A Phase Ib/II Study of AEB071 and MEK162 in Adult Patients With Metastatic Uveal Melanoma
Sponsor
Array Biopharma, now a wholly owned subsidiary of Pfizer (Industry)
Overall Status
Terminated
CT.gov ID
NCT01801358
Collaborator
(none)
38
7
2
21
5.4
0.3
Study Details
Study Description
Brief Summary
A phase Ib dose-escalation study of the AEB071 and MEK162 combination in adult patients with confirmed metastatic uveal melanoma. Cohorts of 3-6 patients will be assessed for dose limiting toxicities (DLTs) during Cycle 1 until the maximum tolerated dose (MTD) of the combination therapy is determined. The MTD or Phase 2 Recommended Dose (P2RD) will be used in a Phase II part of the study, which will enrol 55 patients each into two randomized groups: the combination therapy or MEK162 alone. The Phase II part will continue until proof of concept is established. Patients will continue treatment as long as clinical benefit is seen and no limiting adverse toxicity is observed
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Detailed Description
Due to halted enrollment, the Phase II part of the study was not conducted. The Sponsor decided to permanently stop recruitment for the study prior to MTD determination.
Remaining patients on treatment with binimetinib and sotrastaurin who were considered by the Investigator to be benefiting from their treatment could have continued treatment and were to be followed up as per protocol. No patients were ongoing as of the data cut-off date. After the last patient last visit (LPLV) was declared, the study was terminated.
Study Design
Study Type:
Interventional
Actual Enrollment
:
38 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase Ib/II, Open-label, Multicenter Study of AEB071 and MEK162 in Adult Patients With Metastatic Uveal Melanoma
Study Start Date
:
Aug 1, 2013
Actual Primary Completion Date
:
May 1, 2015
Actual Study Completion Date
:
May 1, 2015
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Arm A AEB071 and MEK162 combined |
Drug: AEB071
Twice-daily doses of AEB071 for a cycle of 28-days, given without interruption (continuous cycles)
Other Names:
Drug: MEK162
Twice-daily doses of MEK162 for a cycle of 28-days, given without interruption (continuous cycles)
|
| Experimental: Arm B MEK162 alone |
Drug: MEK162
Twice-daily doses of MEK162 for a cycle of 28-days, given without interruption (continuous cycles)
|
Outcome Measures
Primary Outcome Measures
- Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle [Cycle 1 (up to 28 days)]
A DLT is defined as an adverse event or abnormal laboratory value as defined in the protocol that is assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first 28 days of treatment with AEB071 and MEK162.
- Phase II: Progression Free Survival (PFS) [From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit)]
The time from date of randomization to the date of event defined as the first documented progression or death due to any cause. Due to an enrollment halt, the Phase II part of the study was not conducted. The sponsor decided to permanently stop recruitment for the study prior to MTD determination.
Secondary Outcome Measures
- Phase Ib/II: The Number of Subjects Experiencing At Least One Adverse Event (AE) [From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit)]
An adverse event 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.
- Phase Ib/II: The Number of Subjects Experiencing At Least One Serious Adverse Event (SAE) [From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit)]
Serious adverse event (SAE) is defined as one of the following: Is fatal or life-threatening Results in persistent or significant disability/incapacity Constitutes a congenital anomaly/birth defect Is medically significant Requires inpatient hospitalization or prolongation of existing hospitalization Note that hospitalizations for the following reasons should not be reported as serious adverse events: Routine treatment or monitoring of the studied indication, not associated with any deterioration in condition Elective or pre-planned treatment for a pre-existing condition that is unrelated to metastatic uveal melanoma and has not worsened since signing the informed consent Social reasons and respite care in the absence of any deterioration in the patient's general condition
- Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Best Overall Response (BOR) [Cycle 1 (up to 28 days)]
Assessment of the preliminary anti-tumor activity of AEB071 and MEK162 in combination. The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for PD the smallest measurements recorded since the treatment started). In general, the patient's best response assignment will depend on the achievement of both measurement and confirmation criteria.
- Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Duration of Response (DOR) [Cycle 1 (up to 28 days)]
Assessment of the preliminary anti-tumor activity of AEB071 and MEK162 in combination. Duration of Response (DOR) is not reported, since there were no responses of Complete Response (CR) or Partial Response (PR) at any time during the study.
- Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Progression Free Survival (PFS) [Cycle 1 (up to 28 days)]
Assessment of the preliminary anti-tumor activity of AEB071 and MEK162 in combination. 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.
- Phase II: Evaluation of Preliminary Anti-tumor Activity - Overall Response Rate (CR+PR) [From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit)]
Evaluation of the preliminary anti-tumor activity at the RP2D for AEB071 and MEK162 and at 45 mg BID for MEK162 alone. Overall response rate (ORR) is the proportion of patients with a best overall response of Complete Response (CR) or Partial Response (PR). This is also referred to as 'Objective response rate' in some protocols or publications. Due to an enrollment halt, the Phase II part of the study was not conducted.
