A Phase Ib/II Study of LEE011 in Combination With MEK162 in Patients With NRAS Mutant Melanoma
Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT01781572
Collaborator
(none)
102
17
2
56.7
6
0.1
Study Details
Study Description
Brief Summary
In the phase Ib, the primary purpose is to establish the maximum tolerated dose (MTD)(s)/recommended phase ll dose (RP2D) and schedule of LEE011 and MEK162 orally administered combination. Once the MTD(s)/RP2D have been determined for each tested schedule, additional patients will be enrolled in the phase II portion of the study at the RP2D on the chosen schedule in order to assess the anti-tumor activity of the combination in addition to continued evaluation of safety.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
102 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase Ib/II, Multicenter, Open Label, Study of LEE011 in Combination With MEK162 in Adult Patients With NRAS Mutant Melanoma
Study Start Date
:
Jun 1, 2013
Actual Primary Completion Date
:
Jan 15, 2018
Actual Study Completion Date
:
Feb 20, 2018
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Phase Ib The phase Ib is the dose escalation part where successive cohorts of 3-6 newly enrolled patients receiving various dose pairs considering the recommendation from an adaptive BLRM incorporating the EWOC principle until MTD(s)/RP2D is defined. If multiple alternate dosing schedules are explored in parallel, the allocation of patients will proceed in an alternating fashion. Approximately 40 patients are expected to be treated during the phase Ib part of the study. Dosing Schedule 1: MEK162 administered orally twice daily on a continuous dosing schedule. LEE011 administered orally once daily for 21 days followed by a 1 week break (28-day cycle). Dosing Schedule 2: MEK162 administered orally twice daily and LEE011 administered orally once daily for 3 weeks followed by a 1 week break (28-day cycle). Dosing Schedule 3: MEK162 administered orally twice daily and LEE011 administered once daily for 2 weeks followed by a 1 week break (21-day cycle). |
Drug: LEE011
LEE011 will be administered orally once daily
Drug: MEK162
MEK162 will be administered orally twice daily
|
| Experimental: Phase II The Phase II part will begin once the MTD(s)/RP2D have been determined in the Phase Ib in order to assess antitumor activity of the LEE011and MEK162 combination. Patients enrolled in the Phase II part of the study are required to have measurable disease. Approximately 40 patients will be treated in this part. Phase II part will begin at the RP2D on the chosen schedule in order to assess antitumor activity of the LEE011 and MEK162 combination. |
Drug: LEE011
LEE011 will be administered orally once daily
Drug: MEK162
MEK162 will be administered orally twice daily
|
Outcome Measures
Primary Outcome Measures
- Number of Dose Limiting Toxicities (Phase Ib) [first 28 days of treatment]
To estimate the maximum tolerate doses (MTDs) and/or identify the RP2D and schedule of LEE011 and MEK162 combination. A dose-limiting toxicity (DLT) was defined as an AE or clinically significant abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurred within the first cycle of treatment with ribociclib and binimetinib.
- Objective Response Rate (ORR) (Phase II) [Approximately 12 months after the FPFV]
ORR is the proportion of patients with best overall response of complete response (CR) or partial response (PR) by month 2 assessed according to RECIST 1.1 criteria. ORR is done to describe the anti-tumor activity of LEE011 and MEK162 combination. The primary analysis of the ORR was based on the Investigator's assessment of overall lesion responses per RECIST 1.1.
Secondary Outcome Measures
- Plasma Concentration-time Profile (AUCtau) of LEE011 (Phase Ib) [Cycle 1 Day 1]
To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
- Plasma Concentration-time Profile (AUCtau) of MEK162 (Phase Ib) [Cycle 1 Day 1]
To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
- Plasma Concentration-time Profile (AUCtau,ss) of LEE011 (Phase Ib) [For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14]
To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
- Plasma Concentration-time Profile (AUCtau,ss) of MEK162 (Phase Ib) [For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14]
To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
- Plasma Concentration-time Profile (Cmin,ss) of LEE011 (Phase Ib) [For the 28-day schedule the steady-state parameter time frame was predose on Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was predose on Cycle 1 Day 14]
To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
- Plasma Concentration-time Profile (Cmin,ss) of MEK162 (Phase Ib) [For the 28-day schedule the steady-state parameter time frame was predose on Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was predose on Cycle 1 Day 14]
To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
- Plasma Concentration-time Profile (Cmax) of LEE011 (Phase Ib) [Cycle 1 Day 1]
To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
- Plasma Concentration-time Profile (Cmax) of MEK162 (Phase Ib) [Cycle 1 Day 1]
To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
- Plasma Concentration-time Profile (Cmax,ss) of LEE011 (Phase Ib) [For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14]
To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
- Plasma Concentration-time Profile (Cmax,ss) of MEK162 (Phase Ib) [For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14]
To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
- Plasma Concentration-time Profile (Tmax) of LEE011 (Phase Ib) [Cycle 1 Day 1]
To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
- Plasma Concentration-time Profile (Tmax) of MEK162 (Phase Ib) [Cycle 1 Day 1]
To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
- Plasma Concentration-time Profile (Tmax,ss) of LEE011 (Phase Ib) [For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14]
To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
- Plasma Concentration-time Profile (Tmax,ss) of MEK162 (Phase Ib) [For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14]
To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
- Plasma Concentration-time Profile (Accumulation Ratio, Racc_AUC) of LEE011 (Phase Ib) [For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14]
To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
- Plasma Concentration-time Profile (Accumulation Ratio, Racc_AUC) of MEK162 (Phase Ib) [For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14]
To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
- Plasma Concentration-time Profile (T1/2,ss) of LEE011 (Phase Ib) [For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14]
To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
- Plasma Concentration-time Profile (T1/2,ss) of MEK162 (Phase Ib) [For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14]
To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
- Plasma Concentration-time Profile (CL/F) of LEE011 (Phase Ib) [Cycle 1 Day 1]
To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib).
- Plasma Concentration-time Profile (CL/F) of MEK162 (Phase Ib) [Cycle 1 Day 1]
To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib).
- Number of Participants With Adverse Drug Reactions [Approximately 12 months after FPFV]
Safety and tolerability will be characterized through the incidence and severity of adverse drug reactions, serious adverse drug reactions, changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), dose interruptions, dose reduction and dose intensity.
- Duration of Response (DoR) - Phase 2 [Approximately 12 months after the FPFV]
To assess clinical safety as per RECIST 1.1. Evaluation will occur continuously throughout the trial until progression, or death due to underlying cancer. Please note: As clinicaltrials.gov only allows numerical data entry, the value of 999 indicates "not estimable" for confidence interval.
- Time to Progression (TTP) - Phase 2 [Approximately 12 months after the FPFV]
To assess clinical safety as per RECIST 1.1. Evaluation will occur continuously throughout the trial until progression, or death due to underlying cancer.
- Progression Free Survival (PFS) - Phase 1b and Phase 2 [Approximately 12 months after the FPFV]
To assess clinical safety as per RECIST 1.1. Evaluation will occur continuously throughout the trial until progression, or death due to underlying cancer. In the Phase 1b part, patients were combined for purposes of PFS analyses based on schedule received, since too few patients received any individual dose level to allow for valid PFS estimates within the respective dose levels. This is how the data were analyses and presented for the clinical study report.
- Overall Survival (OS) - Phase ll [Approximately 12 months after the FPFV]
To assess clinical safety as per RECIST 1.1. Evaluation will occur continuously throughout the trial until progression, or death due to underlying cancer.
- Best Overall Response (BOR) - Phase II [Approximately 12 months after the FPFV]
To assess clinical safety according to RECIST 1.1. Evaluation will occur continuously throughout the trial until progression, or death due to underlying cancer.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1.
-
Patients enrolled into phase Ib may be enrolled with evaluable disease only. Patients enrolled into the phase II expansion must have at least one measurable lesion as defined by RECIST 1.1 criteria for solid tumors.
-
Patients must have adequate organ function, as defined by the following parameter
-
Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L.
-
Hemoglobin (Hgb) ≥ 9 g/dL.
-
Platelets ≥ 75 x 109/L without transfusions within 21 days before 1st treatment.
-
PT/INR and aPTT ≤ 1.5 ULN.
-
Serum creatinine ≤1.5 ULN.
-
Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN).
-
AST and ALT ≤ 3 x ULN, except in patients with tumor involvement of the liver who must have AST and ALT ≤ 5 x ULN.
Exclusion Criteria:
-
Presence of any brain metastases detected by MRI or CT with i.v. contrast of the brain at screening.
-
Uncontrolled arterial hypertension despite medical treatment
-
Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
-
Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition scan (MUGA) or echocardiogram (ECHO).
-
Congenital long QT syndrome or family history of unexpected sudden cardiac death.
-
QTcF corrected with Frederica's or Bazett's formula QTcB >450 ms for males and
470 ms for females on screening ECG.
-
Angina pectoris ≤ 3 months prior to starting study drug
-
Acute myocardial infarction ≤ 3 months prior to starting study drug
-
Clinically significant resting bradycardia
-
History or presence of ventricular tachyarrhythmia
-
Unstable atrial fibrillation (ventricular response >100 bpm)
-
Complete left bundle branch block
-
Right bundle branch block and left anterior hemi block (bifascicular block)
-
Obligate use of a cardiac pacemaker or implantable cardioverter defibrillator
-
Any other clinically significant heart disease
-
Patients who are currently receiving treatment with agents that are known to cause QTc prolongation in humans.
