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

This study has been terminated.
(A recommended Phase 2 dose and schedule was not identified and the study was terminated before initiation of Stage 2B.)
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT00996892
First received: October 12, 2009
Last updated: November 4, 2016
Last verified: November 2016
Results First Received: March 3, 2016  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition: Solid Tumors
Interventions: Drug: Cobimetinib
Drug: Pictilisib

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Study was terminated before initiation of Stage 2B; hence Stage 2B cohorts were not applicable.

Reporting Groups
  Description
S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib Stage 1 Cohort 1 (S1 C1): Participants received a single oral dose of pictilisib 80 milligrams (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 Stage 1 Cohort 2 (S1 C2): 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 C3: 40 mg Cobimetinib + 80 mg Pictilisib Stage 1 Cohort 3 (S1 C3): 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 C4: 40 mg Cobimetinib + 100 mg Pictilisib Stage 1 Cohort 4 (S1 C4): 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 C5: 40 mg Cobimetinib + 130 mg Pictilisib Stage 1 Cohort 5 (S1 C5): 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 C6: 60 mg Cobimetinib + 100 mg Pictilisib Stage 1 Cohort 6 (S1 C6): 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 C6A: 80 mg Cobimetinib + 100 mg Pictilisib Stage 1 Cohort 6A (S1 C6A): 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.
S1A CA: 100 mg Cobimetinib + 130 mg Pictilisib Stage 1A Cohort A (S1A CA): 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 CB: 100 mg Cobimetinib + 180 mg Pictilisib Stage 1A Cohort B (S1A CB): 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 CC: 125 mg Cobimetinib + 130 mg Pictilisib Stage 1A Cohort C (S1A CC): 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 CD: 125 mg Cobimetinib + 180 mg Pictilisib Stage 1A Cohort D (S1A CD): 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 CE: 125 mg Cobimetinib + 245 mg Pictilisib Stage 1A Cohort E (S1A CE): 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 CF: 150 mg Cobimetinib + 180 mg Pictilisib Stage 1A Cohort F (S1A CF): 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 CG: 150 mg Cobimetinib + 245 mg Pictilisib Stage 1A Cohort G (S1A CG): 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.
S1B CAX: 40 mg Cobimetinib + 130 mg Pictilisib Stage 1B Cohort AX (S1B CAX): 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 CBX: 40 mg Cobimetinib + 180 mg Pictilisib Stage 1B Cohort BX (S1B CBX): 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 CCX: 60 mg Cobimetinib + 130 mg Pictilisib Stage 1B Cohort CX (S1B CCX): 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 CDX: 60 mg Cobimetinib + 180 mg Pictilisib Stage 1B Cohort DX (S1B CDX): 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.
S2 Expansion: 40 mg Cobimetinib + 100 mg Pictilisib Stage 2 (S2) expansion cohort: 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 indication specific cohort included 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).
S2A Expansion: 125 mg Cobimetinib + 180 mg Pictilisib Stage 2A (S2A) expansion cohort: 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 indication specific cohort included participants with KRAS mutant NSCLC; EGFR T790M mutant and EGFR inhibitor-progressing NSCLC; pancreatic adenocarcinoma; KRAS mutant CRC, and KRAS mutant endometrioid carcinoma.

Participant Flow for 5 periods

Period 1:   Dose-Escalation Stage 1
    S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib   S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib   S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib   S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib   S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib   S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib   S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib   S1A CA: 100 mg Cobimetinib + 130 mg Pictilisib   S1A CB: 100 mg Cobimetinib + 180 mg Pictilisib   S1A CC: 125 mg Cobimetinib + 130 mg Pictilisib   S1A CD: 125 mg Cobimetinib + 180 mg Pictilisib   S1A CE: 125 mg Cobimetinib + 245 mg Pictilisib   S1A CF: 150 mg Cobimetinib + 180 mg Pictilisib   S1A CG: 150 mg Cobimetinib + 245 mg Pictilisib   S1B CAX: 40 mg Cobimetinib + 130 mg Pictilisib   S1B CBX: 40 mg Cobimetinib + 180 mg Pictilisib   S1B CCX: 60 mg Cobimetinib + 130 mg Pictilisib   S1B CDX: 60 mg Cobimetinib + 180 mg Pictilisib   S2 Expansion: 40 mg Cobimetinib + 100 mg Pictilisib   S2A Expansion: 125 mg Cobimetinib + 180 mg Pictilisib
STARTED   4   3   3   9   11   10   4   0   0   0   0   0   0   0   0   0   0   0   0   0 
COMPLETED   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0 
NOT COMPLETED   4   3   3   9   11   10   4   0   0   0   0   0   0   0   0   0   0   0   0   0 
Adverse Event                0                0                0                2                0                0                1                0                0                0                0                0                0                0                0                0                0                0                0                0 
Death                1                0                0                0                0                1                0                0                0                0                0                0                0                0                0                0                0                0                0                0 
Physician Decision                1                0                0                1                0                1                2                0                0                0                0                0                0                0                0                0                0                0                0                0 
Withdrawal by Subject                0                1                0                2                1                1                1                0                0                0                0                0                0                0                0                0                0                0                0                0 
Disease Progression                2                2                3                4                10                7                0                0                0                0                0                0                0                0                0                0                0                0                0                0 

