Safety and Efficacy of LEE011 and LGX818 in Patients With BRAF Mutant Melanoma.
Sponsor
Array BioPharma (Industry)
Overall Status
Terminated
CT.gov ID
NCT01777776
Collaborator
(none)
28
9
4
21
3.1
0.1
Study Details
Study Description
Brief Summary
To evaluate the safety, tolerability and efficacy of LEE011 and LGX818 when administered orally to patients with BRAF mutant melanoma.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Detailed Description
In response to developments in the treatment of melanoma, the sponsor reviewed the data from the ongoing study and decided to halt further enrollment of patients in the Phase Ib part of the study. Consequently, the Phase II part of the study was not performed. Early termination of the study was not due to any safety concerns.
Study Design
Study Type:
Interventional
Actual Enrollment
:
28 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase Ib/II, Multicenter, Study of LEE011 in Combination With LGX818 in Adult Patients With BRAF Mutant Melanoma.
Study Start Date
:
Jul 1, 2013
Actual Primary Completion Date
:
Apr 1, 2015
Actual Study Completion Date
:
Apr 1, 2015
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Phase Ib Phase Ib will randomize 18 patients with BRAF mutant melanoma, who are naïve or who have progressed on prior therapy to evaluate the safety and tolerability of the combination of LEE011 and LGX818. |
Drug: LEE011
LEE011 will be administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle).
Other Names:
Drug: LGX818
LGX818 will be administered orally, once daily on a continuous dosing schedule (28-day cycle).
Other Names:
|
| Experimental: Phase II arm 1a Phase II arm 1a will randomize 60 patients that are naïve to prior BRAF inhibitor therapy to LGX818+LEE011 to evaluate the effect of adding LEE011 to a BRAFi in this population. |
Drug: LEE011
LEE011 will be administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle).
Other Names:
Drug: LGX818
LGX818 will be administered orally, once daily on a continuous dosing schedule (28-day cycle).
Other Names:
|
| Experimental: Phase II arm 1b Phase II arm 1b will randomize 30 patients to LGX818. Single agent anti-tumor activity of LGX818 is comparable to other BRAFi that are either approved or in clinical trials. This single agent anti-tumor activity will be compared to that of the combination (LEE011 + LGX818) in the BRAFi naïve patient population. |
Drug: LGX818
LGX818 will be administered orally, once daily on a continuous dosing schedule (28-day cycle).
Other Names:
|
| Experimental: Phase II arm 2 Phase II arm 2 will evaluate a single arm LEE011+LGX818 in 40 patients resistant to prior BRAF inhibitor therapy. Single agent LGX818 has shown limited activity in patients with melanoma who have failed prior BRAF inhibitor treatment; the contribution of LEE011 in this combination will be evaluated. |
Drug: LEE011
LEE011 will be administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle).
Other Names:
Drug: LGX818
LGX818 will be administered orally, once daily on a continuous dosing schedule (28-day cycle).
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Phase Ib - Incidence of Dose Limiting Toxicities (DLTs) in Cycle 1 [Cycle 1 (approximately 28 days)]
Dose Limiting Toxicities (DLTs) during the first 28 days of the combination treatment of LEE011 and LGX818. Due to the halt of enrollment, no Maximum Tolerated Dose (MTD) was formally declared during the study.
- Phase II - Progression Free Survival (PFS) [Approximately 23 months after enrollment]
As per RECIST v1.1, PFS is the time from date of randomization/ start of treatment to the date of event defined as the first documented progression or death due to any cause. Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to efficacy were not performed.
- Phase II - Objective Response Rate (ORR) [Approximately 23 months after enrollment]
As per RECIST v1.1, ORR is defined as the proportion of patients with a best overall response of complete response or partial response. Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to efficacy were not performed.
Secondary Outcome Measures
- Phase I - Number of Subjects Experiencing at Least One Adverse Event (AE). [Approximately 23 months after enrollment]
- Phase I - Number of Subjects Experiencing at Least One Serious Adverse Event (SAE). [Approximately 23 months after enrollment]
- Phase Ib/II - Plasma Concentration-time Profiles [28-day cycles]
Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to plasma concentration time profiles were not performed.
- Phase Ib/II - Overall Response Rate (ORR) [Approximately 23 months after enrollment]
ORR is defined as the proportion of patients with a best overall response of complete response or partial response. Due to the halt of enrollment during the Phase Ib part of the study, this analysis was not performed.
- Phase Ib/II - Progression Free Survival (PFS) [Approximately 23 months after enrollment]
PFS is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. Due to the halt of enrollment during the Phase Ib part of the study, this analysis was not performed.
- Phase Ib/II - Duration Of Response (DOR) [Approximately 23 months after enrollment]
DOR is calculated as the time from the date of first documented response (complete response (CR) or partial response (PR)) to the first documented date of progression or death due to underlying cancer. Due to the halt of enrollment during the Phase Ib part of the study, this analysis was not performed.
- Phase II - Overall Survival (OS) [Approximately 23 months after enrollment]
OS is defined as the time from date of randomization/start of treatment to date of death due to any cause. If a patient is not known to have died, survival will be censored at the date of last known date patient alive. Due to the halt of enrollment during the Phase Ib part of the study, this analysis was not performed.
- Phase Ib/II - Pharmacokinetic Parameters: AUCtau [28-day cycles]
Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to pharmacokinetic parameters were not performed.
- Phase Ib/II - Pharmacokinetic Parameters: Cmin [28-day cycles]
Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to pharmacokinetic parameters were not performed.
- Phase Ib/II - Pharmacokinetic Parameters: Cmax [28-day cycles]
Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to pharmacokinetic parameters were not performed.
- Phase Ib/II - Pharmacokinetic Parameters: Tmax [28-day cycles]
Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to pharmacokinetic parameters were not performed.