-
Patients who have neuromuscular disorders that are associated with elevated CK (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy) or elevated baseline CK levels (≥ Grade 2)
-
Patients who are currently receiving treatment with agents that are metabolized predominantly through CYP3A4 and that have a narrow therapeutic window.
-
Patients with concurrent severe and/or uncontrolled concurrent medical conditions that could compromise participation in the study (i.e. uncontrolled diabetes mellitus, clinically significant pulmonary disease, clinically significant neurological disorder, active or uncontrolled infection).
-
History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes).
Other protocol related inclusion/exclusion criteria may apply.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of California, Dept of Oncology | San Francisco | California | United States | 94101 |
| 2 | California Pacific Medical Center Onc Dept | San Francisco | California | United States | 94120-7999 |
| 3 | Karmanos Cancer Institute Dept of Oncology | Detroit | Michigan | United States | 48201 |
| 4 | Memorial Sloan Kettering Cancer Center Dept Oncology | New York | New York | United States | 10021 |
| 5 | Columbia University Medical Center- New York Presbyterian Onc Dept. | New York | New York | United States | 10032 |
| 6 | Vanderbilt University Medical Center SC - Dept of Oncology . | Nashville | Tennessee | United States | 37232 |
| 7 | University of Texas/MD Anderson Cancer Center Dept of Onc. | Houston | Texas | United States | 77030-4009 |
| 8 | Pfizer Investigative Site 1003 | North Sydney | New South Wales | Australia | 2060 |
| 9 | Pfizer Investigative Site 1002 | Westmead | New South Wales | Australia | 2145 |
| 10 | Pfizer Investigator Site 1001 | East Melbourne | Victoria | Australia | |
| 11 | Pfizer Investigative Site 1050 | Essen | Germany | 45147 | |
| 12 | Pfizer Investigative Site 1053 | Gera | Germany | 07548 | |
| 13 | Pfizer Investigative Site 1052 | Hannover | Germany | 30625 | |
| 14 | Pfizer Investigative Site 1051 | Muenchen | Germany | 80336 | |
| 15 | Pfizer Investigative Site 1101 | Napoli | Italy | 80131 | |
| 16 | Pfizer Investigative Site 1151 | Utrecht | The Netherlands | Netherlands | 3508 GA |
| 17 | Pfizer Investigative Site 1150 | Nijmegen | Netherlands | 6525 GA |
Sponsors and Collaborators
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT01781572
Other Study ID Numbers:
- CMEK162X2114
- C4211005
First Posted:
Feb 1, 2013
Last Update Posted:
Dec 7, 2020
Last Verified:
Nov 1, 2020
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Upon study entry, all patients were required to provide either an archival tumor biopsy with the corresponding pathology report or a newly obtained tumor biopsy. Both parts of the study were limited to patients aged 18 or older with metastatic or locally advanced NRAS-mutant melanoma. |
|---|---|
| Pre-assignment Detail | Screening details: Screening assessments were performed within 14 days prior to the first dose of ribociclib and binimetinib except for the pretreatment tumor biopsy, which was performed within 28 days before dosing. A total of 23 patients were screened but not enrolled. |
| Arm/Group Title | Phase 1b 28-Day Schedule | Phase 1b 21-Day Schedule | Phase 2 (Dose-expansion Phase) |
|---|---|---|---|
| Arm/Group Description | A combined total of 61 patients were treated in the 28-day (n=29) and 21-day (n=32) treatment cycles, and all patients discontinued treatment. The starting dose in the 28-day schedule was binimetinib 45 mg BID + ribociclib 200 mg QD. 28-Day Schedule: ribociclib was taken QD for 21 consecutive days followed by a 7-day planned break. Binimetinib was taken BID on a continuous dosing schedule. | A combined total of 61 patients were treated in the 28-day (n=29) and 21-day (n=32) treatment cycles, and all patients discontinued treatment. The starting dose in the 21-day schedule was binimetinib 30 mg BID + ribociclib 200 mg QD. 21-Day Schedule: ribociclib QD and binimetinib BID were taken QD for 14 consecutive days followed by a 7-day planned break. | The dose-expansion phase was initiated with a newly recruited group of patients. A total of 41 patients were treated, and all patients (100%) discontinued treatment. Based on the recommendations of the dose-escalation meetings between the Sponsor and the Investigators, the RP2D and schedule for the combination of binimetinib and ribociclib to be used for the dose-expansion phase of the study was binimetinib 45 mg BID + ribociclib 200 mg QD on the 28-day schedule. |
| Period Title: MEK162 45mg BID+LEE011 200mg | |||
| STARTED | 16 | 6 | 41 |
| COMPLETED | 0 | 0 | 0 |
| NOT COMPLETED | 16 | 6 | 41 |
| Period Title: MEK162 45mg BID+LEE011 200mg | |||
| STARTED | 3 | 0 | 0 |
| COMPLETED | 0 | 0 | 0 |
| NOT COMPLETED | 3 | 0 | 0 |
| Period Title: MEK162 45mg BID+LEE011 200mg | |||
| STARTED | 4 | 2 | 0 |
| COMPLETED | 0 | 0 | 0 |
| NOT COMPLETED | 4 | 2 | 0 |
| Period Title: MEK162 45mg BID+LEE011 200mg | |||
| STARTED | 6 | 4 | 0 |
| COMPLETED | 0 | 0 | 0 |
| NOT COMPLETED | 6 | 4 | 0 |
| Period Title: MEK162 45mg BID+LEE011 200mg | |||
| STARTED | 0 | 5 | 0 |
| COMPLETED | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 5 | 0 |
| Period Title: MEK162 45mg BID+LEE011 200mg | |||
| STARTED | 0 | 9 | 0 |
| COMPLETED | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 9 | 0 |
| Period Title: MEK162 45mg BID+LEE011 200mg | |||
| STARTED | 0 | 6 | 0 |
| COMPLETED | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 6 | 0 |
Baseline Characteristics
| Arm/Group Title | Phase 1b 28-Day MEK162 45mg + LEE011 200mg | Phase 1b 28-Day MEK162 45mg+LEE011 250mg | Phase 1b 28-Day MEK162 30mg+LEE011 300mg | Phase 1b 28-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 30mg+LEE011 200mg | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | Phase 1b 21-Day MEK162 45mg+LEE011 600mg | Phase 2: MEK162 45mg+LEE011 200mg | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | MEK162 45mg + LEE011 200mg | MEK162 45mg+LEE011 250mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 30mg+LEE011 200mg | MEK162 45mg+LEE011 200mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 600mg | MEK162 45mg+LEE011 200mg | Total of all reporting groups |
| Overall Participants | 16 | 3 | 4 | 6 | 5 | 6 | 2 | 4 | 9 | 6 | 41 | 102 |
| Age (Count of Participants) | ||||||||||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
9
56.3%
|
2
66.7%
|
2
50%
|
4
66.7%
|
3
60%
|
3
50%
|
1
50%
|
2
50%
|
4
44.4%
|
5
83.3%
|
19
46.3%
|
54
52.9%
|
| >=65 years |
7
43.8%
|
1
33.3%
|
2
50%
|
2
33.3%
|
2
40%
|
3
50%
|
1
50%
|
2
50%
|
5
55.6%
|
1
16.7%
|
22
53.7%
|
48
47.1%
|
| Age (years) [Median (Standard Deviation) ] | ||||||||||||
| Median (Standard Deviation) [years] |
62
(14.51)
|
57
(9.02)
|
61.5
(21.30)
|
56
(15.04)
|
63.0
(7.50)
|
62.5
(12.687)
|
55.0
(18.38)
|
63.5
(19.48)
|
67.0
(8.59)
|
58.5
(5.56)
|
65
(12.35)
|
61
(12.72)
|
| Sex: Female, Male (Count of Participants) | ||||||||||||
| Female |
8
50%
|
0
0%
|
3
75%
|
1
16.7%
|
2
40%
|
3
50%
|
1
50%
|
2
50%
|
1
11.1%
|
5
83.3%
|
15
36.6%
|
41
40.2%
|
| Male |
8
50%
|
3
100%
|
1
25%
|
5
83.3%
|
3
60%
|
3
50%
|
1
50%
|
2
50%
|
8
88.9%
|
1
16.7%
|
26
63.4%
|
61
59.8%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||||||||||
| Caucasian |
16
100%
|
3
100%
|
4
100%
|
6
100%
|
5
100%
|
6
100%
|
1
50%
|
4
100%
|
9
100%
|
6
100%
|
40
97.6%
|
100
98%
|
| Other |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
50%
|
0
0%
|
0
0%
|
0
0%
|
1
2.4%
|
2
2%
|
| Weight (kilograms) [Mean (Standard Deviation) ] | ||||||||||||
| Mean (Standard Deviation) [kilograms] |
82.57
(15.014)
|
91.47
(20.093)
|
71.30
(12.631)
|
97.48
(35.464)
|
73.66
(8.104)
|
85.20
(20.733)
|
80.80
(15.274)
|
97.20
(24.554)
|
92.41
(20.709)
|
62.95
(6.111)
|
79.63
(17.334)
|
83.69
(20.621)
|
| Body mass index ((kg)/m^2) [Mean (Standard Deviation) ] | ||||||||||||
| Mean (Standard Deviation) [(kg)/m^2] |
28.57
(5.136)
|
26.84
(5.332)
|
25.95
(3.347)
|
30.38
(9.733)
|
23.85
(2.451)
|
27.80
(6.185)
|
27.92
(7.526)
|
31.71
(5.305)
|
28.08
(6.594)
|
23.50
(3.293)
|
26.69
(5.014)
|
27.34
(5.841)
|
| ECOG performance status (Count of Participants) | ||||||||||||
| 0-Without restriction |
10
62.5%
|
2
66.7%
|
1
25%
|
2
33.3%
|
3
60%
|
5
83.3%
|
2
100%
|
2
50%
|
5
55.6%
|
5
83.3%
|
28
68.3%
|
65
63.7%
|
| 1-Restricted in physically strenuous activity |
5
31.3%
|
0
0%
|
3
75%
|
4
66.7%
|
2
40%
|
1
16.7%
|
0
0%
|
2
50%
|
4
44.4%
|
1
16.7%
|
13
31.7%
|
35
34.3%
|
| 2-Ambulatory and capable of all selfcare |
1
6.3%
|
1
33.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
2%
|
Outcome Measures
| Title | Number of Dose Limiting Toxicities (Phase Ib) |
|---|---|