Period 2:   Dose-Escalation Stage 1A
    S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib   S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib   S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib   S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib   S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib   S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib   S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib   S1A CA: 100 mg Cobimetinib + 130 mg Pictilisib   S1A CB: 100 mg Cobimetinib + 180 mg Pictilisib   S1A CC: 125 mg Cobimetinib + 130 mg Pictilisib   S1A CD: 125 mg Cobimetinib + 180 mg Pictilisib   S1A CE: 125 mg Cobimetinib + 245 mg Pictilisib   S1A CF: 150 mg Cobimetinib + 180 mg Pictilisib   S1A CG: 150 mg Cobimetinib + 245 mg Pictilisib   S1B CAX: 40 mg Cobimetinib + 130 mg Pictilisib   S1B CBX: 40 mg Cobimetinib + 180 mg Pictilisib   S1B CCX: 60 mg Cobimetinib + 130 mg Pictilisib   S1B CDX: 60 mg Cobimetinib + 180 mg Pictilisib   S2 Expansion: 40 mg Cobimetinib + 100 mg Pictilisib   S2A Expansion: 125 mg Cobimetinib + 180 mg Pictilisib
STARTED   0   0   0   0   0   0   0   3   3   4   7   9   8   5   0   0   0   0   0   0 
COMPLETED   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0 
NOT COMPLETED   0   0   0   0   0   0   0   3   3   4   7   9   8   5   0   0   0   0   0   0 
Adverse Event                0                0                0                0                0                0                0                0                0                0                1                0                0                1                0                0                0                0                0                0 
Death                0                0                0                0                0                0                0                0                0                2                0                1                1                0                0                0                0                0                0                0 
Physician Decision                0                0                0                0                0                0                0                1                0                0                0                0                0                0                0                0                0                0                0                0 
Withdrawal by Subject                0                0                0                0                0                0                0                0                0                1                1                1                1                0                0                0                0                0                0                0 
Disease Progression                0                0                0                0                0                0                0                2                3                1                5                7                6                4                0                0                0                0                0                0 

Period 3:   Dose-Escalation Stage 1B
    S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib   S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib   S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib   S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib   S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib   S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib   S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib   S1A CA: 100 mg Cobimetinib + 130 mg Pictilisib   S1A CB: 100 mg Cobimetinib + 180 mg Pictilisib   S1A CC: 125 mg Cobimetinib + 130 mg Pictilisib   S1A CD: 125 mg Cobimetinib + 180 mg Pictilisib   S1A CE: 125 mg Cobimetinib + 245 mg Pictilisib   S1A CF: 150 mg Cobimetinib + 180 mg Pictilisib   S1A CG: 150 mg Cobimetinib + 245 mg Pictilisib   S1B CAX: 40 mg Cobimetinib + 130 mg Pictilisib   S1B CBX: 40 mg Cobimetinib + 180 mg Pictilisib   S1B CCX: 60 mg Cobimetinib + 130 mg Pictilisib   S1B CDX: 60 mg Cobimetinib + 180 mg Pictilisib   S2 Expansion: 40 mg Cobimetinib + 100 mg Pictilisib   S2A Expansion: 125 mg Cobimetinib + 180 mg Pictilisib
STARTED   0   0   0   0   0   0   0   0   0   0   0   0   0   0   4   3   3   5   0   0 
COMPLETED   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0 
NOT COMPLETED   0   0   0   0   0   0   0   0   0   0   0   0   0   0   4   3   3   5   0   0 
Physician Decision                0                0                0                0                0                0                0                0                0                0                0                0                0                0                0                0                0                2                0                0 
Disease Progression                0                0                0                0                0                0                0                0                0                0                0                0                0                0                4                3                3                3                0                0 