- Phase II: Evaluation of Preliminary Anti-tumor Activity - Best Overall Response (BOR) [From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit)]
Evaluation of the preliminary anti-tumor activity at the RP2D for AEB071 and MEK162 and at 45 mg BID for MEK162 alone. The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for Progressive Disease (PD) the smallest measurements recorded since the treatment started). In general, the patient's best response assignment will depend on the achievement of both measurement and confirmation criteria. Due to an enrollment halt, the Phase II part of the study was not conducted.
- Phase II: Evaluation of Preliminary Anti-tumor Activity - Duration of Response (DOR) [From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit)]
Evaluation of the preliminary anti-tumor activity at the RP2D for AEB071 and MEK162 and at 45 mg BID for MEK162 alone. Duration of Response is not reported, due to the enrollment halt, which occurred prior to Phase II of the study.
- Phase II: Evaluation of Preliminary Anti-tumor Activity - Overall Survival (OS) [From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit)]
Evaluation of the preliminary anti-tumor activity at the RP2D for AEB071 and MEK162 and at 45 mg BID for MEK162 alone. Overall survival (OS) is defined as the time from date of randomization/start of treatment to date of death due to any cause. Due to an enrollment halt, the Phase II part of the study was not conducted.
- Phase Ib: PK Parameters for AEB071 - AUC0-8hr (Cycle 1; Day 1) [Cycle 1 (Day 1)]
Blood samples were collected from all patients during Cycle 1 (Days 1 and 15) for pharmacokinetic profiling. On Days 8 and 22 of Cycle 1, trough samples were collected. Additionally, pre-dose samples were collected on Day 1 of Cycle 2 through Cycle 6.
- Phase lb: PK Parameters for AEB071 - Cmax (Cycle 1; Day 1) [Cycle 1 (Day 1)]
Blood samples were collected from all patients during Cycle 1 (Days 1 and 15) for pharmacokinetic profiling. On Days 8 and 22 of Cycle 1, trough samples were collected. Additionally, pre-dose samples were collected on Day 1 of Cycle 2 through Cycle 6.
- Phase lb: PK Parameters for AEB071 - Tmax (Cycle 1; Day 1) [Cycle 1 (Day 1)]
Blood samples were collected from all patients during Cycle 1 (Days 1 and 15) for pharmacokinetic profiling. On Days 8 and 22 of Cycle 1, trough samples were collected. Additionally, pre-dose samples were collected on Day 1 of Cycle 2 through Cycle 6.
- Phase Ib: PK Parameters for AEB071 - AUC0-8hr (Cycle 1; Day 15) [Cycle 1 (Day 15)]
Blood samples were collected from all patients during Cycle 1 (Days 1 and 15) for pharmacokinetic profiling. On Days 8 and 22 of Cycle 1, trough samples were collected. Additionally, pre-dose samples were collected on Day 1 of Cycle 2 through Cycle 6.
- Phase lb: PK Parameters for AEB071 - Cmax (Cycle 1; Day 15) [Cycle 1 (Day 15)]
Blood samples were collected from all patients during Cycle 1 (Days 1 and 15) for pharmacokinetic profiling. On Days 8 and 22 of Cycle 1, trough samples were collected. Additionally, pre-dose samples were collected on Day 1 of Cycle 2 through Cycle 6.
- Phase lb: PK Parameters for AEB071 - Tmax (Cycle 1; Day 15) [Cycle 1 (Day 15)]
Blood samples were collected from all patients during Cycle 1 (Days 1 and 15) for pharmacokinetic profiling. On Days 8 and 22 of Cycle 1, trough samples were collected. Additionally, pre-dose samples were collected on Day 1 of Cycle 2 through Cycle 6.
- Phase Ib: PK Parameters for MEK162 - AUC0-8hr (Cycle 1; Day 1) [Cycle 1 (Day 1)]
Blood samples were collected from all patients during Cycle 1 (Days 1 and 15) for pharmacokinetic profiling. On Days 8 and 22 of Cycle 1, trough samples were collected. Additionally, pre-dose samples were collected on Day 1 of Cycle 2 through Cycle 6.
- Phase lb: PK Parameters for MEK162 - Cmax (Cycle 1; Day 1) [Cycle 1 (Day 1)]
Blood samples were collected from all patients during Cycle 1 (Days 1 and 15) for pharmacokinetic profiling. On Days 8 and 22 of Cycle 1, trough samples were collected. Additionally, pre-dose samples were collected on Day 1 of Cycle 2 through Cycle 6.
- Phase lb: PK Parameters for MEK162 - Tmax (Cycle 1; Day 1) [Cycle 1 (Day 1)]
Blood samples were collected from all patients during Cycle 1 (Days 1 and 15) for pharmacokinetic profiling. On Days 8 and 22 of Cycle 1, trough samples were collected. Additionally, pre-dose samples were collected on Day 1 of Cycle 2 through Cycle 6.