| Description | To estimate the maximum tolerate doses (MTDs) and/or identify the RP2D and schedule of LEE011 and MEK162 combination. A dose-limiting toxicity (DLT) was defined as an AE or clinically significant abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurred within the first cycle of treatment with ribociclib and binimetinib. |
| Time Frame | first 28 days of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis is comprised of the dose-determining set, which is all patients from the safety set who either met the minimum exposure criterion below and had sufficient safety evaluations during Cycle 1 or discontinued earlier due to DLT during Cycle 1. |
| Arm/Group Title | Phase 1b 28-Day MEK162 45mg + LEE011 200mg | Phase 1b 28-Day MEK162 45mg+LEE011 250mg | Phase 1b 28-Day MEK162 30mg+LEE011 300mg | Phase 1b 28-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 30mg+LEE011 200mg | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | Phase 1b 21-Day MEK162 45mg+LEE011 600mg |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | MEK162 45mg + LEE011 200mg | MEK162 45mg+LEE011 250mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 30mg+LEE011 200mg | MEK162 45mg+LEE011 200mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 600mg |
| Measure Participants | 16 | 3 | 4 | 6 | 5 | 6 | 2 | 4 | 9 | 6 |
| Number [occurrence] |
2
|
0
|
1
|
3
|
0
|
1
|
0
|
1
|
2
|
0
|
| Title | Objective Response Rate (ORR) (Phase II) |
|---|---|
| Description | ORR is the proportion of patients with best overall response of complete response (CR) or partial response (PR) by month 2 assessed according to RECIST 1.1 criteria. ORR is done to describe the anti-tumor activity of LEE011 and MEK162 combination. The primary analysis of the ORR was based on the Investigator's assessment of overall lesion responses per RECIST 1.1. |
| Time Frame | Approximately 12 months after the FPFV |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population consist of the Full Analysis Set, which included all patients who received at least one dose of binimetinib or ribociclib and was used for the analysis of all endpoints unless noted otherwise. |
| Arm/Group Title | Phase 2: Dose Expansion |
|---|---|
| Arm/Group Description | binimetinib 45 mg BID + ribociclib 200 mg QD (MEK 45mg + LEE 200mg) |
| Measure Participants | 41 |
| Count of Participants [Participants] |
8
50%
|
| Title | Plasma Concentration-time Profile (AUCtau) of LEE011 (Phase Ib) |
|---|---|
| Description | To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib). |
| Time Frame | Cycle 1 Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population consist of the pharmacokinetic analysis set (PAS) which consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug. |
| Arm/Group Title | Phase 1b 28-Day MEK162 45mg + LEE011 200mg | Phase 1b 28-Day MEK162 45mg+LEE011 250mg | Phase 1b 28-Day MEK162 30mg+LEE011 300mg | Phase 1b 28-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 30mg+LEE011 200mg | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | Phase 1b 21-Day MEK162 45mg+LEE011 600mg |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | MEK162 45mg + LEE011 200mg | MEK162 45mg+LEE011 250mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 30mg+LEE011 200mg | MEK162 45mg+LEE011 200mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 600mg |
| Measure Participants | 15 | 3 | 4 | 6 | 4 | 5 | 1 | 4 | 9 | 5 |
| Geometric Mean (Geometric Coefficient of Variation) [h*ng/ml] |
2120
(66.2)
|
3020
(99.4)
|
5280
(27.8)
|
3860
(42.3)
|
2340
(113)
|
2230
(74.5)
|
5020
(NA)
|
2960
(46.4)
|
5550
(50.3)
|
9840
(65.7)
|
| Title | Plasma Concentration-time Profile (AUCtau) of MEK162 (Phase Ib) |
|---|---|
| Description | To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib). |
| Time Frame | Cycle 1 Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis group is comprised of the pharmacokinetic analysis set (PAS) consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug. |
| Arm/Group Title | Phase 1b 28-Day MEK162 45mg + LEE011 200mg | Phase 1b 28-Day MEK162 45mg+LEE011 250mg | Phase 1b 28-Day MEK162 30mg+LEE011 300mg | Phase 1b 28-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 30mg+LEE011 200mg | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | Phase 1b 21-Day MEK162 45mg+LEE011 600mg |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | MEK162 45mg + LEE011 200mg | MEK162 45mg+LEE011 250mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 30mg+LEE011 200mg | MEK162 45mg+LEE011 200mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 600mg |
| Measure Participants | 6 | 1 | 1 | 1 | 2 | 3 | 2 | 1 | 2 | 1 |
| Geometric Mean (Geometric Coefficient of Variation) [h*ng/ml] |
1310
(36.8)
|
1070
(NA)
|
1640
(NA)
|
1240
(NA)
|
1610
(76)
|
1820
(82.1)
|
747
(31.8)
|
2740
(NA)
|
2110
(44.2)
|
4060
(NA)
|
| Title | Plasma Concentration-time Profile (AUCtau,ss) of LEE011 (Phase Ib) |
|---|---|
| Description | To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib). |
| Time Frame | For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis group is comprised of the pharmacokinetic analysis set (PAS) consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug. |
| Arm/Group Title | Phase 1b 28-Day MEK162 45mg + LEE011 200mg | Phase 1b 28-Day MEK162 45mg+LEE011 250mg | Phase 1b 28-Day MEK162 30mg+LEE011 300mg | Phase 1b 28-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 30mg+LEE011 200mg | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | Phase 1b 21-Day MEK162 45mg+LEE011 600mg |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | MEK162 45mg + LEE011 200mg | MEK162 45mg+LEE011 250mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 30mg+LEE011 200mg | MEK162 45mg+LEE011 200mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 600mg |
| Measure Participants | 13 | 1 | 1 | 2 | 4 | 5 | 2 | 2 | 5 | 5 |
| Geometric Mean (Geometric Coefficient of Variation) [h*ng/mL] |
3080
(63.2)
|
15000
(NA)
|
8650
(NA)
|
7050
(41.3)
|
4700
(28.9)
|
4370
(60.3)
|
7480
(2.89)
|
9570
(50.5)
|
11100
(29.1)
|
30700
(46.4)
|
| Title | Plasma Concentration-time Profile (AUCtau,ss) of MEK162 (Phase Ib) |
|---|---|
| Description | To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib). |
| Time Frame | For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis group is comprised of the pharmacokinetic analysis set (PAS) consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug. |
| Arm/Group Title | Phase 1b 28-Day MEK162 45mg + LEE011 200mg | Phase 1b 28-Day MEK162 45mg+LEE011 250mg | Phase 1b 28-Day MEK162 30mg+LEE011 300mg | Phase 1b 28-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 30mg+LEE011 200mg | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | Phase 1b 21-Day MEK162 45mg+LEE011 600mg |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | MEK162 45mg + LEE011 200mg | MEK162 45mg+LEE011 250mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 30mg+LEE011 200mg | MEK162 45mg+LEE011 200mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 600mg |
| Measure Participants | 11 | 1 | 0 | 4 | 4 | 4 | 2 | 3 | 4 | 5 |
| Geometric Mean (Geometric Coefficient of Variation) [h*ng/mL] |
2250
(37.7)
|
2450
(NA)
|
1540
(30.0)
|
2180
(12.1)
|
2980
(58.9)
|
1990
(22.2)
|
3680
(40.9)
|
2840
(57.5)
|
3340
(86.5)
|
| Title | Plasma Concentration-time Profile (Cmin,ss) of LEE011 (Phase Ib) |
|---|---|
| Description | To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib). |
| Time Frame | For the 28-day schedule the steady-state parameter time frame was predose on Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was predose on Cycle 1 Day 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population consist of the pharmacokinetic analysis set (PAS), which consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug. |
| Arm/Group Title | Phase 1b 28-Day MEK162 45mg + LEE011 200mg | Phase 1b 28-Day MEK162 45mg+LEE011 250mg | Phase 1b 28-Day MEK162 30mg+LEE011 300mg | Phase 1b 28-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 30mg+LEE011 200mg | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | Phase 1b 21-Day MEK162 45mg+LEE011 600mg |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | MEK162 45mg + LEE011 200mg | MEK162 45mg+LEE011 250mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 30mg+LEE011 200mg | MEK162 45mg+LEE011 200mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 600mg |
| Measure Participants | 14 | 2 | 1 | 4 | 4 | 5 | 2 | 2 | 5 | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [ng/mL] |
88.1
(56.3)
|
256
(79.8)
|
220
(NA)
|
113
(56.4)
|
117
(39.8)
|
97.6
(77.8)
|
140
(25.6)
|
216
(7.88)
|
264
(44.9)
|
570
(91.3)
|
| Title | Plasma Concentration-time Profile (Cmin,ss) of MEK162 (Phase Ib) |
|---|---|
| Description | To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib). |