Period 4:   Expansion Stage 2
    S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib   S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib   S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib   S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib   S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib   S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib   S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib   S1A CA: 100 mg Cobimetinib + 130 mg Pictilisib   S1A CB: 100 mg Cobimetinib + 180 mg Pictilisib   S1A CC: 125 mg Cobimetinib + 130 mg Pictilisib   S1A CD: 125 mg Cobimetinib + 180 mg Pictilisib   S1A CE: 125 mg Cobimetinib + 245 mg Pictilisib   S1A CF: 150 mg Cobimetinib + 180 mg Pictilisib   S1A CG: 150 mg Cobimetinib + 245 mg Pictilisib   S1B CAX: 40 mg Cobimetinib + 130 mg Pictilisib   S1B CBX: 40 mg Cobimetinib + 180 mg Pictilisib   S1B CCX: 60 mg Cobimetinib + 130 mg Pictilisib   S1B CDX: 60 mg Cobimetinib + 180 mg Pictilisib   S2 Expansion: 40 mg Cobimetinib + 100 mg Pictilisib   S2A Expansion: 125 mg Cobimetinib + 180 mg Pictilisib
STARTED   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0   35   0 
COMPLETED   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0 
NOT COMPLETED   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0   35   0 
Adverse Event                0                0                0                0                0                0                0                0                0                0                0                0                0                0                0                0                0                0                3                0 
Death                0                0                0                0                0                0                0                0                0                0                0                0                0                0                0                0                0                0                2                0 
Physician Decision                0                0                0                0                0                0                0                0                0                0                0                0                0                0                0                0                0                0                1                0 
Withdrawal by Subject                0                0                0                0                0                0                0                0                0                0                0                0                0                0                0                0                0                0                1                0 
Disease Progression                0                0                0                0                0                0                0                0                0                0                0                0                0                0                0                0                0                0                28                0 

Period 5:   Expansion Stage 2A
    S1 C1: 20 mg Cobimetinib + 80 mg Pictilisib   S1 C2: 20 mg Cobimetinib + 100 mg Pictilisib   S1 C3: 40 mg Cobimetinib + 80 mg Pictilisib   S1 C4: 40 mg Cobimetinib + 100 mg Pictilisib   S1 C5: 40 mg Cobimetinib + 130 mg Pictilisib   S1 C6: 60 mg Cobimetinib + 100 mg Pictilisib   S1 C6A: 80 mg Cobimetinib + 100 mg Pictilisib   S1A CA: 100 mg Cobimetinib + 130 mg Pictilisib   S1A CB: 100 mg Cobimetinib + 180 mg Pictilisib   S1A CC: 125 mg Cobimetinib + 130 mg Pictilisib   S1A CD: 125 mg Cobimetinib + 180 mg Pictilisib   S1A CE: 125 mg Cobimetinib + 245 mg Pictilisib   S1A CF: 150 mg Cobimetinib + 180 mg Pictilisib   S1A CG: 150 mg Cobimetinib + 245 mg Pictilisib   S1B CAX: 40 mg Cobimetinib + 130 mg Pictilisib   S1B CBX: 40 mg Cobimetinib + 180 mg Pictilisib   S1B CCX: 60 mg Cobimetinib + 130 mg Pictilisib   S1B CDX: 60 mg Cobimetinib + 180 mg Pictilisib   S2 Expansion: 40 mg Cobimetinib + 100 mg Pictilisib   S2A Expansion: 125 mg Cobimetinib + 180 mg Pictilisib
STARTED   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0   45 
COMPLETED   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0 
NOT COMPLETED   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0   0   45 
Adverse Event                0                0                0                0                0                0                0                0                0                0                0                0                0                0                0                0                0                0                0                8 
Physician Decision                0                0                0                0                0                0                0                0                0                0                0                0                0                0                0                0                0                0                0                2 
Withdrawal by Subject                0                0                0                0                0                0                0                0                0                0                0                0                0                0                0                0                0                0                0                4 
Disease Progression                0                0                0                0                0                0                0                0                0                0                0                0                0                0                0                0                0                0                0                31 



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All enrolled participants.

Reporting Groups
  Description
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.