- Phase Ib/II - Pharmacokinetic Parameters: Racc [28-day cycles]
Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to pharmacokinetic parameters were not performed.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Age ≥18 years.
-
Diagnosis of locally advanced or metastatic melanoma along with written documentation of BRAF V600 mutation.
-
ECOG performance status of 0 - 2.
-
Patients enrolled into Phase Ib must have evidence of evaluable and/or measurable disease as determined by RECIST v1.1.
-
Patients enrolled into Phase II (BRAFi naïve and resistant) must have evidence of measurable disease as determined by RECIST v1.1.
-
Archival tumor tissue must be obtained for patients enrolled in Phase Ib and Phase II arm 1a/b- BRAFi naïve patients. If an archival tumor tissue is not available, a fresh tumor sample is acceptable.
-
For patients enrolled in the phase II arm 2, patients must agree to undergo a fresh tumor biopsy unless one was collected prior to study entry but at the time of disease relapse from the most recent BRAFi treatment.
Exclusion Criteria:
-
Symptomatic brain metastases.
-
Symptomatic or untreated leptomeningeal disease.
-
Patients with inadequate laboratory values during screening.
-
In the phase II BRAFi naïve arms (1a/b), prior exposure to CDK4/6 inhibitor (e.g., PD
-
Impaired cardiac function or clinically significant cardiac diseases.
-
Impairment of gastro-intestinal (GI) function or GI disease that may significantly alter the absorption of LEE011 or LGX818.
-
Patients with concurrent severe and/or uncontrolled concurrent medical conditions.
-
Previous or concurrent malignancy.
-
Major surgery < 2 weeks before starting study treatment
-
Known diagnosis of human immunodeficiency virus (HIV) or hepatitis C.
Other protocol-defined inclusion/exclusion criteria may apply.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Colorado Dept of Oncology | Aurora | Colorado | United States | 80045 |
| 2 | Karmanos Cancer Institute Dept of Oncology | Detroit | Michigan | United States | 48201 |
| 3 | Memorial Sloan Kettering Cancer Center Dept Oncology | NY | New York | United States | 90033 |
| 4 | Oregon Health & Science University Dept. of OHSU (3) | Portland | Oregon | United States | 97239 |
| 5 | Vanderbilt University Medical Center SC - Dept of Oncology . | Nashville | Tennessee | United States | 37232 |
| 6 | Novartis Investigative Site | Westmead | New South Wales | Australia | 2145 |
| 7 | Novartis Investigative Site | Woodville | South Australia | Australia | 5011 |
| 8 | Novartis Investigative Site | Montreal | Quebec | Canada | H2X 3J4 |
| 9 | Novartis Investigative Site | Utrecht | Netherlands | 3584CX |
Sponsors and Collaborators
- Array BioPharma
Investigators
- Study Director: Array BioPharma, 303-381-6604
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Array BioPharma
ClinicalTrials.gov Identifier:
NCT01777776
Other Study ID Numbers:
- CLEE011X2105
First Posted:
Jan 29, 2013
Last Update Posted:
Sep 13, 2016
Last Verified:
Jul 1, 2016
Keywords provided by Array BioPharma
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Recruitment to CLEE011X2105 began on 10-July-2013. The study concluded on 13-April-2015. Participant Flow data is comprised of the Full Analysis Set (FAS), which is all patients who received at least one dose of LGX818 or LEE011. Not completed subjects represents subjects that stopped treatment early, due to the corresponding reason. |
|---|---|
| Pre-assignment Detail | In response to developments in the treatment of melanoma, the sponsor reviewed the data from the ongoing study and decided to halt further enrollment of patients in the Phase Ib part of the study. Consequently, the Phase II part of the study was not performed. Early termination of the study was not due to any safety concerns. |
| Arm/Group Title | Phase Ib: LEE011 200 mg + LGX818 300 mg (Cohort) | Phase Ib: LEE011 300 mg + LGX818 200 mg (Cohort) | Phase Ib: LEE011 400 mg + LGX818 100 mg (Cohort) | Phase Ib: LEE011 400 mg + LGX818 200 mg (Cohort) |
|---|---|---|---|---|
| Arm/Group Description | Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment. | Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment. | Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment. | Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment. |
| Period Title: Overall Study | ||||
| STARTED | 6 | 12 | 6 | 4 |
| COMPLETED | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 6 | 12 | 6 | 4 |
Baseline Characteristics
| Arm/Group Title | Phase Ib: LEE011 200 mg + LGX818 300 mg (Cohort) | Phase Ib: LEE011 300 mg + LGX818 200 mg (Cohort) | Phase Ib: LEE011 400 mg + LGX818 100 mg (Cohort) | Phase Ib: LEE011 400 mg + LGX818 200 mg (Cohort) | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment. | Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment. | Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment. | Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment. | Total of all reporting groups |
| Overall Participants | 6 | 12 | 6 | 4 | 28 |
| Age (Count of Participants) | |||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
2
33.3%
|
10
83.3%
|
4
66.7%
|
2
50%
|
18
64.3%
|
| >=65 years |
4
66.7%
|
2
16.7%
|
2
33.3%
|
2
50%
|
10
35.7%
|
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
65.0
(10.71)
|
49.8
(13.66)
|
58.0
(10.55)
|
62.0
(17.63)
|
56.6
(13.90)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
3
50%
|
7
58.3%
|
1
16.7%
|
0
0%
|
11
39.3%
|
| Male |
3
50%
|
5
41.7%
|
5
83.3%
|
4
100%
|
17
60.7%
|
| Weight (kilograms) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [kilograms] |
84.60
(12.793)
|
78.08
(17.069)
|
80.17
(10.308)
|
74.70
(16.415)
|
79.44
(14.450)
|
| WHO/ECOG performance status (participants) [Number] | |||||
| 0 |
2
33.3%
|
4
33.3%
|
1
16.7%
|
1
25%
|
8
28.6%
|
| 1 |
4
66.7%
|
7
58.3%
|
5
83.3%
|
3
75%
|
19
67.9%
|
| 2 |
0
0%
|
1
8.3%
|
0
0%
|
0
0%
|
1
3.6%
|
Outcome Measures
| Title | Phase Ib - Incidence of Dose Limiting Toxicities (DLTs) in Cycle 1 |
|---|---|
| Description | Dose Limiting Toxicities (DLTs) during the first 28 days of the combination treatment of LEE011 and LGX818. Due to the halt of enrollment, no Maximum Tolerated Dose (MTD) was formally declared during the study. |
| Time Frame | Cycle 1 (approximately 28 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis group is comprised of the Safety Set (SS), which includes all patients who received at least one dose of LEE011 or LGX818, and have at least one valid post-baseline safety assessment. |
| Arm/Group Title | Phase Ib: LEE011 200 mg + LGX818 300 mg (Cohort) | Phase Ib: LEE011 300 mg + LGX818 200 mg (Cohort) | Phase Ib: LEE011 400 mg + LGX818 100 mg (Cohort) | Phase Ib: LEE011 400 mg + LGX818 200 mg (Cohort) |
|---|---|---|---|---|
| Arm/Group Description | Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment. | Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment. | Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment. | Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment. |