| Time Frame | For the 28-day schedule the steady-state parameter time frame was predose on Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was predose on Cycle 1 Day 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population consist of the pharmacokinetic analysis set (PAS), which consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug. |
| Arm/Group Title | Phase 1b 28-Day MEK162 45mg + LEE011 200mg | Phase 1b 28-Day MEK162 45mg+LEE011 250mg | Phase 1b 28-Day MEK162 30mg+LEE011 300mg | Phase 1b 28-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 30mg+LEE011 200mg | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | Phase 1b 21-Day MEK162 45mg+LEE011 600mg |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | MEK162 45mg + LEE011 200mg | MEK162 45mg+LEE011 250mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 30mg+LEE011 200mg | MEK162 45mg+LEE011 200mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 600mg |
| Measure Participants | 11 | 2 | 1 | 3 | 4 | 4 | 1 | 3 | 4 | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [ng/mL] |
73.2
(75.4)
|
188
(73.9)
|
84.2
(NA)
|
43.9
(60.7)
|
103
(31.4)
|
90.4
(20.0)
|
123
(NA)
|
178
(38.1)
|
63.9
(94.3)
|
179
(98.3)
|
| Title | Plasma Concentration-time Profile (Cmax) of LEE011 (Phase Ib) |
|---|---|
| Description | To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib). |
| Time Frame | Cycle 1 Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis group is comprised of the pharmacokinetic analysis set (PAS) consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug. |
| Arm/Group Title | Phase 1b 28-Day MEK162 45mg + LEE011 200mg | Phase 1b 28-Day MEK162 45mg+LEE011 250mg | Phase 1b 28-Day MEK162 30mg+LEE011 300mg | Phase 1b 28-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 30mg+LEE011 200mg | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | Phase 1b 21-Day MEK162 45mg+LEE011 600mg |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | MEK162 45mg + LEE011 200mg | MEK162 45mg+LEE011 250mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 30mg+LEE011 200mg | MEK162 45mg+LEE011 200mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 600mg |
| Measure Participants | 15 | 3 | 4 | 6 | 4 | 5 | 1 | 4 | 9 | 5 |
| Geometric Mean (Geometric Coefficient of Variation) [ng/mL] |
217
(90.5)
|
271
(87.4)
|
555
(44.4)
|
374
(47.9)
|
236
(143)
|
229
(86.0)
|
368
(NA)
|
307
(33.0)
|
506
(65.6)
|
1030
(54.1)
|
| Title | Plasma Concentration-time Profile (Cmax) of MEK162 (Phase Ib) |
|---|---|
| Description | To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib). |
| Time Frame | Cycle 1 Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis group is comprised of the pharmacokinetic analysis set (PAS) consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug. |
| Arm/Group Title | Phase 1b 28-Day MEK162 45mg + LEE011 200mg | Phase 1b 28-Day MEK162 45mg+LEE011 250mg | Phase 1b 28-Day MEK162 30mg+LEE011 300mg | Phase 1b 28-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 30mg+LEE011 200mg | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | Phase 1b 21-Day MEK162 45mg+LEE011 600mg |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | MEK162 45mg + LEE011 200mg | MEK162 45mg+LEE011 250mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 30mg+LEE011 200mg | MEK162 45mg+LEE011 200mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 600mg |
| Measure Participants | 15 | 3 | 3 | 6 | 5 | 6 | 2 | 4 | 9 | 5 |
| Geometric Mean (Geometric Coefficient of Variation) [ng/mL] |
315
(55.7)
|
296
(48.4)
|
247
(59.7)
|
231
(47.3)
|
234
(73.9)
|
453
(67.1)
|
163
(47.8)
|
396
(52.7)
|
385
(50.3)
|
402
(69.8)
|
| Title | Plasma Concentration-time Profile (Cmax,ss) of LEE011 (Phase Ib) |
|---|---|
| Description | To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib). |
| Time Frame | For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis group is comprised of the pharmacokinetic analysis set (PAS) consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug. |
| Arm/Group Title | Phase 1b 28-Day MEK162 45mg + LEE011 200mg | Phase 1b 28-Day MEK162 45mg+LEE011 250mg | Phase 1b 28-Day MEK162 30mg+LEE011 300mg | Phase 1b 28-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 30mg+LEE011 200mg | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | Phase 1b 21-Day MEK162 45mg+LEE011 600mg |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | MEK162 45mg + LEE011 200mg | MEK162 45mg+LEE011 250mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 30mg+LEE011 200mg | MEK162 45mg+LEE011 200mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 600mg |
| Measure Participants | 14 | 2 | 1 | 4 | 5 | 5 | 2 | 2 | 5 | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [ng/mL] |
220
(76.5)
|
343
(150)
|
220
(NA)
|
530
(30.6)
|
373
(62.4)
|
341
(69.0)
|
543
(11.9)
|
747
(33.0)
|
727
(34.7)
|
1910
(38.5)
|
| Title | Plasma Concentration-time Profile (Cmax,ss) of MEK162 (Phase Ib) |
|---|---|
| Description | To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib). |
| Time Frame | For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis group is comprised of the pharmacokinetic analysis set (PAS) consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug. |
| Arm/Group Title | Phase 1b 28-Day MEK162 45mg + LEE011 200mg | Phase 1b 28-Day MEK162 45mg+LEE011 250mg | Phase 1b 28-Day MEK162 30mg+LEE011 300mg | Phase 1b 28-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 30mg+LEE011 200mg | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | Phase 1b 21-Day MEK162 45mg+LEE011 600mg |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | MEK162 45mg + LEE011 200mg | MEK162 45mg+LEE011 250mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 30mg+LEE011 200mg | MEK162 45mg+LEE011 200mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 600mg |
| Measure Participants | 11 | 2 | 0 | 4 | 5 | 4 | 2 | 3 | 4 | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [ng/mL] |
441
(52.6)
|
309
(1.60)
|
284
(14.5)
|
376
(18.0)
|
444
(36.6)
|
367
(31.5)
|
590
(12.3)
|
452
(59.2)
|
471
(75.6)
|
| Title | Plasma Concentration-time Profile (Tmax) of LEE011 (Phase Ib) |
|---|---|
| Description | To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib). |
| Time Frame | Cycle 1 Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population consist of the pharmacokinetic analysis set (PAS), which consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug. |
| Arm/Group Title | Phase 1b 28-Day MEK162 45mg + LEE011 200mg | Phase 1b 28-Day MEK162 45mg+LEE011 250mg | Phase 1b 28-Day MEK162 30mg+LEE011 300mg | Phase 1b 28-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 30mg+LEE011 200mg | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | Phase 1b 21-Day MEK162 45mg+LEE011 600mg |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | MEK162 45mg + LEE011 200mg | MEK162 45mg+LEE011 250mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 30mg+LEE011 200mg | MEK162 45mg+LEE011 200mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 600mg |
| Measure Participants | 15 | 3 | 4 | 6 | 4 | 5 | 1 | 4 | 9 | 5 |
| Median (Full Range) [h] |
2.12
|
3.75
|
2.98
|
1.50
|
2.98
|
1.12
|
4.22
|
1.50
|
2.13
|
2.03
|
| Title | Plasma Concentration-time Profile (Tmax) of MEK162 (Phase Ib) |
|---|---|
| Description | To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib). |
| Time Frame | Cycle 1 Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population consist of the pharmacokinetic analysis set (PAS), which consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug. |
| Arm/Group Title | Phase 1b 28-Day MEK162 45mg + LEE011 200mg | Phase 1b 28-Day MEK162 45mg+LEE011 250mg | Phase 1b 28-Day MEK162 30mg+LEE011 300mg | Phase 1b 28-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 30mg+LEE011 200mg | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | Phase 1b 21-Day MEK162 45mg+LEE011 600mg |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | MEK162 45mg + LEE011 200mg | MEK162 45mg+LEE011 250mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 30mg+LEE011 200mg | MEK162 45mg+LEE011 200mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 600mg |
| Measure Participants | 15 | 3 | 3 | 6 | 5 | 6 | 2 | 4 | 9 | 5 |
| Median (Full Range) [h] |
1.08
|
2.05
|
1.02
|
2.00
|
1.98
|
1.11
|
0.76
|
2.00
|
2.17
|
1.17
|
| Title | Plasma Concentration-time Profile (Tmax,ss) of LEE011 (Phase Ib) |
|---|---|
| Description | To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib). |
| Time Frame | For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population consist of the pharmacokinetic analysis set (PAS), which consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug. |
| Arm/Group Title | Phase 1b 28-Day MEK162 45mg + LEE011 200mg | Phase 1b 28-Day MEK162 45mg+LEE011 250mg | Phase 1b 28-Day MEK162 30mg+LEE011 300mg | Phase 1b 28-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 30mg+LEE011 200mg | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | Phase 1b 21-Day MEK162 45mg+LEE011 600mg |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | MEK162 45mg + LEE011 200mg | MEK162 45mg+LEE011 250mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 30mg+LEE011 200mg | MEK162 45mg+LEE011 200mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 600mg |