Baseline Measures
   All Participants 
Overall Participants Analyzed 
[Units: Participants]
 178 
Age 
[Units: Years]
Mean (Standard Deviation)
 56.6  (12.0) 
Gender 
[Units: Participants]
Count of Participants
 
Female      109  61.2% 
Male      69  38.8% 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   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 ]

2.  Primary:   Maximum Tolerated Combination Doses of Cobimetinib and Pictilisib 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 ]

3.  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 ]

4.  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 ]

5.  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 ]

6.  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 ]

7.  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 ]

8.  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 ]

9.  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 ]

10.  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 ]

11.  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 ]

12.  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 ]

13.  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 ]

14.  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 ]

15.  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   [ 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 ]

16.  Secondary:   Apparent Clearance (CL/F) 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 ]

17.  Secondary:   Accumulation Ratio 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 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 ]

18.  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 ]

19.  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 ]

20.  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 ]

21.  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 ]

22.  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 ]

23.  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 ]

24.  Secondary:   t1/2 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 ]

25.  Secondary:   CL/F 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 ]

26.  Secondary:   Accumulation Ratio 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 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 ]

27.  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 ]

28.  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 ]

29.  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 ]

30.  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 ]

31.  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 ]

32.  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 ]

33.  Secondary:   t1/2 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 ]

34.  Secondary:   CL/F 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 ]

35.  Secondary:   Accumulation Ratio 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 Days 1 and 18, Cycle 1 Days 2, 19 ]

36.  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 ]

37.  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 ]

38.  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 ]

39.  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 ]

40.  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 ]

41.  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 ]

42.  Secondary:   t1/2 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 ]

43.  Secondary:   CL/F 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 ]

44.  Secondary:   Accumulation Ratio 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 Days 1 and 18, Cycle 1 Days 2, 19 ]

45.  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 ]

46.  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 ]

47.  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 ]

48.  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 ]

49.  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 ]

50.  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 ]

51.  Secondary:   CL/F 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 ]

52.  Secondary:   Accumulation Ratio 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 Days 1 and 21, Cycle 1 Days 2 and 22 ]

53.  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 ]

54.  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 ]

55.  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 ]

56.  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 ]

57.  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 ]

58.  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 ]

59.  Secondary:   CL/F 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 ]

60.  Secondary:   Accumulation Ratio 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 Days 1 and 21, Cycle 1 Days 2 and 22 ]

61.  Secondary:   Tmax of Cobimetinib on Cycle 1 Day 1 – Stage 2 Individual Indication Specific 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, 14 ]

62.  Secondary:   Cmax of Cobimetinib on Cycle 1 Day 1 – Stage 2 Individual Indication Specific 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, 14 ]

63.  Secondary:   AUC0-24 of Cobimetinib on Cycle 1 Day 1 – Stage 2 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 ]

64.  Secondary:   Tmax of Cobimetinib on Cycle 1 Day 21 – Stage 2 Individual Indication Specific Cohorts   [ 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 ]

65.  Secondary:   Cmax of Cobimetinib on Cycle 1 Day 21 – Stage 2 Individual Indication Specific Cohorts   [ 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 ]

66.  Secondary:   AUC0-24 of Cobimetinib on Cycle 1 Day 21 – Stage 2 Individual Indication Specific Cohorts   [ Time Frame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22 ]

67.  Secondary:   t1/2 of Cobimetinib on Cycle 1 Day 21 – Stage 2 Individual Indication Specific Cohorts   [ Time Frame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 21, Cycle 1 Day 22 ]

68.  Secondary:   CL/F of Cobimetinib on Cycle 1 Day 21 – Stage 2 Individual Indication Specific Cohorts   [ 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 ]

69.  Secondary:   Accumulation Ratio of Cobimetinib on Cycle 1 Day 21 – Stage 2 Individual Indication Specific Cohorts   [ 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 ]

70.  Secondary:   Tmax of Pictilisib on Cycle 1 Day 1 – Stage 2 Individual Indication Specific 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, 14 ]

71.  Secondary:   Cmax of Pictilisib on Cycle 1 Day 1 – Stage 2 Individual Indication Specific 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, 14 ]

72.  Secondary:   AUC0-24 of Pictilisib on Cycle 1 Day 1 – Stage 2 Individual Indication Specific Cohorts   [ Time Frame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Days 2 ]

73.  Secondary:   Tmax of Pictilisib on Cycle 1 Day 21 – Stage 2 Individual Indication Specific Cohorts   [ 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 ]

74.  Secondary:   Cmax of Pictilisib on Cycle 1 Day 21 – Stage 2 Individual Indication Specific Cohorts   [ 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 ]

75.  Secondary:   AUC0-24 of Pictilisib on Cycle 1 Day 21 – Stage 2 Individual Indication Specific Cohorts   [ Time Frame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 21, Cycle 1 Day 22 ]