- Phase Ib: PK Parameters for MEK162 - AUC0-8hr (Cycle 1; Day 15) [Cycle 1 (Day 15)]
Blood samples were collected from all patients during Cycle 1 (Days 1 and 15) for pharmacokinetic profiling. On Days 8 and 22 of Cycle 1, trough samples were collected. Additionally, pre-dose samples were collected on Day 1 of Cycle 2 through Cycle 6.
- Phase lb: PK Parameters for MEK162 - Cmax (Cycle 1; Day 15) [Cycle 1 (Day 15)]
Blood samples were collected from all patients during Cycle 1 (Days 1 and 15) for pharmacokinetic profiling. On Days 8 and 22 of Cycle 1, trough samples were collected. Additionally, pre-dose samples were collected on Day 1 of Cycle 2 through Cycle 6.
- Phase lb: PK Parameters for MEK162 - Tmax (Cycle 1; Day 15) [Cycle 1 (Day 15)]
Blood samples were collected from all patients during Cycle 1 (Days 1 and 15) for pharmacokinetic profiling. On Days 8 and 22 of Cycle 1, trough samples were collected. Additionally, pre-dose samples were collected on Day 1 of Cycle 2 through Cycle 6.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Written informed consent
-
Male and female patients aged 18 years or older
-
A history of uveal (ocular) melanoma with biopsy-confirmed metastatic disease
-
Consent to providing 3 tumor biopsy samples throughout the course of the study
-
Presence of measurable disease
-
A WHO performance status of less than or equal to 1
Exclusion Criteria:
-
Presence of CNS lesions (stable lesions may be acceptable)
-
Previous or concurrent malignancy, other than basal cell or squamous cell carcinoma of the skin: in situ carcinoma of the cervix, without evidence of recurrence for at least 3 years; a primary malignancy completely resected and no evidence of recurrence for at least 3 years
-
Adverse event from prior chemotherapy, radiotherapy or surgery that has not recovered to CTCAE v4.03 Grade 1 or less, except for alopecia/sensory peripheral neuropathy, which must be less than Grade 2
-
History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO
-
Impaired cardiac function or clinically significant cardiac disease
-
Impaired GI function or disease that could interfere with the absorption of AEB071 and/or MEK162
-
Treatment with medicines or herbal supplements that are known inhibitors or inducers of CYP3A4/5 and cannot be withdrawn prior to study treatment
-
Females of child-bearing potential who are unwilling or unable to use highly effective means of contraception
-
Males who are unwilling or unable to use a condom during sexual intercourse
-
Prior exposure to a MEK or PKC inhibitor Other inclusion/exclusion criteria apply
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Dana Farber Cancer Institute Dept. Onc | Boston | Massachusetts | United States | 02215 |
| 2 | Memorial Sloan Kettering Cancer Center Dept of Onc.. | New York | New York | United States | 90033 |
| 3 | Pfizer Investigative Site | Paris | France | 75231 | |
| 4 | Pfizer Investigative Site | Essen | Germany | 45147 | |
| 5 | Pfizer Investigative Site | Leiden | Netherlands | 2300 RC | |
| 6 | Pfizer Investigative Site | Madrid | Spain | 28050 | |
| 7 | Pfizer Investigative Site | London | United Kingdom | SW3 6JJ |
Sponsors and Collaborators
- Array Biopharma, now a wholly owned subsidiary of Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Array Biopharma, now a wholly owned subsidiary of Pfizer
ClinicalTrials.gov Identifier:
NCT01801358
Other Study ID Numbers:
- CMEK162X2203
First Posted:
Feb 28, 2013
Last Update Posted:
Sep 16, 2020
Last Verified:
Sep 1, 2020
Keywords provided by Array Biopharma, now a wholly owned subsidiary of Pfizer
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | The CMEK162X2203 study began recruitment on 26-Aug-2013 and concluded on 15-May-2015. Due to an enrollment halt, the Phase II part of the study was not conducted. The sponsor decided to permanently stop recruitment for the study prior to MTD determination. |
|---|---|
| Pre-assignment Detail | Participant Flow and Baseline Demographics data represents the Full Analysis Set (FAS), which includes all patients who received at least one full or partial dose of sotrastaurin or binimetinib. Not completed subjects represents subjects that stopped treatment early, due to the corresponding reason. |
| Arm/Group Title | Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (FAS) | Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (FAS) | Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (FAS) | Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (FAS) | Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (FAS) | Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (FAS) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. |
| Period Title: Overall Study | ||||||
| STARTED | 6 | 6 | 6 | 6 | 6 | 8 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 6 | 6 | 6 | 6 | 6 | 8 |
Baseline Characteristics
| Arm/Group Title | Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (FAS) | Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (FAS) | Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (FAS) | Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (FAS) | Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (FAS) | Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (FAS) | Total |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Total of all reporting groups |
| Overall Participants | 6 | 6 | 6 | 6 | 6 | 8 | 38 |