| Measure Participants | 14 | 2 | 1 | 4 | 5 | 5 | 2 | 2 | 5 | 6 |
| Median (Full Range) [h] |
2.25
|
5.90
|
23.93
|
2.99
|
4.00
|
1.87
|
2.03
|
4.05
|
3.92
|
1.93
|
| Title | Plasma Concentration-time Profile (Tmax,ss) of MEK162 (Phase Ib) |
|---|---|
| Description | To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib). |
| Time Frame | For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population consist of the pharmacokinetic analysis set (PAS), which consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug. |
| Arm/Group Title | Phase 1b 28-Day MEK162 45mg + LEE011 200mg | Phase 1b 28-Day MEK162 45mg+LEE011 250mg | Phase 1b 28-Day MEK162 30mg+LEE011 300mg | Phase 1b 28-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 30mg+LEE011 200mg | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | Phase 1b 21-Day MEK162 45mg+LEE011 600mg |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | MEK162 45mg + LEE011 200mg | MEK162 45mg+LEE011 250mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 30mg+LEE011 200mg | MEK162 45mg+LEE011 200mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 600mg |
| Measure Participants | 11 | 2 | 0 | 4 | 5 | 4 | 2 | 3 | 4 | 6 |
| Median (Full Range) [h] |
1.00
|
3.03
|
2.31
|
1.00
|
1.96
|
1.49
|
2.02
|
1.92
|
1.49
|
| Title | Plasma Concentration-time Profile (Accumulation Ratio, Racc_AUC) of LEE011 (Phase Ib) |
|---|---|
| Description | To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib). |
| Time Frame | For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population consist of the pharmacokinetic analysis set (PAS), which consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug. |
| Arm/Group Title | Phase 1b 28-Day MEK162 45mg + LEE011 200mg | Phase 1b 28-Day MEK162 45mg+LEE011 250mg | Phase 1b 28-Day MEK162 30mg+LEE011 300mg | Phase 1b 28-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 30mg+LEE011 200mg | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | Phase 1b 21-Day MEK162 45mg+LEE011 600mg |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | MEK162 45mg + LEE011 200mg | MEK162 45mg+LEE011 250mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 30mg+LEE011 200mg | MEK162 45mg+LEE011 200mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 600mg |
| Measure Participants | 13 | 1 | 1 | 4 | 4 | 5 | 2 | 2 | 5 | 5 |
| Geometric Mean (Geometric Coefficient of Variation) [(hr*ng/mL) / (hr*ng/mL)] |
1.51
(53.9)
|
2.52
(NA)
|
2.25
(NA)
|
2.29
(38.4)
|
2.89
(32.8)
|
2.28
(54.6)
|
3.29
(165)
|
3.50
(8.68)
|
1.97
(45.4)
|
3.95
(58.6)
|
| Title | Plasma Concentration-time Profile (Accumulation Ratio, Racc_AUC) of MEK162 (Phase Ib) |
|---|---|
| Description | To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib). |
| Time Frame | For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population consist of the pharmacokinetic analysis set (PAS), which consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug. |
| Arm/Group Title | Phase 1b 28-Day MEK162 45mg + LEE011 200mg | Phase 1b 28-Day MEK162 45mg+LEE011 250mg | Phase 1b 28-Day MEK162 30mg+LEE011 300mg | Phase 1b 28-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 30mg+LEE011 200mg | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | Phase 1b 21-Day MEK162 45mg+LEE011 600mg |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | MEK162 45mg + LEE011 200mg | MEK162 45mg+LEE011 250mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 30mg+LEE011 200mg | MEK162 45mg+LEE011 200mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 600mg |
| Measure Participants | 13 | 1 | 1 | 4 | 4 | 5 | 2 | 2 | 5 | 5 |
| Geometric Mean (Geometric Coefficient of Variation) [(hr*ng/mL) / (hr*ng/mL] |
2.53
(45.8)
|
7.59
(NA)
|
1.74
(NA)
|
3.39
(15.2)
|
4.47
(21.5)
|
2.26
(27.3)
|
3.14
(161)
|
3.48
(53.0)
|
2.09
(53.5)
|
3.06
(26.0)
|
| Title | Plasma Concentration-time Profile (T1/2,ss) of LEE011 (Phase Ib) |
|---|---|
| Description | To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib). |
| Time Frame | For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population consist of the pharmacokinetic analysis set (PAS), which consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug. |
| Arm/Group Title | Phase 1b 28-Day MEK162 45mg + LEE011 200mg | Phase 1b 28-Day MEK162 45mg+LEE011 250mg | Phase 1b 28-Day MEK162 30mg+LEE011 300mg | Phase 1b 28-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 30mg+LEE011 200mg | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | Phase 1b 21-Day MEK162 45mg+LEE011 600mg |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | MEK162 45mg + LEE011 200mg | MEK162 45mg+LEE011 250mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 30mg+LEE011 200mg | MEK162 45mg+LEE011 200mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 600mg |
| Measure Participants | 11 | 1 | 1 | 4 | 4 | 5 | 2 | 2 | 4 | 5 |
| Geometric Mean (Geometric Coefficient of Variation) [h] |
16.7
(83.6)
|
32.9
(NA)
|
28.2
(NA)
|
28.0
(54.7)
|
38.5
(44.4)
|
26.9
(82.0)
|
275
(64.5)
|
49.5
(10.3)
|
30.3
(17.6)
|
55.3
(73.1)
|
| Title | Plasma Concentration-time Profile (T1/2,ss) of MEK162 (Phase Ib) |
|---|---|
| Description | To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib). |
| Time Frame | For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population consist of the pharmacokinetic analysis set (PAS), which consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug. |
| Arm/Group Title | Phase 1b 28-Day MEK162 45mg + LEE011 200mg | Phase 1b 28-Day MEK162 45mg+LEE011 250mg | Phase 1b 28-Day MEK162 30mg+LEE011 300mg | Phase 1b 28-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 30mg+LEE011 200mg | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | Phase 1b 21-Day MEK162 45mg+LEE011 600mg |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | MEK162 45mg + LEE011 200mg | MEK162 45mg+LEE011 250mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 30mg+LEE011 200mg | MEK162 45mg+LEE011 200mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 600mg |
| Measure Participants | 11 | 2 | 0 | 4 | 4 | 4 | 2 | 3 | 4 | 5 |
| Geometric Mean (Geometric Coefficient of Variation) [h] |
8.17
(30.6)
|
7.38
(92.6)
|
6.33
(81.1)
|
15.0
(54.8)
|
5.21
(73.2)
|
15.4
(11.4)
|
8.95
(23.9)
|
8.73
(19.3)
|
12.0
(31.2)
|
| Title | Plasma Concentration-time Profile (CL/F) of LEE011 (Phase Ib) |
|---|---|
| Description | To Characterize the PK profiles of LEE011 as well as any other significant metabolites identified (Phase Ib). |
| Time Frame | Cycle 1 Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population consist of the pharmacokinetic analysis set (PAS), which consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug. |
| Arm/Group Title | Phase 1b 28-Day MEK162 45mg + LEE011 200mg | Phase 1b 28-Day MEK162 45mg+LEE011 250mg | Phase 1b 28-Day MEK162 30mg+LEE011 300mg | Phase 1b 28-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 30mg+LEE011 200mg | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | Phase 1b 21-Day MEK162 45mg+LEE011 600mg |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | MEK162 45mg + LEE011 200mg | MEK162 45mg+LEE011 250mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 30mg+LEE011 200mg | MEK162 45mg+LEE011 200mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 600mg |
| Measure Participants | 8 | 1 | 2 | 5 | 2 | 3 | 0 | 3 | 4 | 5 |
| Geometric Mean (Geometric Coefficient of Variation) [L/h] |
72.7
(75.4)
|
41.2
(NA)
|
39.2
(26.7)
|
67.6
(35.9)
|
34.3
(81.7)
|
57.2
(52.7)
|
93.9
(36.1)
|
78.4
(16.0)
|
48.7
(68.8)
|
| Title | Plasma Concentration-time Profile (CL/F) of MEK162 (Phase Ib) |
|---|---|
| Description | To Characterize the PK profiles of MEK162 as well as any other significant metabolites identified (Phase Ib). |
| Time Frame | Cycle 1 Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population consist of the pharmacokinetic analysis set (PAS), which consisted of all patients who had at least one blood sample providing evaluable PK data and received at least one dose of study drug. |
| Arm/Group Title | Phase 1b 28-Day MEK162 45mg + LEE011 200mg | Phase 1b 28-Day MEK162 45mg+LEE011 250mg | Phase 1b 28-Day MEK162 30mg+LEE011 300mg | Phase 1b 28-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 30mg+LEE011 200mg | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | Phase 1b 21-Day MEK162 45mg+LEE011 600mg |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | MEK162 45mg + LEE011 200mg | MEK162 45mg+LEE011 250mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 30mg+LEE011 200mg | MEK162 45mg+LEE011 200mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 600mg |
| Measure Participants | 6 | 1 | 1 | 1 | 2 | 3 | 2 | 1 | 2 | 1 |
| Geometric Mean (Geometric Coefficient of Variation) [L/h] |
32.5
(36.3)
|
35.9
(NA)
|
17.8
(NA)
|
35.5
(NA)
|
17.9
(80.7)
|
23.9
(83.6)
|
37.2
(23.0)
|
15.9
(NA)
|
20.8
(45.8)
|
10.2
(NA)
|
| Title | Number of Participants With Adverse Drug Reactions |
|---|---|
| Description | Safety and tolerability will be characterized through the incidence and severity of adverse drug reactions, serious adverse drug reactions, changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), dose interruptions, dose reduction and dose intensity. |
| Time Frame | Approximately 12 months after FPFV |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis group consists of the safety set, which included all patients who received at least 1 dose of ribociclib or binimetinib and had at least 1 postbaseline safety assessment. |
| Arm/Group Title | Phase 1b 28-Day MEK162 45mg + LEE011 200mg | Phase 1b 28-Day MEK162 45mg+LEE011 250mg | Phase 1b 28-Day MEK162 30mg+LEE011 300mg | Phase 1b 28-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 30mg+LEE011 200mg | Phase 1b 21-Day MEK162 45mg+LEE011 200mg | Phase 1b 21-Day MEK162 30mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 300mg | Phase 1b 21-Day MEK162 45mg+LEE011 450mg | Phase 1b 21-Day MEK162 45mg+LEE011 600mg | Phase 2: MEK162 45mg+LEE011 200mg |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | MEK162 45mg + LEE011 200mg | MEK162 45mg+LEE011 250mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 30mg+LEE011 200mg | MEK162 45mg+LEE011 200mg | MEK162 30mg+LEE011 300mg | MEK162 45mg+LEE011 300mg | MEK162 45mg+LEE011 450mg | MEK162 45mg+LEE011 600mg | MEK162 45mg+LEE011 200mg |
| Measure Participants | 16 | 3 | 4 | 6 | 5 | 6 | 2 | 4 | 9 | 6 | 41 |
| Count of Participants [Participants] |
16
100%
|
3
100%
|
4
100%
|
6
100%
|
5
100%
|
6
100%
|
2
100%
|
4
100%
|
9
100%
|
6
100%
|
41
100%
|
| Title | Duration of Response (DoR) - Phase 2 |
|---|---|
| Description | To assess clinical safety as per RECIST 1.1. Evaluation will occur continuously throughout the trial until progression, or death due to underlying cancer. Please note: As clinicaltrials.gov only allows numerical data entry, the value of 999 indicates "not estimable" for confidence interval. |
| Time Frame | Approximately 12 months after the FPFV |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population consist of the Full Analysis Set, which included all patients who received at least one dose of binimetinib or ribociclib and was used for the analysis of all endpoints unless noted otherwise. |
| Arm/Group Title | Phase 2: Dose Expansion |
|---|---|
| Arm/Group Description | The dose-expansion phase was initiated with a newly recruited group of patients. Binimetinib 45 mg BID + ribociclib 200 mg QD on 28-day schedule |
| Measure Participants | 41 |
| Median (95% Confidence Interval) [months] |
10.3
|
| Title | Time to Progression (TTP) - Phase 2 |
|---|---|
| Description | To assess clinical safety as per RECIST 1.1. Evaluation will occur continuously throughout the trial until progression, or death due to underlying cancer. |
| Time Frame | Approximately 12 months after the FPFV |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population consist of the Full Analysis Set, which included all patients who received at least one dose of binimetinib or ribociclib and was used for the analysis of all endpoints unless noted otherwise. |
| Arm/Group Title | Phase 2: Dose Expansion |
|---|---|
| Arm/Group Description | The dose-expansion phase was initiated with a newly recruited group of patients. Binimetinib 45 mg BID + ribociclib 200 mg QD on 28-day schedule |
| Measure Participants | 41 |
| Median (95% Confidence Interval) [months] |
3.7
|
| Title | Progression Free Survival (PFS) - Phase 1b and Phase 2 |
|---|---|
| Description | To assess clinical safety as per RECIST 1.1. Evaluation will occur continuously throughout the trial until progression, or death due to underlying cancer. In the Phase 1b part, patients were combined for purposes of PFS analyses based on schedule received, since too few patients received any individual dose level to allow for valid PFS estimates within the respective dose levels. This is how the data were analyses and presented for the clinical study report. |
| Time Frame | Approximately 12 months after the FPFV |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population consist of the Full Analysis Set, which included all patients who received at least one dose of binimetinib or ribociclib and was used for the analysis of all endpoints unless noted otherwise. |
| Arm/Group Title | Phase 1b 28-Day Schedule | Phase 1b 21-Day Schedule | Phase 2 (Dose-expansion Phase) |
|---|---|---|---|
| Arm/Group Description | A combined total of 61 patients were treated in the 28-day (n=29) and 21-day (n=32) treatment cycles, and all patients discontinued treatment. The starting dose in the 28-day schedule was binimetinib 45 mg BID + ribociclib 200 mg QD. 28-Day Schedule: ribociclib was taken QD for 21 consecutive days followed by a 7-day planned break. Binimetinib was taken BID on a continuous dosing schedule. | A combined total of 61 patients were treated in the 28-day (n=29) and 21-day (n=32) treatment cycles, and all patients discontinued treatment. The starting dose in the 21-day schedule was binimetinib 30 mg BID + ribociclib 200 mg QD. 21-Day Schedule: ribociclib QD and binimetinib BID were taken QD for 14 consecutive days followed by a 7-day planned break. | The dose-expansion phase was initiated with a newly recruited group of patients. A total of 41 patients were treated, and all patients (100%) discontinued treatment. Based on the recommendations of the dose-escalation meetings between the Sponsor and the Investigators, the RP2D and schedule for the combination of binimetinib and ribociclib to be used for the dose-expansion phase of the study was binimetinib 45 mg BID + ribociclib 200 mg QD on the 28-day schedule. |
| Measure Participants | 29 | 32 | 41 |
| Median (95% Confidence Interval) [months] |
6.7
|
4.1
|
3.7
|
| Title | Overall Survival (OS) - Phase ll |
|---|---|
| Description | To assess clinical safety as per RECIST 1.1. Evaluation will occur continuously throughout the trial until progression, or death due to underlying cancer. |
| Time Frame | Approximately 12 months after the FPFV |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population consist of the Full Analysis Set, which included all patients who received at least one dose of binimetinib or ribociclib and was used for the analysis of all endpoints unless noted otherwise. |
| Arm/Group Title | Phase 2: Dose Expansion |
|---|---|
| Arm/Group Description | The dose-expansion phase was initiated with a newly recruited group of patients. Binimetinib 45 mg BID + ribociclib 200 mg QD on 28-day schedule |
| Measure Participants | 41 |
| Median (95% Confidence Interval) [months] |
11.3
|
| Title | Best Overall Response (BOR) - Phase II |
|---|---|
| Description | To assess clinical safety according to RECIST 1.1. Evaluation will occur continuously throughout the trial until progression, or death due to underlying cancer. |
| Time Frame | Approximately 12 months after the FPFV |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population consist of the Full Analysis Set, which included all patients who received at least one dose of binimetinib or ribociclib and was used for the analysis of all endpoints unless noted otherwise. |
| Arm/Group Title | Phase 2: Dose Expansion |
|---|---|
| Arm/Group Description | The dose-expansion phase was initiated with a newly recruited group of patients. Binimetinib 45 mg BID + ribociclib 200 mg QD on 28-day schedule |
| Measure Participants | 41 |
| Complete Response |
0
0%
|
| Partial Response |
8
50%
|
| Stable Disease |
21
131.3%
|
| Progressive Disease |
6
37.5%
|
| Non-CR/Non-PD |
0
0%
|
| Unknown |
6
37.5%
|
Adverse Events
| Time Frame | Adverse Events (AE) were collected during the study, which began in June 2013 and concluded February 2018. After signing of the informed consent until 30 days after study treatment discontinuation. | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after patient's signed informed consent has been obtained. | |||||||||||||||||||||
| Arm/Group Title | Phase 1b - 28 Day MEK162 45mg+LEE011 200mg | Phase 1b - 28 Day MEK162 45mg+LEE011 250mg | Phase 1b - 28 Day MEK162 30mg+LEE011 300mg | Phase 1b - 28 Day MEK162 45mg+LEE011 300mg | Phase 1b - 21 Day MEK162 30mg+LEE011 200mg | Phase 1b - 21 Day MEK162 45mg+LEE011 200mg | Phase 1b - 21 Day MEK162 30mg+LEE011 300mg | Phase 1b - 21 Day MEK162 45mg+LEE011 300mg | Phase 1b - 21 Day MEK162 45mg+LEE011 450mg | Phase 1b - 21 Day MEK162 45mg+LEE011 600mg | Phase 2 - Dose Expansion Phase | |||||||||||