| Measure Participants | 6 | 12 | 6 | 4 |
| Myalagia |
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
| Elevated Bilirubin |
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
| Neuralgia |
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
| Maculopapular Rash |
0
0%
|
0
0%
|
0
0%
|
1
25%
|
| Title | Phase II - Progression Free Survival (PFS) |
|---|---|
| Description | As per RECIST v1.1, PFS is the time from date of randomization/ start of treatment to the date of event defined as the first documented progression or death due to any cause. Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to efficacy were not performed. |
| Time Frame | Approximately 23 months after enrollment |
Outcome Measure Data
| Analysis Population Description |
|---|
| This analysis set would have been the Full Analysis (FAS), which included all patients who received at least one dose of encorafenib or ribociclib. |
| Arm/Group Title | Phase II - Arm 1a (LGX818+LEE011) | Phase II - Arm 1b (LGX818) |
|---|---|---|
| Arm/Group Description | Patients naïve to prior BRAF inhibitor therapy were administered LGX818+LEE011 to evaluate the effect of adding LEE011 to a BRAFi in this population. LEE011: Administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle). LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle). | Patients administered LGX818. Single agent anti-tumor activity of LGX818 is comparable to other BRAFi that are either approved or in clinical trials. This single agent anti-tumor activity will be compared to that of the combination (LEE011 + LGX818) in the BRAFi naïve patient population. LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle). |
| Measure Participants | 0 | 0 |
| Title | Phase II - Objective Response Rate (ORR) |
|---|---|
| Description | As per RECIST v1.1, ORR is defined as the proportion of patients with a best overall response of complete response or partial response. Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to efficacy were not performed. |
| Time Frame | Approximately 23 months after enrollment |
Outcome Measure Data
| Analysis Population Description |
|---|
| This analysis set would have been the Full Analysis (FAS), which included all patients who received at least one dose of encorafenib or ribociclib. |
| Arm/Group Title | Phase II - Arm 2 (BRAFi Resistant) |
|---|---|
| Arm/Group Description | Patients with BRAF V600 mutant melanoma who are resistant to selective BRAFi treatment will be enrolled into LEE011+ LGX818. |
| Measure Participants | 0 |
| Title | Phase I - Number of Subjects Experiencing at Least One Adverse Event (AE). |
|---|---|
| Description | |
| Time Frame | Approximately 23 months after enrollment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis group is comprised of the Safety Set (SS), which includes all patients who received at least one dose of LEE011 or LGX818, and have at least one valid post-baseline safety assessment. |
| Arm/Group Title | Phase Ib: LEE011 200 mg + LGX818 300 mg (Cohort) | Phase Ib: LEE011 300 mg + LGX818 200 mg (Cohort) | Phase Ib: LEE011 400 mg + LGX818 100 mg (Cohort) | Phase Ib: LEE011 400 mg + LGX818 200 mg (Cohort) |
|---|---|---|---|---|
| Arm/Group Description | Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment. | Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment. | Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment. | Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment. |
| Measure Participants | 6 | 12 | 6 | 4 |
| Number [participants] |
6
100%
|
12
100%
|
6
100%
|
4
100%
|
| Title | Phase I - Number of Subjects Experiencing at Least One Serious Adverse Event (SAE). |
|---|---|
| Description | |
| Time Frame | Approximately 23 months after enrollment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis group is comprised of the Safety Set (SS), which is all patients who received at least one dose of LEE011 or LGX818, and have at least one valid post-baseline safety assessment. |
| Arm/Group Title | Phase Ib: LEE011 200 mg + LGX818 300 mg (Cohort) | Phase Ib: LEE011 300 mg + LGX818 200 mg (Cohort) | Phase Ib: LEE011 400 mg + LGX818 100 mg (Cohort) | Phase Ib: LEE011 400 mg + LGX818 200 mg (Cohort) |
|---|---|---|---|---|
| Arm/Group Description | Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment. | Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment. | Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment. | Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment. |
| Measure Participants | 6 | 12 | 6 | 4 |
| Number [participants] |
3
50%
|
5
41.7%
|
3
50%
|
1
25%
|
| Title | Phase Ib/II - Plasma Concentration-time Profiles |
|---|---|
| Description | Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to plasma concentration time profiles were not performed. |
| Time Frame | 28-day cycles |
Outcome Measure Data
| Analysis Population Description |
|---|
| This analysis group would have been the PK analysis set (PAS), which would have consisted of all patients who had at least one blood sample providing evaluable drug concentration data. |
| Arm/Group Title | Phase I (Dose Escalation) | Phase II - Arm 1a (LGX818+LEE011) | Phase II - Arm 1b (LGX818) | Phase II - Arm 2 (BRAFi Resistant) |
|---|---|---|---|---|
| Arm/Group Description | Adult patients with locally advanced or metastatic BRAF V600 mutant melanoma who are resistant to selective BRAFi treatment or patients who are naïve to selective BRAFi treatment. LEE011: Administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle). LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle). | Patients naïve to prior BRAF inhibitor therapy were administered LGX818+LEE011 to evaluate the effect of adding LEE011 to a BRAFi in this population. LEE011: Administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle). LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle). | Patients administered LGX818. Single agent anti-tumor activity of LGX818 is comparable to other BRAFi that are either approved or in clinical trials. This single agent anti-tumor activity will be compared to that of the combination (LEE011 + LGX818) in the BRAFi naïve patient population. LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle). | Patients with BRAF V600 mutant melanoma who are resistant to selective BRAFi treatment will be enrolled into LEE011+ LGX818. |
| Measure Participants | 0 | 0 | 0 | 0 |
| Title | Phase Ib/II - Overall Response Rate (ORR) |
|---|---|
| Description | ORR is defined as the proportion of patients with a best overall response of complete response or partial response. Due to the halt of enrollment during the Phase Ib part of the study, this analysis was not performed. |
| Time Frame | Approximately 23 months after enrollment |
Outcome Measure Data
| Analysis Population Description |
|---|