| Age (Count of Participants) | |||||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
5
83.3%
|
5
83.3%
|
5
83.3%
|
3
50%
|
4
66.7%
|
5
62.5%
|
27
71.1%
|
| >=65 years |
1
16.7%
|
1
16.7%
|
1
16.7%
|
3
50%
|
2
33.3%
|
3
37.5%
|
11
28.9%
|
| Age (years) [Mean (Standard Deviation) ] | |||||||
| Mean (Standard Deviation) [years] |
48.7
(15.21)
|
57.0
(10.43)
|
52.8
(10.82)
|
59.8
(9.11)
|
56.8
(10.87)
|
61.5
(10.65)
|
56.4
(11.39)
|
| Sex: Female, Male (Count of Participants) | |||||||
| Female |
3
50%
|
2
33.3%
|
3
50%
|
2
33.3%
|
2
33.3%
|
2
25%
|
14
36.8%
|
| Male |
3
50%
|
4
66.7%
|
3
50%
|
4
66.7%
|
4
66.7%
|
6
75%
|
24
63.2%
|
| Race/Ethnicity, Customized (participants) [Number] | |||||||
| Hispanic or Latino |
1
16.7%
|
1
16.7%
|
2
33.3%
|
1
16.7%
|
1
16.7%
|
0
0%
|
6
15.8%
|
| Russian |
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
2.6%
|
| Unknown |
2
33.3%
|
4
66.7%
|
2
33.3%
|
1
16.7%
|
1
16.7%
|
0
0%
|
10
26.3%
|
| Other |
2
33.3%
|
1
16.7%
|
2
33.3%
|
4
66.7%
|
4
66.7%
|
8
100%
|
21
55.3%
|
| Region of Enrollment (participants) [Number] | |||||||
| Netherlands |
0
0%
|
0
0%
|
1
16.7%
|
1
16.7%
|
1
16.7%
|
2
25%
|
5
13.2%
|
| United States |
1
16.7%
|
0
0%
|
2
33.3%
|
2
33.3%
|
2
33.3%
|
0
0%
|
7
18.4%
|
| United Kingdom |
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
2
5.3%
|
| France |
2
33.3%
|
3
50%
|
1
16.7%
|
1
16.7%
|
0
0%
|
0
0%
|
7
18.4%
|
| Germany |
2
33.3%
|
1
16.7%
|
0
0%
|
1
16.7%
|
1
16.7%
|
6
75%
|
11
28.9%
|
| Spain |
1
16.7%
|
1
16.7%
|
2
33.3%
|
1
16.7%
|
1
16.7%
|
0
0%
|
6
15.8%
|
| Baseline WHO Performance Status (participants) [Number] | |||||||
| 0: |
3
50%
|
6
100%
|
5
83.3%
|
5
83.3%
|
5
83.3%
|
8
100%
|
32
84.2%
|
| 1: |
3
50%
|
0
0%
|
1
16.7%
|
1
16.7%
|
1
16.7%
|
0
0%
|
6
15.8%
|
Outcome Measures
| Title | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle |
|---|---|
| Description | A DLT is defined as an adverse event or abnormal laboratory value as defined in the protocol that is assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first 28 days of treatment with AEB071 and MEK162. |
| Time Frame | Cycle 1 (up to 28 days) |
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 Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (DDS) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. |
| Measure Participants | 6 | 6 | 5 | 6 | 6 | 4 |
| Anaemia |
0
|
0
|
0
|
1
|
0
|
0
|
| Diarrhoea |
0
|
0
|
2
|
1
|
0
|
0
|
| Vomiting |
0
|
0
|
0
|
1
|
1
|
1
|
| Nausea |
0
|
0
|
0
|
1
|
0
|
1
|
| Fatigue |
0
|
0
|
1
|
1
|
0
|
0
|
| General Physical Health Deterioration |
0
|
0
|
1
|
0
|
0
|
0
|
| Malaise |
0
|
0
|
0
|
1
|
0
|
0
|
| Blood Creatinine Increased |
0
|
0
|
0
|
0
|
1
|
0
|
| Ejection Fraction Decreased |
0
|
0
|
0
|
0
|
0
|
1
|
| Dermatitis Acneiform |
0
|
2
|
0
|
0
|
0
|
0
|
| Rash |
0
|
0
|
0
|
1
|
0
|
0
|
| Title | Phase II: Progression Free Survival (PFS) |
|---|---|
| Description | The time from date of randomization to the date of event defined as the first documented progression or death due to any cause. Due to an enrollment halt, the Phase II part of the study was not conducted. The sponsor decided to permanently stop recruitment for the study prior to MTD determination. |
| Time Frame | From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Phase II (Dose Expansion) |
|---|---|
| Arm/Group Description | Following the determination of the maximum tolerated dose (MTD) or the recommended phase two dose (RP2D), patients would have been randomized into two arms in a 1:1 ratio, to receive AEB071 and MEK162 or MEK162 alone. However, due to an enrollment halt, the Phase II part of the study did not occur. |
| Measure Participants | 0 |
| Title | Phase Ib/II: The Number of Subjects Experiencing At Least One Adverse Event (AE) |
|---|---|
| Description | An adverse event 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. |
| Time Frame | From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis group consists of the Safety Set (SS), which is all patients who received at least one dose of AEB071 and MEK162, and have at least one valid post-baseline safety assessment. |
| Arm/Group Title | Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (SS) | Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (SS) | Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (SS) | Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (SS) | Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (SS) | Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (SS) | Phase II (Dose Expansion) |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Following the determination of the maximum tolerated dose (MTD) or the recommended phase two dose (RP2D), patients would have been randomized into two arms in a 1:1 ratio, to receive AEB071 and MEK162 or MEK162 alone. However, due to an enrollment halt, the Phase II part of the study did not occur. |
| Measure Participants | 6 | 6 | 6 | 6 | 6 | 8 | 0 |
| Number [participants] |
6
100%
|
6
100%
|
6
100%
|
6
100%
|
6
100%
|
8
100%
|
| Title | Phase Ib/II: The Number of Subjects Experiencing At Least One Serious Adverse Event (SAE) |
|---|---|