| Arm/Group Description | MEK162 45mg BID+LEE011 200mg QD | MEK162 45mg BID+LEE011 250mg QD | MEK162 30mg BID+LEE011 300mg QD | MEK162 45mg BID+LEE011 300mg QD | MEK162 30mg BID+LEE011 200mg QD | MEK162 45mg BID+LEE011 200mg QD | MEK162 30mg BID+LEE011 300mg QD | MEK162 45mg BID+LEE011 300mg QD | MEK162 45mg BID+LEE011 450mg QD | MEK162 45mg BID+LEE011 600mg QD | The dose-expansion phase was initiated with a newly recruited group of patients. Binimetinib 45 mg BID + ribociclib 200 mg QD on 28-day schedule | |||||||||||
All Cause Mortality |
||||||||||||||||||||||
| Phase 1b - 28 Day MEK162 45mg+LEE011 200mg | Phase 1b - 28 Day MEK162 45mg+LEE011 250mg | Phase 1b - 28 Day MEK162 30mg+LEE011 300mg | Phase 1b - 28 Day MEK162 45mg+LEE011 300mg | Phase 1b - 21 Day MEK162 30mg+LEE011 200mg | Phase 1b - 21 Day MEK162 45mg+LEE011 200mg | Phase 1b - 21 Day MEK162 30mg+LEE011 300mg | Phase 1b - 21 Day MEK162 45mg+LEE011 300mg | Phase 1b - 21 Day MEK162 45mg+LEE011 450mg | Phase 1b - 21 Day MEK162 45mg+LEE011 600mg | Phase 2 - Dose Expansion Phase | ||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/16 (18.8%) | 0/3 (0%) | 1/4 (25%) | 1/6 (16.7%) | 0/5 (0%) | 1/6 (16.7%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 1/6 (16.7%) | 23/41 (56.1%) | |||||||||||
Serious Adverse Events |
||||||||||||||||||||||
| Phase 1b - 28 Day MEK162 45mg+LEE011 200mg | Phase 1b - 28 Day MEK162 45mg+LEE011 250mg | Phase 1b - 28 Day MEK162 30mg+LEE011 300mg | Phase 1b - 28 Day MEK162 45mg+LEE011 300mg | Phase 1b - 21 Day MEK162 30mg+LEE011 200mg | Phase 1b - 21 Day MEK162 45mg+LEE011 200mg | Phase 1b - 21 Day MEK162 30mg+LEE011 300mg | Phase 1b - 21 Day MEK162 45mg+LEE011 300mg | Phase 1b - 21 Day MEK162 45mg+LEE011 450mg | Phase 1b - 21 Day MEK162 45mg+LEE011 600mg | Phase 2 - Dose Expansion Phase | ||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 8/16 (50%) | 2/3 (66.7%) | 2/4 (50%) | 4/6 (66.7%) | 2/5 (40%) | 3/6 (50%) | 1/2 (50%) | 3/4 (75%) | 3/9 (33.3%) | 2/6 (33.3%) | 22/41 (53.7%) | |||||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||||||
| Febrile neutropenia | 0/16 (0%) | 1/3 (33.3%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Anaemia | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 1/41 (2.4%) | |||||||||||
| Cardiac disorders | ||||||||||||||||||||||
| Cardio-respiratory arrest | 1/16 (6.3%) | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Atrial fibrillation | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Eye disorders | ||||||||||||||||||||||
| Retinal detachment | 1/16 (6.3%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Gastrointestinal disorders | ||||||||||||||||||||||
| Small intestinal | 1/16 (6.3%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Nausea | 1/16 (6.3%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 1/2 (50%) | 0/4 (0%) | 1/9 (11.1%) | 0/6 (0%) | 1/41 (2.4%) | |||||||||||
| Vomiting | 1/16 (6.3%) | 1/3 (33.3%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 1/9 (11.1%) | 0/6 (0%) | 2/41 (4.9%) | |||||||||||
| Constipation | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 0/5 (0%) | 1/6 (16.7%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Rectal haemorrhage | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 1/4 (25%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Rectal obstruction | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 1/4 (25%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Intestinal haemorrhage | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 1/41 (2.4%) | |||||||||||
| Subileus | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 1/41 (2.4%) | |||||||||||
| Colitis | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 1/41 (2.4%) | |||||||||||
| Large intestine perforation | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 1/41 (2.4%) | |||||||||||
| Chills | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 1/41 (2.4%) | |||||||||||
| Gastrointestinal haemorrhage | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 1/41 (2.4%) | |||||||||||
| General disorders | ||||||||||||||||||||||
| Pain | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Fatigue | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 1/2 (50%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Face oedema | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 1/4 (25%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Hepatobiliary disorders | ||||||||||||||||||||||
| Hepatitis | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 1/6 (16.7%) | 0/41 (0%) | |||||||||||
| Cholangitis | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 1/41 (2.4%) | |||||||||||
| Infections and infestations | ||||||||||||||||||||||
| Gastroenteritis | 0/16 (0%) | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Sepsis | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 1/41 (2.4%) | |||||||||||
| Peritonitis | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Pneumonia | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 2/6 (33.3%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Upper respiratory tract infection | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 1/6 (16.7%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Cellulitis | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 2/6 (33.3%) | 0/2 (0%) | 1/4 (25%) | 0/9 (0%) | 0/6 (0%) | 2/41 (4.9%) | |||||||||||
| Lung infection | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 1/9 (11.1%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Staphylococcal bacteraemia | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 1/41 (2.4%) | |||||||||||
| Erysipelas | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 2/41 (4.9%) | |||||||||||
| Bacteraemia | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 1/41 (2.4%) | |||||||||||
| Infection | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 1/41 (2.4%) | |||||||||||
| Herpes zoster | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 1/41 (2.4%) | |||||||||||
| Investigations | ||||||||||||||||||||||
| Blood creatine phosphokinase | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Neutrophil | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 1/9 (11.1%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Aspartate aminotransferase increased | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 1/6 (16.7%) | 0/41 (0%) | |||||||||||
| Metabolism and nutrition disorders | ||||||||||||||||||||||
| Hypervolaemia | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Diabetes mellitus | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 1/41 (2.4%) | |||||||||||
| Hypokalaemia | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 1/41 (2.4%) | |||||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||
| Muscular weakness | 1/16 (6.3%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||||
| Tumour haemorrhage | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 2/5 (40%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Intracranial tumour haemorrhage | 0/16 (0%) | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 4/41 (9.8%) | |||||||||||
| Tumour pain | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 1/4 (25%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Nervous system disorders | ||||||||||||||||||||||
| Pyrexia | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 2/4 (50%) | 1/9 (11.1%) | 1/6 (16.7%) | 4/41 (9.8%) | |||||||||||
| Slow speech | 1/16 (6.3%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Hemiparesis | 1/16 (6.3%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Dizziness | 0/16 (0%) | 1/3 (33.3%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Haemorrhage intracranial | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 1/6 (16.7%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Syncope | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Hemiplegia | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 1/6 (16.7%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Seizure | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 1/6 (16.7%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 1/6 (16.7%) | 0/41 (0%) | |||||||||||
| Renal and urinary disorders | ||||||||||||||||||||||
| Micturition frequency | 1/16 (6.3%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Acute kidney injury | 1/16 (6.3%) | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Renal failure | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 1/6 (16.7%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 1/41 (2.4%) | |||||||||||
| Haematuria | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 1/4 (25%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||