| This analysis set would have been the Full Analysis (FAS), which included all patients who received at least one dose of encorafenib or ribociclib. |
| Arm/Group Title | Phase I (Dose Escalation) | Phase II - Arm 1a (LGX818+LEE011) | Phase II - Arm 1b (LGX818) |
|---|---|---|---|
| Arm/Group Description | Adult patients with locally advanced or metastatic BRAF V600 mutant melanoma who are resistant to selective BRAFi treatment or patients who are naïve to selective BRAFi treatment. LEE011: Administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle). LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle). | Patients naïve to prior BRAF inhibitor therapy were administered LGX818+LEE011 to evaluate the effect of adding LEE011 to a BRAFi in this population. LEE011: Administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle). LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle). | Patients administered LGX818. Single agent anti-tumor activity of LGX818 is comparable to other BRAFi that are either approved or in clinical trials. This single agent anti-tumor activity will be compared to that of the combination (LEE011 + LGX818) in the BRAFi naïve patient population. LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle). |
| Measure Participants | 0 | 0 | 0 |
| Title | Phase Ib/II - Progression Free Survival (PFS) |
|---|---|
| Description | PFS is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. Due to the halt of enrollment during the Phase Ib part of the study, this analysis was not performed. |
| Time Frame | Approximately 23 months after enrollment |
Outcome Measure Data
| Analysis Population Description |
|---|
| This analysis set would have been the Full Analysis (FAS), which included all patients who received at least one dose of encorafenib or ribociclib. |
| Arm/Group Title | Phase I (Dose Escalation) | Phase II - Arm 2 (BRAFi Resistant) |
|---|---|---|
| Arm/Group Description | Adult patients with locally advanced or metastatic BRAF V600 mutant melanoma who are resistant to selective BRAFi treatment or patients who are naïve to selective BRAFi treatment. LEE011: Administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle). LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle). | Patients with BRAF V600 mutant melanoma who are resistant to selective BRAFi treatment will be enrolled into LEE011+ LGX818. |
| Measure Participants | 0 | 0 |
| Title | Phase Ib/II - Duration Of Response (DOR) |
|---|---|
| Description | DOR is calculated as the time from the date of first documented response (complete response (CR) or partial response (PR)) to the first documented date of progression or death due to underlying cancer. Due to the halt of enrollment during the Phase Ib part of the study, this analysis was not performed. |
| Time Frame | Approximately 23 months after enrollment |
Outcome Measure Data
| Analysis Population Description |
|---|
| This analysis set would have been the Full Analysis (FAS), which included all patients who received at least one dose of encorafenib or ribociclib. |
| Arm/Group Title | Phase I (Dose Escalation) | Phase II - Arm 1a (LGX818+LEE011) | Phase II - Arm 1b (LGX818) | Phase II - Arm 2 (BRAFi Resistant) |
|---|---|---|---|---|
| Arm/Group Description | Adult patients with locally advanced or metastatic BRAF V600 mutant melanoma who are resistant to selective BRAFi treatment or patients who are naïve to selective BRAFi treatment. LEE011: Administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle). LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle). | Patients naïve to prior BRAF inhibitor therapy were administered LGX818+LEE011 to evaluate the effect of adding LEE011 to a BRAFi in this population. LEE011: Administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle). LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle). | Patients administered LGX818. Single agent anti-tumor activity of LGX818 is comparable to other BRAFi that are either approved or in clinical trials. This single agent anti-tumor activity will be compared to that of the combination (LEE011 + LGX818) in the BRAFi naïve patient population. LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle). | Patients with BRAF V600 mutant melanoma who are resistant to selective BRAFi treatment will be enrolled into LEE011+ LGX818. |
| Measure Participants | 0 | 0 | 0 | 0 |
| Title | Phase II - Overall Survival (OS) |
|---|---|
| Description | OS is defined as the time from date of randomization/start of treatment to date of death due to any cause. If a patient is not known to have died, survival will be censored at the date of last known date patient alive. Due to the halt of enrollment during the Phase Ib part of the study, this analysis was not performed. |
| Time Frame | Approximately 23 months after enrollment |
Outcome Measure Data
| Analysis Population Description |
|---|
| This analysis set would have been the Full Analysis (FAS), which included all patients who received at least one dose of encorafenib or ribociclib. |
| Arm/Group Title | Phase II - Arm 1a (LGX818+LEE011) | Phase II - Arm 1b (LGX818) | Phase II - Arm 2 (BRAFi Resistant) |
|---|---|---|---|
| Arm/Group Description | Patients naïve to prior BRAF inhibitor therapy were administered LGX818+LEE011 to evaluate the effect of adding LEE011 to a BRAFi in this population. LEE011: Administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle). LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle). | Patients administered LGX818. Single agent anti-tumor activity of LGX818 is comparable to other BRAFi that are either approved or in clinical trials. This single agent anti-tumor activity will be compared to that of the combination (LEE011 + LGX818) in the BRAFi naïve patient population. LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle). | Patients with BRAF V600 mutant melanoma who are resistant to selective BRAFi treatment will be enrolled into LEE011+ LGX818. |
| Measure Participants | 0 | 0 | 0 |
| Title | Phase Ib/II - Pharmacokinetic Parameters: AUCtau |
|---|---|
| Description | Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to pharmacokinetic parameters were not performed. |
| Time Frame | 28-day cycles |
Outcome Measure Data
| Analysis Population Description |
|---|
| This analysis group would have been the PK analysis set (PAS), which would have consisted of all patients who had at least one blood sample providing evaluable drug concentration data. |
| Arm/Group Title | Phase I (Dose Escalation) | Phase II - Arm 1a (LGX818+LEE011) | Phase II - Arm 1b (LGX818) | Phase II - Arm 2 (BRAFi Resistant) |
|---|---|---|---|---|