| Description | Serious adverse event (SAE) is defined as one of the following: Is fatal or life-threatening Results in persistent or significant disability/incapacity Constitutes a congenital anomaly/birth defect Is medically significant Requires inpatient hospitalization or prolongation of existing hospitalization Note that hospitalizations for the following reasons should not be reported as serious adverse events: Routine treatment or monitoring of the studied indication, not associated with any deterioration in condition Elective or pre-planned treatment for a pre-existing condition that is unrelated to metastatic uveal melanoma and has not worsened since signing the informed consent Social reasons and respite care in the absence of any deterioration in the patient's general condition |
| Time Frame | From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit) |
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 AEB071 and MEK162, and have at least one valid post-baseline safety assessment. |
| Arm/Group Title | Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (SS) | Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (SS) | Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (SS) | Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (SS) | Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (SS) | Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (SS) | Phase II (Dose Expansion) |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Following the determination of the maximum tolerated dose (MTD) or the recommended phase two dose (RP2D), patients would have been randomized into two arms in a 1:1 ratio, to receive AEB071 and MEK162 or MEK162 alone. However, due to an enrollment halt, the Phase II part of the study did not occur. |
| Measure Participants | 6 | 6 | 6 | 6 | 6 | 8 | 0 |
| Number [participants] |
3
50%
|
1
16.7%
|
3
50%
|
4
66.7%
|
2
33.3%
|
6
75%
|
| Title | Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Best Overall Response (BOR) |
|---|---|
| Description | Assessment of the preliminary anti-tumor activity of AEB071 and MEK162 in combination. The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for PD the smallest measurements recorded since the treatment started). In general, the patient's best response assignment will depend on the achievement of both measurement and confirmation criteria. |
| Time Frame | Cycle 1 (up to 28 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis group is comprised of the Full Analysis Set (FAS), which is all patients in the phase Ib part of the study who received at least one full or partial dose of AEB071 or MEK162. |
| Arm/Group Title | Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (FAS) | Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (FAS) | Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (FAS) | Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (FAS) | Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (FAS) | Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (FAS) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. |
| Measure Participants | 6 | 6 | 6 | 6 | 6 | 8 |
| Complete Response |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Partial Response |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Stable Disease |
5
83.3%
|
4
66.7%
|
4
66.7%
|
2
33.3%
|
3
50%
|
5
62.5%
|
| Progressive disease |
1
16.7%
|
2
33.3%
|
1
16.7%
|
2
33.3%
|
3
50%
|
2
25%
|
| Unknown |
0
0%
|
0
0%
|
1
16.7%
|
2
33.3%
|
0
0%
|
1
12.5%
|
| Title | Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Duration of Response (DOR) |
|---|---|
| Description | Assessment of the preliminary anti-tumor activity of AEB071 and MEK162 in combination. Duration of Response (DOR) is not reported, since there were no responses of Complete Response (CR) or Partial Response (PR) at any time during the study. |
| Time Frame | Cycle 1 (up to 28 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis group is comprised of the Full Analysis Set (FAS), which is all patients in the phase Ib part of the study who received at least one full or partial dose of AEB071 or MEK162. |
| Arm/Group Title | Phase Ib (Dose Escalation) |
|---|---|
| Arm/Group Description | For Phase Ib, a minimum of three patients will be entered into each cohort and evaluated for safety (DLTs and any other medically significant event) at the end of Cycle 1. Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. |
| Measure Participants | 0 |
| Title | Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Progression Free Survival (PFS) |
|---|---|
| Description | Assessment of the preliminary anti-tumor activity of AEB071 and MEK162 in combination. 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. |
| Time Frame | Cycle 1 (up to 28 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis group is comprised of the Full Analysis Set (FAS), which is all patients in the phase Ib part of the study who received at least one full or partial dose of AEB071 or MEK162. |
| Arm/Group Title | Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (FAS) | Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (FAS) | Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (FAS) | Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (FAS) | Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (FAS) | Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (FAS) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. |
| Measure Participants | 6 | 6 | 6 | 6 | 6 | 8 |
| Median (Inter-Quartile Range) [weeks] |
3.6
|
3.4
|
4
|
3.7
|
3.1
|
3.8
|
| Title | Phase II: Evaluation of Preliminary Anti-tumor Activity - Overall Response Rate (CR+PR) |
|---|---|