76.  Secondary:   t1/2 of Pictilisib on Cycle 1 Day 21 – Stage 2 Individual Indication Specific Cohorts   [ 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 ]

77.  Secondary:   CL/F of Pictilisib on Cycle 1 Day 21 – Stage 2 Individual Indication Specific Cohorts   [ 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 ]

78.  Secondary:   Accumulation Ratio of Pictilisib on Cycle 1 Day 21 – Stage 2 Individual Indication Specific Cohorts   [ 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 ]

79.  Secondary:   Tmax of Cobimetinib on Cycle 1 Day 1 – Stage 2A Individual Indication Specific 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 ]

80.  Secondary:   Cmax of Cobimetinib on Cycle 1 Day 1 – Stage 2A Individual Indication Specific 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 ]

81.  Secondary:   AUC0-24 of Cobimetinib on Cycle 1 Day 1 – Stage 2A Individual Indication Specific Cohorts   [ Time Frame: Pr-C dose, 0.5, 2, 4, 6 hours Po-C dose on Cycle 1 Day 1, Cycle 1 Days 2 ]

82.  Secondary:   Tmax of Cobimetinib on Cycle 1 Day 18 – Stage 2A Individual Indication Specific 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 ]

83.  Secondary:   Cmax of Cobimetinib on Cycle 1 Day 18 – Stage 2A Individual Indication Specific 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 ]

84.  Secondary:   AUC0-24 of Cobimetinib on Cycle 1 Day 18 – Stage 2A Individual Indication Specific 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 ]

85.  Secondary:   t1/2 of Cobimetinib on Cycle 1 Day 18 – Stage 2A Individual Indication Specific 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 ]

86.  Secondary:   CL/F of Cobimetinib on Cycle 1 Day 18 – Stage 2A Individual Indication Specific 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 ]

87.  Secondary:   Accumulation Ratio of Cobimetinib on Cycle 1 Day 18 – Stage 2A Individual Indication Specific 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 ]

88.  Secondary:   Tmax of Pictilisib on Cycle 1 Day 1 – Stage 2A Individual Indication Specific 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 ]

89.  Secondary:   Cmax of Pictilisib on Cycle 1 Day 1 – Stage 2A Individual Indication Specific 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 ]

90.  Secondary:   AUC0-24 of Pictilisib on Cycle 1 Day 1 – Stage 2A Individual Indication Specific Cohorts   [ Time Frame: Pr-P dose, 0.5, 2, 4, 6 hours Po-P dose on Cycle 1 Day 1, Cycle 1 Days 2 ]

91.  Secondary:   Tmax of Pictilisib on Cycle 1 Day 18 – Stage 2A Individual Indication Specific 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 ]

92.  Secondary:   Cmax of Pictilisib on Cycle 1 Day 18 – Stage 2A Individual Indication Specific 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 ]

93.  Secondary:   AUC0-24 of Pictilisib on Cycle 1 Day 18 – Stage 2A Individual Indication Specific 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 ]

94.  Secondary:   t1/2 of Pictilisib on Cycle 1 Day 18 – Stage 2A Individual Indication Specific 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 ]

95.  Secondary:   CL/F of Pictilisib on Cycle 1 Day 18 – Stage 2A Individual Indication Specific 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 ]

96.  Secondary:   Accumulation Ratio of Pictilisib on Cycle 1 Day 18 – Stage 2A Individual Indication Specific 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 ]

97.  Secondary:   Number of Participants With Best Overall Response - Dose Escalation Stages 1, 1A and 1B   [ Time Frame: Up to 30 days after last dose (last dose = up to Cycle 15, cycle length = 28 days) ]

98.  Secondary:   Duration of Objective Response - Dose Escalation Stages 1, 1A and 1B   [ Time Frame: Up to 30 days after last dose (last dose = up to Cycle 15, cycle length = 28 days) ]

99.  Secondary:   Progression-Free Survival (PFS) - Dose Escalation Stages 1, 1A and 1B   [ Time Frame: Up to 30 days after last dose (last dose = up to Cycle 15, cycle length = 28 days) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Medical Communications
Organization: Hoffman-La Roche
phone: 800-821-8590
e-mail: genentech@druginfo.com



Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT00996892     History of Changes
Other Study ID Numbers: MEK4752g
GO01330 ( Other Identifier: Hoffmann-La Roche )
Study First Received: October 12, 2009
Results First Received: March 3, 2016
Last Updated: November 4, 2016