| Pulmonary embolism | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 1/4 (25%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Chronic obstructive pulmonary | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Obstructive airways | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 1/9 (11.1%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Pleural effusion | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 1/41 (2.4%) | |||||||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||||
| Rash maculo-papular | 0/16 (0%) | 1/3 (33.3%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Drug eruption | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 1/4 (25%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Vascular disorders | ||||||||||||||||||||||
| Hypotension | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Embolism | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 1/6 (16.7%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||||||||||
| Phase 1b - 28 Day MEK162 45mg+LEE011 200mg | Phase 1b - 28 Day MEK162 45mg+LEE011 250mg | Phase 1b - 28 Day MEK162 30mg+LEE011 300mg | Phase 1b - 28 Day MEK162 45mg+LEE011 300mg | Phase 1b - 21 Day MEK162 30mg+LEE011 200mg | Phase 1b - 21 Day MEK162 45mg+LEE011 200mg | Phase 1b - 21 Day MEK162 30mg+LEE011 300mg | Phase 1b - 21 Day MEK162 45mg+LEE011 300mg | Phase 1b - 21 Day MEK162 45mg+LEE011 450mg | Phase 1b - 21 Day MEK162 45mg+LEE011 600mg | Phase 2 - Dose Expansion Phase | ||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 16/16 (100%) | 3/3 (100%) | 4/4 (100%) | 6/6 (100%) | 5/5 (100%) | 6/6 (100%) | 2/2 (100%) | 4/4 (100%) | 9/9 (100%) | 6/6 (100%) | 41/41 (100%) | |||||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||||||
| Aeaemia | 5/16 (31.3%) | 2/3 (66.7%) | 2/4 (50%) | 4/6 (66.7%) | 2/5 (40%) | 1/6 (16.7%) | 0/2 (0%) | 1/4 (25%) | 4/9 (44.4%) | 0/6 (0%) | 10/41 (24.4%) | |||||||||||
| Neutropenia | 3/16 (18.8%) | 1/3 (33.3%) | 2/4 (50%) | 1/6 (16.7%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 1/4 (25%) | 4/9 (44.4%) | 3/6 (50%) | 5/41 (12.2%) | |||||||||||
| Leukopenia | 4/16 (25%) | 0/3 (0%) | 1/4 (25%) | 1/6 (16.7%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 1/4 (25%) | 1/9 (11.1%) | 2/6 (33.3%) | 1/41 (2.4%) | |||||||||||
| Thrombocytopenia | 2/16 (12.5%) | 1/3 (33.3%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 1/6 (16.7%) | 0/2 (0%) | 1/4 (25%) | 3/9 (33.3%) | 1/6 (16.7%) | 3/41 (7.3%) | |||||||||||
| Lymphopenia | 1/16 (6.3%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 1/6 (16.7%) | 0/2 (0%) | 1/4 (25%) | 2/9 (22.2%) | 2/6 (33.3%) | 1/41 (2.4%) | |||||||||||
| Febrile neutropenia | 0/16 (0%) | 1/3 (33.3%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Granulocytopenia | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 1/4 (25%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Cardiac disorders | ||||||||||||||||||||||
| Angina pectoris | 1/16 (6.3%) | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Cardiac failure | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 0/5 (0%) | 1/6 (16.7%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Cardio-respiratiory arrest | 1/16 (6.3%) | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Eye disorders | ||||||||||||||||||||||
| Chorioretinopathy | 3/16 (18.8%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 1/9 (11.1%) | 2/6 (33.3%) | 0/41 (0%) | |||||||||||
| Retinal detachment | 3/16 (18.8%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 1/5 (20%) | 0/6 (0%) | 0/2 (0%) | 1/4 (25%) | 0/9 (0%) | 2/6 (33.3%) | 6/41 (14.6%) | |||||||||||
| Vision blurred | 2/16 (12.5%) | 0/3 (0%) | 2/4 (50%) | 0/6 (0%) | 0/5 (0%) | 3/6 (50%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 1/6 (16.7%) | 0/41 (0%) | |||||||||||
| Retinopathy | 2/16 (12.5%) | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/5 (20%) | 0/6 (0%) | 0/2 (0%) | 1/4 (25%) | 1/9 (11.1%) | 1/6 (16.7%) | 0/41 (0%) | |||||||||||
| Macular oedema | 1/16 (6.3%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 1/4 (25%) | 2/9 (22.2%) | 1/6 (16.7%) | 5/41 (12.2%) | |||||||||||
| Subretinal fluid | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 1/5 (20%) | 0/6 (0%) | 1/2 (50%) | 1/4 (25%) | 0/9 (0%) | 2/6 (33.3%) | 5/41 (12.2%) | |||||||||||
| Dry eye | 2/16 (12.5%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 1/6 (16.7%) | 0/2 (0%) | 1/4 (25%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Cataract | 1/16 (6.3%) | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 1/4 (25%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Detachment of retinal pigment epithelium | 1/16 (6.3%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 1/2 (50%) | 0/4 (0%) | 1/9 (11.1%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Chorioretinal disorder | 1/16 (6.3%) | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Periorbital oedema | 1/16 (6.3%) | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Retinal disorder | 1/16 (6.3%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 1/9 (11.1%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Gastrointestinal disorders | ||||||||||||||||||||||
| Nausea | 6/16 (37.5%) | 2/3 (66.7%) | 3/4 (75%) | 4/6 (66.7%) | 4/5 (80%) | 3/6 (50%) | 2/2 (100%) | 1/4 (25%) | 1/9 (11.1%) | 1/6 (16.7%) | 22/41 (53.7%) | |||||||||||
| Diarrhoea | 6/16 (37.5%) | 2/3 (66.7%) | 2/4 (50%) | 4/6 (66.7%) | 3/5 (60%) | 4/6 (66.7%) | 2/2 (100%) | 2/4 (50%) | 3/9 (33.3%) | 5/6 (83.3%) | 21/41 (51.2%) | |||||||||||
| Vomiting | 4/16 (25%) | 3/3 (100%) | 4/4 (100%) | 3/6 (50%) | 3/5 (60%) | 2/6 (33.3%) | 1/2 (50%) | 1/4 (25%) | 2/9 (22.2%) | 2/6 (33.3%) | 14/41 (34.1%) | |||||||||||
| Constipation | 3/16 (18.8%) | 1/3 (33.3%) | 2/4 (50%) | 3/6 (50%) | 0/5 (0%) | 1/6 (16.7%) | 0/2 (0%) | 1/4 (25%) | 3/9 (33.3%) | 0/6 (0%) | 8/41 (19.5%) | |||||||||||
| Abdominal pain | 1/16 (6.3%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 1/6 (16.7%) | 2/2 (100%) | 1/4 (25%) | 1/9 (11.1%) | 2/6 (33.3%) | 5/41 (12.2%) | |||||||||||
| Dry mouth | 1/16 (6.3%) | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/5 (20%) | 2/6 (33.3%) | 1/2 (50%) | 1/4 (25%) | 3/9 (33.3%) | 0/6 (0%) | 4/41 (9.8%) | |||||||||||
| Stomatitis | 4/16 (25%) | 0/3 (0%) | 0/4 (0%) | 2/6 (33.3%) | 0/5 (0%) | 1/6 (16.7%) | 0/2 (0%) | 1/4 (25%) | 0/9 (0%) | 0/6 (0%) | 4/41 (9.8%) | |||||||||||
| Gastroesophageal reflux disease | 1/16 (6.3%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 1/5 (20%) | 0/6 (0%) | 0/2 (0%) | 1/4 (25%) | 0/9 (0%) | 0/6 (0%) | 3/41 (7.3%) | |||||||||||
| Dyspepsia | 2/16 (12.5%) | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 2/5 (40%) | 2/6 (33.3%) | 0/2 (0%) | 1/4 (25%) | 1/9 (11.1%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Abdominal distension | 2/16 (12.5%) | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 1/41 (2.4%) | |||||||||||
| Abdominal pain upper | 1/16 (6.3%) | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/5 (20%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Gastritis | 1/16 (6.3%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Gingival pain | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 1/6 (16.7%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Glossodynia | 1/16 (6.3%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| General disorders | ||||||||||||||||||||||
| Oedema peripheral | 7/16 (43.8%) | 2/3 (66.7%) | 2/4 (50%) | 3/6 (50%) | 1/5 (20%) | 2/6 (33.3%) | 0/2 (0%) | 2/4 (50%) | 2/9 (22.2%) | 0/6 (0%) | 18/41 (43.9%) | |||||||||||
| Fatigue | 6/16 (37.5%) | 1/3 (33.3%) | 3/4 (75%) | 0/6 (0%) | 3/5 (60%) | 5/6 (83.3%) | 2/2 (100%) | 1/4 (25%) | 3/9 (33.3%) | 2/6 (33.3%) | 15/41 (36.6%) | |||||||||||
| Pyrexia | 2/16 (12.5%) | 2/3 (66.7%) | 1/4 (25%) | 0/6 (0%) | 2/5 (40%) | 1/6 (16.7%) | 0/2 (0%) | 2/4 (50%) | 2/9 (22.2%) | 2/6 (33.3%) | 11/41 (26.8%) | |||||||||||
| Chills | 0/16 (0%) | 1/3 (33.3%) | 1/4 (25%) | 0/6 (0%) | 2/5 (40%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 1/9 (11.1%) | 1/6 (16.7%) | 6/41 (14.6%) | |||||||||||
| Face oedema | 3/16 (18.8%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 1/4 (25%) | 1/9 (11.1%) | 0/6 (0%) | 1/41 (2.4%) | |||||||||||
| Pain | 1/16 (6.3%) | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 1/9 (11.1%) | 0/6 (0%) | 0/41 (0%) | |||||||||||
| Astenia | 0/16 (0%) | 0/3 (0%) | 0/4 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/2 (0%) | 0/4 (0%) | 0/9 (0%) | 1/6 (16.7%) | 3/41 (7.3%) | |||||||||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The terms and conditions of the sponsor's agreements with its investigators may vary. However, the sponsor does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e., data from all sites) in the clinical trials.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Pfizer |
| Phone | 1-800-718-1021 |
| ClinicalTrials.gov_Inquiries@pfizer.com |
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT01781572
Other Study ID Numbers:
- CMEK162X2114
- C4211005
First Posted:
Feb 1, 2013
Last Update Posted:
Dec 7, 2020
Last Verified:
Nov 1, 2020