| Description | Evaluation of the preliminary anti-tumor activity at the RP2D for AEB071 and MEK162 and at 45 mg BID for MEK162 alone. Overall response rate (ORR) is the proportion of patients with a best overall response of Complete Response (CR) or Partial Response (PR). This is also referred to as 'Objective response rate' in some protocols or publications. Due to an enrollment halt, the Phase II part of the study was not conducted. |
| Time Frame | From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis group is comprised of the Full Analysis Set (FAS), which is all patients in the phase Ib part of the study who received at least one full or partial dose of AEB071 or MEK162. |
| Arm/Group Title | Phase II (Dose Expansion) |
|---|---|
| Arm/Group Description | Following the determination of the maximum tolerated dose (MTD) or the recommended phase two dose (RP2D), patients would have been randomized into two arms in a 1:1 ratio, to receive AEB071 and MEK162 or MEK162 alone. However, due to an enrollment halt, the Phase II part of the study did not occur. |
| Measure Participants | 0 |
| Title | Phase II: Evaluation of Preliminary Anti-tumor Activity - Best Overall Response (BOR) |
|---|---|
| Description | Evaluation of the preliminary anti-tumor activity at the RP2D for AEB071 and MEK162 and at 45 mg BID for MEK162 alone. The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for Progressive Disease (PD) the smallest measurements recorded since the treatment started). In general, the patient's best response assignment will depend on the achievement of both measurement and confirmation criteria. Due to an enrollment halt, the Phase II part of the study was not conducted. |
| Time Frame | From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis group is comprised of the Full Analysis Set (FAS), which is all patients in the phase Ib part of the study who received at least one full or partial dose of AEB071 or MEK162. |
| Arm/Group Title | Phase II (Dose Expansion) |
|---|---|
| Arm/Group Description | Following the determination of the maximum tolerated dose (MTD) or the recommended phase two dose (RP2D), patients would have been randomized into two arms in a 1:1 ratio, to receive AEB071 and MEK162 or MEK162 alone. However, due to an enrollment halt, the Phase II part of the study did not occur. |
| Measure Participants | 0 |
| Title | Phase II: Evaluation of Preliminary Anti-tumor Activity - Duration of Response (DOR) |
|---|---|
| Description | Evaluation of the preliminary anti-tumor activity at the RP2D for AEB071 and MEK162 and at 45 mg BID for MEK162 alone. Duration of Response is not reported, due to the enrollment halt, which occurred prior to Phase II of the study. |
| Time Frame | From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis group is comprised of the Full Analysis Set (FAS), which is all patients in the phase Ib part of the study who received at least one full or partial dose of AEB071 or MEK162. |
| Arm/Group Title | Phase II (Dose Expansion) |
|---|---|
| Arm/Group Description | Following the determination of the maximum tolerated dose (MTD) or the recommended phase two dose (RP2D), patients would have been randomized into two arms in a 1:1 ratio, to receive AEB071 and MEK162 or MEK162 alone. However, due to an enrollment halt, the Phase II part of the study did not occur. |
| Measure Participants | 0 |
| Title | Phase II: Evaluation of Preliminary Anti-tumor Activity - Overall Survival (OS) |
|---|---|
| Description | Evaluation of the preliminary anti-tumor activity at the RP2D for AEB071 and MEK162 and at 45 mg BID for MEK162 alone. Overall survival (OS) is defined as the time from date of randomization/start of treatment to date of death due to any cause. Due to an enrollment halt, the Phase II part of the study was not conducted. |
| Time Frame | From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis group is comprised of the Full Analysis Set (FAS), which is all patients in the phase Ib part of the study who received at least one full or partial dose of AEB071 or MEK162. |
| Arm/Group Title | Phase II (Dose Expansion) |
|---|---|
| Arm/Group Description | Following the determination of the maximum tolerated dose (MTD) or the recommended phase two dose (RP2D), patients would have been randomized into two arms in a 1:1 ratio, to receive AEB071 and MEK162 or MEK162 alone. However, due to an enrollment halt, the Phase II part of the study did not occur. |
| Measure Participants | 0 |
| Title | Phase Ib: PK Parameters for AEB071 - AUC0-8hr (Cycle 1; Day 1) |
|---|---|
| Description | Blood samples were collected from all patients during Cycle 1 (Days 1 and 15) for pharmacokinetic profiling. On Days 8 and 22 of Cycle 1, trough samples were collected. Additionally, pre-dose samples were collected on Day 1 of Cycle 2 through Cycle 6. |
| Time Frame | Cycle 1 (Day 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| This analysis group is comprised of the Pharmacokinetic Analysis Set (PAS), which is all patients who have evaluable pharmacokinetic (PK) data. The PAS will be used for summaries (tables and figures) and listings of PK data. |
| Arm/Group Title | Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (PAS) | Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (PAS) | Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (PAS) | Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (PAS) | Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (PAS) | Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (PAS) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. |
| Measure Participants | 6 | 5 | 6 | 6 | 4 | 8 |
| Geometric Mean (Geometric Coefficient of Variation) [hr*ng/ml] |
7448.5
(46.34)
|
7136
(25.09)
|
15090
(53.89)
|
14051.2
(45.83)
|
18840.8
(36.24)
|
15217.1
(71.48)
|
| Title | Phase lb: PK Parameters for AEB071 - Cmax (Cycle 1; Day 1) |
|---|---|
| Description | Blood samples were collected from all patients during Cycle 1 (Days 1 and 15) for pharmacokinetic profiling. On Days 8 and 22 of Cycle 1, trough samples were collected. Additionally, pre-dose samples were collected on Day 1 of Cycle 2 through Cycle 6. |
| Time Frame | Cycle 1 (Day 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| This analysis group is comprised of the Pharmacokinetic Analysis Set (PAS), which is all patients who have evaluable pharmacokinetic (PK) data. The PAS will be used for summaries (tables and figures) and listings of PK data. |
| Arm/Group Title | Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (PAS) | Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (PAS) | Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (PAS) | Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (PAS) | Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (PAS) | Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (PAS) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. |
| Measure Participants | 6 | 5 | 6 | 6 | 4 | 8 |
| Geometric Mean (Geometric Coefficient of Variation) [ng/ml] |
1837.5
(35.9)
|
1932.5
(31.18)
|
2968.1
(58.32)
|
2813
(36.83)
|
4459
(26.45)
|
3768.7
(57.12)
|
| Title | Phase lb: PK Parameters for AEB071 - Tmax (Cycle 1; Day 1) |
|---|---|
| Description | Blood samples were collected from all patients during Cycle 1 (Days 1 and 15) for pharmacokinetic profiling. On Days 8 and 22 of Cycle 1, trough samples were collected. Additionally, pre-dose samples were collected on Day 1 of Cycle 2 through Cycle 6. |
| Time Frame | Cycle 1 (Day 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| This analysis group is comprised of the Pharmacokinetic Analysis Set (PAS), which is all patients who have evaluable pharmacokinetic (PK) data. The PAS will be used for summaries (tables and figures) and listings of PK data. |
| Arm/Group Title | Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (PAS) | Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (PAS) | Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (PAS) | Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (PAS) | Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (PAS) | Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (PAS) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. |
| Measure Participants | 6 | 5 | 6 | 6 | 4 | 8 |
| Median (Full Range) [hr] |
1.6
|
1.1
|
1.5
|
1
|
1
|
2.1
|
| Title | Phase Ib: PK Parameters for AEB071 - AUC0-8hr (Cycle 1; Day 15) |
|---|---|
| Description | Blood samples were collected from all patients during Cycle 1 (Days 1 and 15) for pharmacokinetic profiling. On Days 8 and 22 of Cycle 1, trough samples were collected. Additionally, pre-dose samples were collected on Day 1 of Cycle 2 through Cycle 6. |
| Time Frame | Cycle 1 (Day 15) |
Outcome Measure Data
| Analysis Population Description |
|---|
| This analysis group is comprised of the Pharmacokinetic Analysis Set (PAS), which is all patients who have evaluable pharmacokinetic (PK) data. The PAS will be used for summaries (tables and figures) and listings of PK data. |
| Arm/Group Title | Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (PAS) | Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (PAS) | Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (PAS) | Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (PAS) | Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (PAS) | Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (PAS) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. |
| Measure Participants | 6 | 4 | 2 | 5 | 5 | 5 |
| Geometric Mean (Geometric Coefficient of Variation) [hr*ng/ml] |
5879.9
(32.46)
|
6330.3
(29.28)
|
16737.1
(17.56)
|
15313.6
(105.21)
|
15055.5
(78.89)
|
20629.7
(11.81)
|
| Title | Phase lb: PK Parameters for AEB071 - Cmax (Cycle 1; Day 15) |
|---|---|
| Description | Blood samples were collected from all patients during Cycle 1 (Days 1 and 15) for pharmacokinetic profiling. On Days 8 and 22 of Cycle 1, trough samples were collected. Additionally, pre-dose samples were collected on Day 1 of Cycle 2 through Cycle 6. |
| Time Frame | Cycle 1 (Day 15) |
Outcome Measure Data
| Analysis Population Description |
|---|
| This analysis group is comprised of the Pharmacokinetic Analysis Set (PAS), which is all patients who have evaluable pharmacokinetic (PK) data. The PAS will be used for summaries (tables and figures) and listings of PK data. |
| Arm/Group Title | Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (PAS) | Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (PAS) | Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (PAS) | Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (PAS) | Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (PAS) | Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (PAS) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. |
| Measure Participants | 6 | 4 | 2 | 5 | 5 | 5 |
| Geometric Mean (Geometric Coefficient of Variation) [ng/ml] |
1244.6
(27.5)
|
1347.1
(28.56)
|
3065.6
(60.1)
|
3263.8
(96.11)
|
3597.2
(62.84)
|
3716.5
(23.72)
|
| Title | Phase lb: PK Parameters for AEB071 - Tmax (Cycle 1; Day 15) |
|---|---|
| Description | Blood samples were collected from all patients during Cycle 1 (Days 1 and 15) for pharmacokinetic profiling. On Days 8 and 22 of Cycle 1, trough samples were collected. Additionally, pre-dose samples were collected on Day 1 of Cycle 2 through Cycle 6. |
| Time Frame | Cycle 1 (Day 15) |
Outcome Measure Data
| Analysis Population Description |
|---|
| This analysis group is comprised of the Pharmacokinetic Analysis Set (PAS), which is all patients who have evaluable pharmacokinetic (PK) data. The PAS will be used for summaries (tables and figures) and listings of PK data. |
| Arm/Group Title | Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (PAS) | Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (PAS) | Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (PAS) | Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (PAS) | Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (PAS) | Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (PAS) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. |
| Measure Participants | 6 | 4 | 2 | 5 | 5 | 5 |
| Median (Full Range) [hr] |
2
|
1.5
|
2.6
|
3.9
|
1.9
|
2.1
|
| Title | Phase Ib: PK Parameters for MEK162 - AUC0-8hr (Cycle 1; Day 1) |
|---|---|
| Description | Blood samples were collected from all patients during Cycle 1 (Days 1 and 15) for pharmacokinetic profiling. On Days 8 and 22 of Cycle 1, trough samples were collected. Additionally, pre-dose samples were collected on Day 1 of Cycle 2 through Cycle 6. |
| Time Frame | Cycle 1 (Day 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| This analysis group is comprised of the Pharmacokinetic Analysis Set (PAS), which is all patients who have evaluable pharmacokinetic (PK) data. The PAS will be used for summaries (tables and figures) and listings of PK data. |
| Arm/Group Title | Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (PAS) | Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (PAS) | Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (PAS) | Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (PAS) | Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (PAS) | Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (PAS) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. |
| Measure Participants | 6 | 5 | 6 | 6 | 5 | 8 |
| Geometric Mean (Geometric Coefficient of Variation) [hr*ng/ml] |
1587.7
(55.75)
|
1496.7
(30.02)
|
1088.7
(49.45)
|
1590.5
(43.49)
|
984.4
(72.57)
|
962
(50.15)
|
| Title | Phase lb: PK Parameters for MEK162 - Cmax (Cycle 1; Day 1) |
|---|---|
| Description | Blood samples were collected from all patients during Cycle 1 (Days 1 and 15) for pharmacokinetic profiling. On Days 8 and 22 of Cycle 1, trough samples were collected. Additionally, pre-dose samples were collected on Day 1 of Cycle 2 through Cycle 6. |
| Time Frame | Cycle 1 (Day 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| This analysis group is comprised of the Pharmacokinetic Analysis Set (PAS), which is all patients who have evaluable pharmacokinetic (PK) data. The PAS will be used for summaries (tables and figures) and listings of PK data. |
| Arm/Group Title | Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (PAS) | Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (PAS) | Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (PAS) | Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (PAS) | Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (PAS) | Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (PAS) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. |
| Measure Participants | 6 | 5 | 6 | 6 | 5 | 8 |
| Geometric Mean (Geometric Coefficient of Variation) [ng/ml] |
362
(46.74)
|
432.6
(56.3)
|
245.4
(63.08)
|
328.4
(59.07)
|
243.5
(53.27)
|
222.8
(58.13)
|
| Title | Phase lb: PK Parameters for MEK162 - Tmax (Cycle 1; Day 1) |
|---|---|
| Description | Blood samples were collected from all patients during Cycle 1 (Days 1 and 15) for pharmacokinetic profiling. On Days 8 and 22 of Cycle 1, trough samples were collected. Additionally, pre-dose samples were collected on Day 1 of Cycle 2 through Cycle 6. |
| Time Frame | Cycle 1 (Day 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| This analysis group is comprised of the Pharmacokinetic Analysis Set (PAS), which is all patients who have evaluable pharmacokinetic (PK) data. The PAS will be used for summaries (tables and figures) and listings of PK data. |
| Arm/Group Title | Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (PAS) | Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (PAS) | Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (PAS) | Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (PAS) | Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (PAS) | Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (PAS) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. |
| Measure Participants | 6 | 5 | 6 | 6 | 5 | 8 |
| Median (Full Range) [hr] |
1.1
|
1.1
|
2
|
4
|
2
|
1.1
|
| Title | Phase Ib: PK Parameters for MEK162 - AUC0-8hr (Cycle 1; Day 15) |
|---|---|
| Description | Blood samples were collected from all patients during Cycle 1 (Days 1 and 15) for pharmacokinetic profiling. On Days 8 and 22 of Cycle 1, trough samples were collected. Additionally, pre-dose samples were collected on Day 1 of Cycle 2 through Cycle 6. |
| Time Frame | