacceptable toxicity, or any other discontinuation criterion was met.

S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib

Participants received cobimetinib 100 mg capsules on Days 1, 4, 8, 11, 15, and 18 and pictilisib 130 mg capsules from Days 1 to 21 and then 7 days off study drugs from Days 22 to 28 in continuous 28-day cycles. Treatment continued until disease progression, unacceptable toxicity, or any other discontinuation criterion was met.

S1A CA: 100 mg Cobimetinib + 130 mg Pictilisib

Participants received cobimetinib 100 mg capsules on Days 1, 4, 8, 11, 15, and 18 and pictilisib 180 mg capsules from Days 1 to 21 and then 7 days off study drugs from Days 22 to 28 in continuous 28-day cycles. Treatment continued until disease progression, unacceptable toxicity, or any other discontinuation criterion was met.

S1A CB: 100 mg Cobimetinib + 180 mg Pictilisib

Participants received cobimetinib 125 mg capsules on Days 1, 4, 8, 11, 15, and 18 and pictilisib 130 mg capsules from Days 1 to 21 and then 7 days off study drugs from Days 22 to 28 in continuous 28-day cycles. Treatment continued until disease progression, unacceptable toxicity, or any other discontinuation criterion was met.

S1A CC: 125 mg Cobimetinib + 130 mg Pictilisib

Participants received cobimetinib 125 mg capsules on Days 1, 4, 8, 11, 15, and 18 and pictilisib 180 mg capsules from Days 1 to 21 and then 7 days off study drugs from Days 22 to 28 in continuous 28-day cycles. Treatment continued until disease progression, unacceptable toxicity, or any other discontinuation criterion was met. This arm included participants form S1A CD as well as S2A expansion cohort.

S1A CD/S2A Expension: 125 mg Cobimetinib + 180 mg Pictilisib

Participants received cobimetinib 125 mg capsules on Days 1, 4, 8, 11, 15, and 18 and pictilisib 245 mg capsules from Days 1 to 21 and then 7 days off study drugs from Days 22 to 28 in continuous 28-day cycles. Treatment continued until disease progression, unacceptable toxicity, or any other discontinuation criterion was met.

S1A CE: 125 mg Cobimetinib + 245 mg Pictilisib

Participants received cobimetinib 150 mg capsules on Days 1, 4, 8, 11, 15, and 18 and pictilisib 180 mg capsules from Days 1 to 21 and then 7 days off study drugs from Days 22 to 28 in continuous 28-day cycles. Treatment continued until disease progression, unacceptable toxicity, or any other discontinuation criterion was met.

S1A CF: 150 mg Cobimetinib + 180 mg Pictilisib

Participants received cobimetinib 150 mg capsules on Days 1, 4, 8, 11, 15, and 18 and pictilisib 245 mg capsules from Days 1 to 21 and then 7 days off study drugs from Days 22 to 28 in continuous 28-day cycles. Treatment continued until disease progression, unacceptable toxicity, or any other discontinuation criterion was met.

S1A CG: 150 mg Cobimetinib + 245 mg Pictilisib

Participants received cobimetinib 40 mg capsules and pictilisib 130 mg capsules from Days 1 to 7 and then from Days 15 to 21 in continuous 28-day cycles. Participants were off study drugs from Days 8 to 14 and from Days 22 to 28. Treatment continued until disease progression, unacceptable toxicity, or any other discontinuation criterion was met.

S1B CAX: 40 mg Cobimetinib + 130 mg Pictilisib

Participants received cobimetinib 40 mg capsules and pictilisib 180 mg capsules from Days 1 to 7 and then from Days 15 to 21 in continuous 28-day cycles. Participants were off study drugs from Days 8 to 14 and from Days 22 to 28. Treatment continued until disease progression, unacceptable toxicity, or any other discontinuation criterion was met.

S1B CBX: 40 mg Cobimetinib + 180 mg Pictilisib

Participants received cobimetinib 60 mg capsules and pictilisib 130 mg capsules from Days 1 to 7 and then from Days 15 to 21 in continuous 28-day cycles. Participants were off study drugs from Days 8 to 14 and from Days 22 to 28. Treatment continued until disease progression, unacceptable toxicity, or any other discontinuation criterion was met.

S1B CCX: 60 mg Cobimetinib + 130 mg Pictilisib

Participants received cobimetinib 60 mg capsules and pictilisib 180 mg capsules from Days 1 to 7 and then from Days 15 to 21 in continuous 28-day cycles. Participants were off study drugs from Days 8 to 14 and from Days 22 to 28. Treatment continued until disease progression, unacceptable toxicity, or any other discontinuation criterion was met.

S1B CDX: 60 mg Cobimetinib + 180 mg Pictilisib

All participants who received cobimetinib and pictilisib in any dose combination until disease progression, unacceptable toxicity, or any other discontinuation criterion was met.

All Participants

Age, Continuous

Gender

The study was terminated prior to the initiation of Stage 2B and as per changes in planned analysis the data for duration of objective response and PFS were not analyzed.

Medical Communications

Participants received cobimetinib 40 mg capsules and pictilisib 100 mg capsules from Days 1 to 21 and then 7 days off study drugs from Days 22 to 28 in continuous 28-day cycles. Treatment continued until disease progression, unacceptable toxicity, or any other discontinuation criterion was met.

S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib

Participants received cobimetinib 125 mg capsules on Days 1, 4, 8, 11, 15, and 18 and pictilisib 180 mg capsules from Days 1 to 21 and then 7 days off study drugs from Days 22 to 28 in continuous 28-day cycles. Treatment continued until disease progression, unacceptable toxicity, or any other discontinuation criterion was met.

S1A CD: 125 mg Cobimetinib + 180 mg Pictilisib

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.

Number of Participants With Dose-Limiting Toxicities (DLTs) During Dose Escalation Stages 1, 1A and 1B

Stage 1: Cobimetinib (n = 44)

Stage 1: Pictilisib (n = 44)

Stage 1A: Cobimetinib (n = 34)

Stage 1A: Pictilisib (n = 34)

Stage 1B: Cobimetinib (n = 20)

Stage 1B: Pictilisib (n = 20)

All participants who received cobimetinib and pictilisib in any dose combination during Stages 1, 1A, and 1B, until disease progression, unacceptable toxicity, or any other discontinuation criterion was met.

All Participants - Stages 1, 1A, 1B

Safety-evaluable population. Here, number of participants analyzed = participants who were evaluable for this outcome and n = participants evaluable for specified categories.

Maximum Tolerated Combination Doses of Cobimetinib and Pictilisib During Dose-Escalation Stages 1, 1A and 1B

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.

Time of Maximum Concentration (Tmax) of Cobimetinib on Day 3 - Stage 1, Cohorts 1-3

PK population. Here, number of participants analyzed = participants who were evaluable for this outcome.

Maximum Plasma Concentration (Cmax) of Cobimetinib on Day 3 - Stage 1, Cohorts 1-3

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

Tmax of Pictilisib on Day 1 - Stage 1, Cohorts 1-3

Cmax of Pictilisib on Day 1 - Stage 1, Cohorts 1-3

AUC0-24 of Pictilisib on Day 1 - Stage 1, Cohorts 1-3

Tmax of Cobimetinib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts

Cmax of Cobimetinib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts

AUC0-24 of Cobimetinib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts

Tmax of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts

Cmax of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts

AUC0-24 of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts

Terminal Half-life (t1/2) of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts

Apparent Clearance (CL/F) of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts

Accumulation Ratio of Cobimetinib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts

Tmax of Pictilisib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts

Cmax of Pictilisib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts

AUC0-24 of Pictilisib on Cycle 1 Day 1 (Cycle 1 Day 8 for Cohorts 1-3) - Stage 1 All Cohorts

Tmax of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts

Cmax of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts

AUC0-24 of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts

t1/2 of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts

CL/F of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts

Accumulation Ratio of Pictilisib on Cycle 1 Day 21 (Cycle 1 Day 28 for Cohorts 1-3) - Stage 1 All Cohorts

Tmax of Cobimetinib on Cycle 1 Day 1 - Stage 1A All Cohorts

Cmax of Cobimetinib on Cycle 1 Day 1 - Stage 1A All Cohorts

AUC0-24 of Cobimetinib on Cycle 1 Day 1 - Stage 1A All Cohorts

Tmax of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts

Cmax of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts

AUC0-24 of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts

t1/2 of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts

CL/F of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts

Accumulation Ratio of Cobimetinib on Cycle 1 Day 18 - Stage 1A All Cohorts

Tmax of Pictilisib on Cycle 1 Day 1 - Stage 1A All Cohorts

Cmax of Pictilisib on Cycle 1 Day 1 - Stage 1A All Cohorts

AUC0-24 of Pictilisib on Cycle 1 Day 1 - Stage 1A All Cohorts

Tmax of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts

Cmax of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts

AUC0-24 of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts

t1/2 of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts

CL/F of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts

Accumulation Ratio of Pictilisib on Cycle 1 Day 18 - Stage 1A All Cohorts

Tmax of Cobimetinib on Cycle 1 Day 1 - Stage 1B All Cohorts

Cmax of Cobimetinib on Cycle 1 Day 1 - Stage 1B All Cohorts

AUC0-24 of Cobimetinib on Cycle 1 Day 1 - Stage 1B All Cohorts

Tmax of Cobimetinib on Cycle 1 Day 21 - Stage 1B All Cohorts

Cmax of Cobimetinib on Cycle 1 Day 21 - Stage 1B All Cohorts

AUC0-24 of Cobimetinib on Cycle 1 Day 21 - Stage 1B All Cohorts

CL/F of Cobimetinib on Cycle 1 Day 21 - Stage 1B All Cohorts

Accumulation Ratio of Cobimetinib on Cycle 1 Day 21 - Stage 1B All Cohorts

Tmax of Pictilisib on Cycle 1 Day 1 - Stage 1B All Cohorts

Cmax of Pictilisib on Cycle 1 Day 1 - Stage 1B All Cohorts

AUC0-24 of Pictilisib on Cycle 1 Day 1 - Stage 1B All Cohorts

Tmax of Pictilisib on Cycle 1 Day 21 - Stage 1B All Cohorts

Cmax of Pictilisib on Cycle 1 Day 21 - Stage 1B All Cohorts

AUC0-24 of Pictilisib on Cycle 1 Day 21 - Stage 1B All Cohorts

CL/F of Pictilisib on Cycle 1 Day 21 - Stage 1B All Cohorts

Accumulation Ratio of Pictilisib on Cycle 1 Day 21 - Stage 1B All Cohorts

Participants with EGFR T790M mutant and EGFR inhibitor-progressing NSCLC received cobimetinib 40 mg capsules and pictilisib 100 mg capsules from Days 1 to 21 and then 7 days off study drugs from Days 22 to 28 in continuous 28-day cycles. Treatment continued until disease progression, unacceptable toxicity, or any other discontinuation criterion was met.

S2 EGFR T790M NSCLC: 40 mg Cobimetinib + 100 mg Pictilisib

Participants with KRAS NSCLC received cobimetinib 40 mg capsules and pictilisib 100 mg capsules from Days 1 to 21 and then 7 days off study drugs from Days 22 to 28 in continuous 28-day cycles. Treatment continued until disease progression, unacceptable toxicity, or any other discontinuation criterion was met.

S2 KRAS NSCLC: 40 mg Cobimetinib + 100 mg Pictilisib

Participants with KRAS CRC received cobimetinib 40 mg capsules and pictilisib 100 mg capsules from Days 1 to 21 and then 7 days off study drugs from Days 22 to 28 in continuous 28-day cycles. Treatment continued until disease progression, unacceptable toxicity, or any other discontinuation criterion was met.

S2 KRAS CRC: 40 mg Cobimetinib + 100 mg Pictilisib

Participants with pancreatic adenocarcinoma received cobimetinib 40 mg capsules and pictilisib 100 mg capsules from Days 1 to 21 and then 7 days off study drugs from Days 22 to 28 in continuous 28-day cycles. Treatment continued until disease progression, unacceptable toxicity, or any other discontinuation criterion was met.

S2 Pancreatic: 40 mg Cobimetinib + 100 mg Pictilisib

Tmax of Cobimetinib on Cycle 1 Day 1 - Stage 2 Individual Indication Specific Cohorts

Cmax of Cobimetinib on Cycle 1 Day 1 - Stage 2 Individual Indication Specific Cohorts

AUC0-24 of Cobimetinib on Cycle 1 Day 1 - Stage 2 All Cohorts

Tmax of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts

Cmax of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts

AUC0-24 of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts

t1/2 of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts

CL/F of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts

Accumulation Ratio of Cobimetinib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts

Tmax of Pictilisib on Cycle 1 Day 1 - Stage 2 Individual Indication Specific Cohorts

Cmax of Pictilisib on Cycle 1 Day 1 - Stage 2 Individual Indication Specific Cohorts

AUC0-24 of Pictilisib on Cycle 1 Day 1 - Stage 2 Individual Indication Specific Cohorts

Tmax of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts

Cmax of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts

AUC0-24 of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts

t1/2 of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts

CL/F of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts

Accumulation Ratio of Pictilisib on Cycle 1 Day 21 - Stage 2 Individual Indication Specific Cohorts

Participants with EGFR T790M mutant and EGFR inhibitor-progressing NSCLC received cobimetinib 125 mg capsules on Days 1, 4, 8, 11, 15, and 18 and pictilisib 180 mg capsules from Days 1 to 21 and then 7 days off study drugs from Days 22 to 28 in continuous 28-day cycles. Treatment continued until disease progression, unacceptable toxicity, or any other discontinuation criterion was met.

S2A EGFR T790M NSCLC: 125 mg Cobimetinib + 180 mg Pictilisib

Participants with KRAS NSCLC received cobimetinib 125 mg capsules on Days 1, 4, 8, 11, 15, and 18 and pictilisib 180 mg capsules from Days 1 to 21 and then 7 days off study drugs from Days 22 to 28 in continuous 28-day cycles. Treatment continued until disease progression, unacceptable toxicity, or any other discontinuation criterion was met.

S2A KRAS NSCLC: 125 mg Cobimetinib + 180 mg Pictilisib

Participants with KRAS CRC received cobimetinib 125 mg capsules on Days 1, 4, 8, 11, 15, and 18 and pictilisib 180 mg capsules from Days 1 to 21 and then 7 days off study drugs from Days 22 to 28 in continuous 28-day cycles. Treatment continued until disease progression, unacceptable toxicity, or any other discontinuation criterion was met.

S2A KRAS CRC: 125 mg Cobimetinib + 180 mg Pictilisib

Participants with pancreatic adenocarcinoma received cobimetinib 125 mg capsules on Days 1, 4, 8, 11, 15, and 18 and pictilisib 180 mg capsules from Days 1 to 21 and then 7 days off study drugs from Days 22 to 28 in continuous 28-day cycles. Treatment continued until disease progression, unacceptable toxicity, or any other discontinuation criterion was met.

S2A Pancreatic: 125 mg Cobimetinib + 180 mg Pictilisib

Participants with KRAS mutant endometrioid carcinoma received cobimetinib 125 mg capsules on Days 1, 4, 8, 11, 15, and 18 and pictilisib 180 mg capsules from Days 1 to 21 and then 7 days off study drugs from Days 22 to 28 in continuous 28-day cycles. Treatment continued until disease progression, unacceptable toxicity, or any other discontinuation criterion was met.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Safety, Tolerability and Pharmacokinetics of Cobimetinib in Combination With Pictilisib in Patients With Locally Advanced or Metastatic Solid Tumors	NCT00996892	Solid Tumors	Cobimetinib Pictilisib	18 Years -	Genentech, Inc.
COPANLISIB (BAY80-6946) Drug-drug Interaction and Cardiovascular Safety Study in Advanced Solid Tumor and Non-Hodgkin's Lymphoma Patients	NCT02253420	Medical Oncolog...	Copanlisib (BAY... Itraconazole Rifampin Copanlisib (BAY...	18 Years -	Bayer
Safety, Tolerability and Pharmacokinetics of Cobimetinib in Combination With Pictilisib in Patients With Locally Advanced or Metastatic Solid Tumors	NCT00996892	Solid Tumors	Cobimetinib Pictilisib	18 Years -	Genentech, Inc.

Spots Global Cancer Trial Database for pi3 kinase inhibitor