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Solid TumorsPhase 1NCT00996892

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

A Phase 1 study testing Cobimetinib and Pictilisib in people with Solid Tumors, run by Genentech, Inc. at 6 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Solid Tumors
What is being tested?
Cobimetinib and Pictilisib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
178 participants
Where
6 sitesUnited States
Study dates
Nov 2009to Mar 2014
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Study site

    Baltimore, Maryland, 21231

  • Study site

    Boston, Massachusetts, 02114

  • Study site

    Boston, Massachusetts, 02215

  • Study site

    Detroit, Michigan, 48201

  • Study site

    Nashville, Tennessee, 37203

  • Study site

    Oklahoma City, Oklahoma, 73104

Other trials in United States

About this study

Official title: 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

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.

Conditions
Solid Tumors
Being tested
Cobimetinib, Pictilisib
Keywords
GDC0941, GDC0973, MEK, MEK Inhibitor, PI3K, PI3K Inhibitor, PI3 Kinase, PI3 Kinase Inhibitor
Medical subject headings
Hereditary Sensory and Autonomic Neuropathies

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CobimetinibDrug

    Also called GDC-0973, XL518

    Repeated oral dosing.

  • PictilisibDrug

    Also called GDC-0941

    Repeated oral dosing.

Study groups in NCT00996892
Study groupRoleWhat they receive
Dose Escalation Stage 1: Cobimetinib + PictilisibExperimentalParticipants 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.
Receives: Drug: Cobimetinib; Drug: Pictilisib
Dose Escalation Stage 1A: Cobimetinib + PictilisibExperimentalParticipants 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.
Receives: Drug: Cobimetinib; Drug: Pictilisib
Dose Escalation Stage 1B: Cobimetinib + PictilisibExperimentalParticipants 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.
Receives: Drug: Cobimetinib; Drug: Pictilisib
Dose Expansion Stage 2: Cobimetinib + PictilisibExperimentalParticipants 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).
Receives: Drug: Cobimetinib; Drug: Pictilisib
Dose Expansion Stage 2A: Cobimetinib + PictilisibExperimentalParticipants 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.
Receives: Drug: Cobimetinib; Drug: Pictilisib
Dose Expansion Stage 2B: Cobimetinib + PictilisibExperimentalParticipants 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.
Receives: Drug: Cobimetinib; Drug: Pictilisib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Cohorts 1-3: Day 1 to Day 35, All other cohorts: Day 1 to Day 28

  2. 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.

    Measured: Cohorts 1-3: Day 1 to Day 35, All other cohorts: Day 1 to Day 28

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

    Measured: 0-4 hours pre-cobimetinib (Pr-C) dose, 0.5, 2, 4, 6 hours post-cobimetinib (Po-C) dose on Day 3, Day 4

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

    Measured: 0-4 hours Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Day 3, Day 4

  5. 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

    Measured: 0-4 hours Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Day 3, Day 4

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

    Measured: 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

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

    Measured: 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

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

    Measured: 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 outcomes (91)

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

    Measured: 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

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

    Measured: 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

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

    Measured: 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

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

    Measured: 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

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

    Measured: 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

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

    Measured: 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

  7. 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.

    Measured: 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

  8. 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.

    Measured: 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

  9. 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).

    Measured: 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

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

    Measured: 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

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

    Measured: 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

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

    Measured: 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

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

    Measured: 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

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

    Measured: 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

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

    Measured: 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

  16. 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.

    Measured: 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

  17. 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.

    Measured: 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

  18. 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).

    Measured: 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

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

    Measured: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 15-17

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

    Measured: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 15-17

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

    Measured: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Days 2

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

    Measured: 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

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

    Measured: 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

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

    Measured: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 18, Cycle 1 Day 19

  25. 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.

    Measured: 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

  26. 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.

    Measured: 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

  27. 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.

    Measured: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Days 1 and 18, Cycle 1 Days 2, 19

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

    Measured: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 15-17

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

    Measured: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 15-17

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

    Measured: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Days 2

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

    Measured: 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

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

    Measured: 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

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

    Measured: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 18, Cycle 1 Day 19

  34. 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.

    Measured: 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

  35. 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.

    Measured: 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

  36. 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.

    Measured: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Days 1 and 18, Cycle 1 Days 2, 19

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

    Measured: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Day 2

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

    Measured: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Day 2

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

    Measured: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Day 2

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

    Measured: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22

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

    Measured: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22

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

    Measured: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22

  43. 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.

    Measured: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22

  44. 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.

    Measured: 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

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

    Measured: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Day 2

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

    Measured: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Day 2

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

    Measured: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Day 2

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

    Measured: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22

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

    Measured: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22

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

    Measured: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22

  51. 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.

    Measured: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22

  52. 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.

    Measured: 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

  53. 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.

    Measured: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 14

  54. 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.

    Measured: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 14

  55. 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.

    Measured: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Days 2

  56. 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.

    Measured: 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

  57. 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.

    Measured: 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

  58. 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.

    Measured: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22

  59. 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.

    Measured: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22

  60. 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.

    Measured: 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

  61. 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.

    Measured: 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

  62. 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.

    Measured: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 14

  63. 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.

    Measured: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 14

  64. 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.

    Measured: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Days 2

  65. 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.

    Measured: 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

  66. 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.

    Measured: 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

  67. 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.

    Measured: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22

  68. 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.

    Measured: 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

  69. 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.

    Measured: 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

  70. 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.

    Measured: 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

  71. 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.

    Measured: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 15-17

  72. 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.

    Measured: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 15-17

  73. 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.

    Measured: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Days 2

  74. 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.

    Measured: 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

  75. 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.

    Measured: 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

  76. 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.

    Measured: 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

  77. 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.

    Measured: 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

  78. 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.

    Measured: 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

  79. 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.

    Measured: 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

  80. 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.

    Measured: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 15-17

  81. 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.

    Measured: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Days 2, 8, 15-17

  82. 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.

    Measured: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Days 2

  83. 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.

    Measured: 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

  84. 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.

    Measured: 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

  85. 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.

    Measured: 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

  86. 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.

    Measured: 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

  87. 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.

    Measured: 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

  88. 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.

    Measured: 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

  89. 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.

    Measured: Up to 30 days after last dose (last dose = up to Cycle 15, cycle length = 28 days)

  90. 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.

    Measured: Up to 30 days after last dose (last dose = up to Cycle 15, cycle length = 28 days)

  91. 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.

    Measured: Up to 30 days after last dose (last dose = up to Cycle 15, cycle length = 28 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Oct 2009 (estimated)
  2. Study startNov 2009
  3. Primary completionMar 2014
  4. Study completionMar 2014

Why it stopped: A recommended Phase 2 dose and schedule was not identified and the study was terminated before initiation of Stage 2B.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
178 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00996892
Sponsor's protocol ID
MEK4752g
Other IDs
GO01330
Status last verified
Nov 2016
First submitted
12 Oct 2009
Last updated
30 Dec 2016

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cobimetinib and Pictilisib in people with Solid Tumors, run by Genentech, Inc. at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 30 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Dec 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Dose-Limiting Toxicities (DLTs) During Dose Escalation Stages 1, 1A and 1B (time frame: Cohorts 1-3: Day 1 to Day 35, All other cohorts: Day 1 to Day 28). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00996892.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Dec 2016.

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