| Arm/Group Description | Adult patients with locally advanced or metastatic BRAF V600 mutant melanoma who are resistant to selective BRAFi treatment or patients who are naïve to selective BRAFi treatment. LEE011: Administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle). LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle). | Patients naïve to prior BRAF inhibitor therapy were administered LGX818+LEE011 to evaluate the effect of adding LEE011 to a BRAFi in this population. LEE011: Administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle). LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle). | Patients administered LGX818. Single agent anti-tumor activity of LGX818 is comparable to other BRAFi that are either approved or in clinical trials. This single agent anti-tumor activity will be compared to that of the combination (LEE011 + LGX818) in the BRAFi naïve patient population. LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle). | Patients with BRAF V600 mutant melanoma who are resistant to selective BRAFi treatment will be enrolled into LEE011+ LGX818. |
| Measure Participants | 0 | 0 | 0 | 0 |
| Title | Phase Ib/II - Pharmacokinetic Parameters: Cmin |
|---|---|
| Description | Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to pharmacokinetic parameters were not performed. |
| Time Frame | 28-day cycles |
Outcome Measure Data
| Analysis Population Description |
|---|
| This analysis group would have been the PK analysis set (PAS), which would have consisted of all patients who had at least one blood sample providing evaluable drug concentration data. |
| Arm/Group Title | Phase I (Dose Escalation) | Phase II - Arm 1a (LGX818+LEE011) | Phase II - Arm 1b (LGX818) | Phase II - Arm 2 (BRAFi Resistant) |
|---|---|---|---|---|
| Arm/Group Description | Adult patients with locally advanced or metastatic BRAF V600 mutant melanoma who are resistant to selective BRAFi treatment or patients who are naïve to selective BRAFi treatment. LEE011: Administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle). LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle). | Patients naïve to prior BRAF inhibitor therapy were administered LGX818+LEE011 to evaluate the effect of adding LEE011 to a BRAFi in this population. LEE011: Administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle). LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle). | Patients administered LGX818. Single agent anti-tumor activity of LGX818 is comparable to other BRAFi that are either approved or in clinical trials. This single agent anti-tumor activity will be compared to that of the combination (LEE011 + LGX818) in the BRAFi naïve patient population. LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle). | Patients with BRAF V600 mutant melanoma who are resistant to selective BRAFi treatment will be enrolled into LEE011+ LGX818. |
| Measure Participants | 0 | 0 | 0 | 0 |
| Title | Phase Ib/II - Pharmacokinetic Parameters: Cmax |
|---|---|
| Description | Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to pharmacokinetic parameters were not performed. |
| Time Frame | 28-day cycles |
Outcome Measure Data
| Analysis Population Description |
|---|
| This analysis group would have been the PK analysis set (PAS), which would have consisted of all patients who had at least one blood sample providing evaluable drug concentration data. |
| Arm/Group Title | Phase I (Dose Escalation) | Phase II - Arm 1a (LGX818+LEE011) | Phase II - Arm 1b (LGX818) | Phase II - Arm 2 (BRAFi Resistant) |
|---|---|---|---|---|
| Arm/Group Description | Adult patients with locally advanced or metastatic BRAF V600 mutant melanoma who are resistant to selective BRAFi treatment or patients who are naïve to selective BRAFi treatment. LEE011: Administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle). LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle). | Patients naïve to prior BRAF inhibitor therapy were administered LGX818+LEE011 to evaluate the effect of adding LEE011 to a BRAFi in this population. LEE011: Administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle). LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle). | Patients administered LGX818. Single agent anti-tumor activity of LGX818 is comparable to other BRAFi that are either approved or in clinical trials. This single agent anti-tumor activity will be compared to that of the combination (LEE011 + LGX818) in the BRAFi naïve patient population. LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle). | Patients with BRAF V600 mutant melanoma who are resistant to selective BRAFi treatment will be enrolled into LEE011+ LGX818. |
| Measure Participants | 0 | 0 | 0 | 0 |
| Title | Phase Ib/II - Pharmacokinetic Parameters: Tmax |
|---|---|
| Description | Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to pharmacokinetic parameters were not performed. |
| Time Frame | 28-day cycles |
Outcome Measure Data
| Analysis Population Description |
|---|
| This analysis group would have been the PK analysis set (PAS), which would have consisted of all patients who had at least one blood sample providing evaluable drug concentration data. |
| Arm/Group Title | Phase I (Dose Escalation) | Phase II - Arm 1a (LGX818+LEE011) | Phase II - Arm 1b (LGX818) | Phase II - Arm 2 (BRAFi Resistant) |
|---|---|---|---|---|
| Arm/Group Description | Adult patients with locally advanced or metastatic BRAF V600 mutant melanoma who are resistant to selective BRAFi treatment or patients who are naïve to selective BRAFi treatment. LEE011: Administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle). LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle). | Patients naïve to prior BRAF inhibitor therapy were administered LGX818+LEE011 to evaluate the effect of adding LEE011 to a BRAFi in this population. LEE011: Administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle). LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle). | Patients administered LGX818. Single agent anti-tumor activity of LGX818 is comparable to other BRAFi that are either approved or in clinical trials. This single agent anti-tumor activity will be compared to that of the combination (LEE011 + LGX818) in the BRAFi naïve patient population. LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle). | Patients with BRAF V600 mutant melanoma who are resistant to selective BRAFi treatment will be enrolled into LEE011+ LGX818. |
| Measure Participants | 0 | 0 | 0 | 0 |
| Title | Phase Ib/II - Pharmacokinetic Parameters: Racc |
|---|---|
| Description | Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to pharmacokinetic parameters were not performed. |
| Time Frame | 28-day cycles |
Outcome Measure Data
| Analysis Population Description |
|---|
| This analysis group would have been the PK analysis set (PAS), which would have consisted of all patients who had at least one blood sample providing evaluable drug concentration data. |
| Arm/Group Title | Phase I (Dose Escalation) | Phase II - Arm 1a (LGX818+LEE011) | Phase II - Arm 1b (LGX818) | Phase II - Arm 2 (BRAFi Resistant) |
|---|---|---|---|---|
| Arm/Group Description | Adult patients with locally advanced or metastatic BRAF V600 mutant melanoma who are resistant to selective BRAFi treatment or patients who are naïve to selective BRAFi treatment. LEE011: Administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle). LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle). | Patients naïve to prior BRAF inhibitor therapy were administered LGX818+LEE011 to evaluate the effect of adding LEE011 to a BRAFi in this population. LEE011: Administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle). LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle). | Patients administered LGX818. Single agent anti-tumor activity of LGX818 is comparable to other BRAFi that are either approved or in clinical trials. This single agent anti-tumor activity will be compared to that of the combination (LEE011 + LGX818) in the BRAFi naïve patient population. LGX818: Administered orally, once daily on a continuous dosing schedule (28-day cycle). | Patients with BRAF V600 mutant melanoma who are resistant to selective BRAFi treatment will be enrolled into LEE011+ LGX818. |
| Measure Participants | 0 | 0 | 0 | 0 |
Adverse Events
| Time Frame | This study began recruitment on 10-July-2013 and concluded on 13-April-2015. Adverse Events (AEs) were collected throughout the study, approximately 2 years. | |||||||
|---|---|---|---|---|---|---|---|---|
| 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 Ib: LEE011 200 mg + LGX818 300 mg (Cohort) | Phase Ib: LEE011 300 mg + LGX818 200 mg (Cohort) | Phase Ib: LEE011 400 mg + LGX818 100 mg (Cohort) | Phase Ib: LEE011 400 mg + LGX818 200 mg (Cohort) | ||||
| Arm/Group Description | Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment. | Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment. | Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment. | Ribociclib (LEE011) was provided in capsule form for oral use and was to be taken orally, once a day for 21 consecutive days followed by a 7-day planned break as part of each 28-day cycle of treatment. Encorafenib (LGX818) was to be provided in capsule form for oral use and taken orally, once a day for 28 consecutive days as part of each 28-day cycle of treatment. | ||||
All Cause Mortality |
||||||||
| Phase Ib: LEE011 200 mg + LGX818 300 mg (Cohort) | Phase Ib: LEE011 300 mg + LGX818 200 mg (Cohort) | Phase Ib: LEE011 400 mg + LGX818 100 mg (Cohort) | Phase Ib: LEE011 400 mg + LGX818 200 mg (Cohort) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| Phase Ib: LEE011 200 mg + LGX818 300 mg (Cohort) | Phase Ib: LEE011 300 mg + LGX818 200 mg (Cohort) | Phase Ib: LEE011 400 mg + LGX818 100 mg (Cohort) | Phase Ib: LEE011 400 mg + LGX818 200 mg (Cohort) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/6 (50%) | 5/12 (41.7%) | 3/6 (50%) | 1/4 (25%) | ||||
| Gastrointestinal disorders | ||||||||
| Nausea | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Hepatobiliary disorders | ||||||||
| Transaminases increased | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Immune system disorders | ||||||||
| Systemic inflammatory response syndrome | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Infections and infestations | ||||||||
| Pneumonia | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Sepsis | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||
| Brain oedema | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 1/4 (25%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Chest wall abscess | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Failure to thrive | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Neck pain | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Nervous system disorders | ||||||||
| Memory impairment | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Seizure | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Simple partial seizures | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Spinal cord compression | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Psychiatric disorders | ||||||||
| Confusional state | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Mental status changes | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Renal and urinary disorders | ||||||||
| Urinary tract infection | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||
| Dermatitis bullous | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Vascular disorders | ||||||||
| Syncope | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||
| Phase Ib: LEE011 200 mg + LGX818 300 mg (Cohort) | Phase Ib: LEE011 300 mg + LGX818 200 mg (Cohort) | Phase Ib: LEE011 400 mg + LGX818 100 mg (Cohort) | Phase Ib: LEE011 400 mg + LGX818 200 mg (Cohort) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/6 (100%) | 12/12 (100%) | 6/6 (100%) | 4/4 (100%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 1/6 (16.7%) | 1 | 1/12 (8.3%) | 1 | 2/6 (33.3%) | 2 | 1/4 (25%) | 1 |
| Lymphopenia | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 2/4 (50%) | 2 |
| Neutropenia | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Thrombocytopenia | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Disseminated intravascular coagulation | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Increased tendency to bruise | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Leukopenia | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Lymphadenopathy | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Cardiac disorders | ||||||||
| Tachycardia | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 2/4 (50%) | 2 |
| Palpitations | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Ear and labyrinth disorders | ||||||||
| Ear pruritus | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Endocrine disorders | ||||||||
| Adrenal insufficiency | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Cushingoid | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Eye disorders | ||||||||
| Eye pruritus | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Vision blurred | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Blepharospasm | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Dry eye | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Eye discharge | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Photophobia | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Gastrointestinal disorders | ||||||||
| Nausea | 2/6 (33.3%) | 2 | 6/12 (50%) | 6 | 4/6 (66.7%) | 4 | 4/4 (100%) | 4 |
| Vomiting | 1/6 (16.7%) | 1 | 3/12 (25%) | 3 | 3/6 (50%) | 3 | 2/4 (50%) | 2 |
| Constipation | 3/6 (50%) | 3 | 3/12 (25%) | 3 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Diarrhoea | 2/6 (33.3%) | 2 | 2/12 (16.7%) | 2 | 1/6 (16.7%) | 1 | 2/4 (50%) | 2 |
| Stomatitis | 1/6 (16.7%) | 1 | 4/12 (33.3%) | 4 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Abdominal distension | 0/6 (0%) | 0 | 2/12 (16.7%) | 2 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Abdominal pain | 0/6 (0%) | 0 | 2/12 (16.7%) | 2 | 0/6 (0%) | 0 | 1/4 (25%) | 1 |
| Dyspepsia | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Oral pain | 0/6 (0%) | 0 | 2/12 (16.7%) | 2 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Abdominal discomfort | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Abdominal pain upper | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Cheilitis | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Dysphagia | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Gingival discolouration | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Gingival ulceration | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Glossitis | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Glossodynia | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Haemorrhoidal haemorrhage | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Haemorrhoids | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Retching | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| General disorders | ||||||||
| Fatigue | 2/6 (33.3%) | 2 | 6/12 (50%) | 6 | 4/6 (66.7%) | 4 | 3/4 (75%) | 3 |
| Oedema peripheral | 0/6 (0%) | 0 | 2/12 (16.7%) | 2 | 2/6 (33.3%) | 2 | 0/4 (0%) | 0 |
| Chills | 1/6 (16.7%) | 1 | 2/12 (16.7%) | 2 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Pyrexia | 0/6 (0%) | 0 | 2/12 (16.7%) | 2 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Localised oedema | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Non-cardiac chest pain | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Peripheral swelling | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Xerosis | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Infections and infestations | ||||||||
| Oral candidiasis | 0/6 (0%) | 0 | 2/12 (16.7%) | 2 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Skin candida | 1/6 (16.7%) | 1 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Cellulitis | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Conjunctivitis | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Dermatitis infected | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 1/4 (25%) | 1 |
| Fungal infection | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Furuncle | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Lower respiratory tract infection | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Skin abrasion | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||
| Fall | 1/6 (16.7%) | 1 | 1/12 (8.3%) | 1 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Arthropod bite | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Laceration | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Muscle strain | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Post procedural complication | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Post procedural discharge | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Sunburn | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Investigations | ||||||||
| Blood creatinine increased | 4/6 (66.7%) | 4 | 1/12 (8.3%) | 1 | 1/6 (16.7%) | 1 | 1/4 (25%) | 1 |
| Electrocardiogram QT prolonged | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 2/6 (33.3%) | 2 | 0/4 (0%) | 0 |
| Weight decreased | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 1/6 (16.7%) | 1 | 1/4 (25%) | 1 |
| Alanine aminotransferase increased | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Aspartate aminotransferase increased | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Blood sodium decreased | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 1/4 (25%) | 1 |
| White blood cell count decreased | 0/6 (0%) | 0 | 2/12 (16.7%) | 2 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Blood alkaline phosphatase increased | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Blood bilirubin increased | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Blood glucose increased | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Blood iron decreased | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Blood phosphorus decreased | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Blood potassium decreased | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Blood thyroid stimulating hormone increased | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Cardiac murmur | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Lymphocyte count decreased | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Neutrophil count decreased | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Troponin increased | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||
| Hypoalbuminaemia | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 3/6 (50%) | 3 | 1/4 (25%) | 1 |
| Decreased appetite | 1/6 (16.7%) | 1 | 2/12 (16.7%) | 2 | 0/6 (0%) | 0 | 1/4 (25%) | 1 |
| Hypophosphataemia | 1/6 (16.7%) | 1 | 1/12 (8.3%) | 1 | 1/6 (16.7%) | 1 | 1/4 (25%) | 1 |
| Hypokalaemia | 1/6 (16.7%) | 1 | 1/12 (8.3%) | 1 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Dehydration | 2/6 (33.3%) | 2 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Hyperglycaemia | 2/6 (33.3%) | 2 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Hypermagnesaemia | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Hyponatraemia | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Hyperkalaemia | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Hypocalcaemia | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Myalgia | 2/6 (33.3%) | 2 | 4/12 (33.3%) | 4 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Arthralgia | 1/6 (16.7%) | 1 | 3/12 (25%) | 3 | 1/6 (16.7%) | 1 | 1/4 (25%) | 1 |
| Pain in extremity | 1/6 (16.7%) | 1 | 3/12 (25%) | 3 | 2/6 (33.3%) | 2 | 0/4 (0%) | 0 |
| Neck pain | 1/6 (16.7%) | 1 | 2/12 (16.7%) | 2 | 0/6 (0%) | 0 | 1/4 (25%) | 1 |
| Musculoskeletal pain | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 1/4 (25%) | 1 |
| Back pain | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Muscle spasms | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Musculoskeletal chest pain | 0/6 (0%) | 0 | 2/12 (16.7%) | 2 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Musculoskeletal stiffness | 1/6 (16.7%) | 1 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Flank pain | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Groin pain | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Joint swelling | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Muscular weakness | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Osteoporosis | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Periarthritis | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Acrochordon | 0/6 (0%) | 0 | 2/12 (16.7%) | 2 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Melanocytic naevus | 1/6 (16.7%) | 1 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Skin papilloma | 1/6 (16.7%) | 1 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Squamous cell carcinoma of skin | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Acanthoma | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Infected neoplasm | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Neoplasm | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Seborrhoeic keratosis | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Nervous system disorders | ||||||||
| Headache | 0/6 (0%) | 0 | 2/12 (16.7%) | 2 | 1/6 (16.7%) | 1 | 1/4 (25%) | 1 |
| Dysgeusia | 2/6 (33.3%) | 2 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Dizziness | 0/6 (0%) | 0 | 2/12 (16.7%) | 2 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Neuralgia | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Peripheral sensory neuropathy | 1/6 (16.7%) | 1 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Somnolence | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 2/6 (33.3%) | 2 | 0/4 (0%) | 0 |
| Balance disorder | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Hyperaesthesia | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Hypoaesthesia | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Neuropathy peripheral | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Paraesthesia | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Partial seizures | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Peripheral motor neuropathy | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Sciatica | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Syncope | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 1/4 (25%) | 1 |
| Psychiatric disorders | ||||||||
| Insomnia | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 1/4 (25%) | 1 |
| Mood swings | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Anger | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Confusional state | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Irritability | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Mental status changes | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Sleep disorder | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Renal and urinary disorders | ||||||||
| Acute kidney injury | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Dysuria | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Renal impairment | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Urinary retention | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||
| Penile oedema | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Scrotal oedema | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Scrotal pain | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Scrotal swelling | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Oropharyngeal pain | 0/6 (0%) | 0 | 2/12 (16.7%) | 2 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Cough | 1/6 (16.7%) | 1 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Dyspnoea | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Pulmonary embolism | 1/6 (16.7%) | 1 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Rhinorrhoea | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Dry throat | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Dysphonia | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Dyspnoea exertional | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Pleural effusion | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Upper-airway cough syndrome | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Wheezing | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||
| Palmar-plantar erythrodysaesthesia syndrome | 2/6 (33.3%) | 2 | 7/12 (58.3%) | 7 | 3/6 (50%) | 3 | 1/4 (25%) | 1 |
| Pruritus | 2/6 (33.3%) | 2 | 7/12 (58.3%) | 7 | 1/6 (16.7%) | 1 | 2/4 (50%) | 2 |
| Alopecia | 3/6 (50%) | 3 | 2/12 (16.7%) | 2 | 1/6 (16.7%) | 1 | 1/4 (25%) | 1 |
| Dry skin | 1/6 (16.7%) | 1 | 4/12 (33.3%) | 4 | 2/6 (33.3%) | 2 | 0/4 (0%) | 0 |
| Rash | 4/6 (66.7%) | 4 | 2/12 (16.7%) | 2 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Rash maculo-papular | 0/6 (0%) | 0 | 2/12 (16.7%) | 2 | 0/6 (0%) | 0 | 2/4 (50%) | 2 |
| Hyperkeratosis | 0/6 (0%) | 0 | 2/12 (16.7%) | 2 | 0/6 (0%) | 0 | 2/4 (50%) | 2 |
| Dermatitis acneiform | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 1/4 (25%) | 1 |
| Erythema | 1/6 (16.7%) | 1 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Hyperhidrosis | 0/6 (0%) | 0 | 2/12 (16.7%) | 2 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Night sweats | 0/6 (0%) | 0 | 2/12 (16.7%) | 2 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Palmoplantar keratoderma | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Photosensitivity reaction | 0/6 (0%) | 0 | 2/12 (16.7%) | 2 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Pruritus generalised | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 1/4 (25%) | 1 |
| Skin exfoliation | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Skin hyperpigmentation | 1/6 (16.7%) | 1 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Skin sensitisation | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Transient acantholytic dermatosis | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Actinic keratosis | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Cold sweat | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Ephelides | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Intertrigo | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Leukoplakia | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Pain of skin | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Psoriasis | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Rash erythematous | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Rash papular | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 |
| Rash pruritic | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Skin hypopigmentation | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Skin lesion | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Vitiligo | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Vascular disorders | ||||||||
| Flushing | 3/6 (50%) | 3 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 1/4 (25%) | 1 |
| Hot flush | 0/6 (0%) | 0 | 2/12 (16.7%) | 2 | 0/6 (0%) | 0 | 1/4 (25%) | 1 |
| Hypotension | 0/6 (0%) | 0 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 2/4 (50%) | 2 |
| Embolism | 0/6 (0%) | 0 | 1/12 (8.3%) | 1 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
| Hypertension | 1/6 (16.7%) | 1 | 0/12 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 |
Limitations/Caveats
Study recruitment was halted on 07-Aug-2014 during the Phase Ib part of the study. The Phase II part of the study was not performed. Early termination of the study was not due to any safety concerns.
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 trial.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Array BioPharma, Inc. |
| Phone | 303-381-6604 |
| info@arraybiopharma.com |
Responsible Party:
Array BioPharma
ClinicalTrials.gov Identifier:
NCT01777776
Other Study ID Numbers:
- CLEE011X2105
First Posted:
Jan 29, 2013
Last Update Posted:
Sep 13, 2016
Last Verified:
Jul 1, 2016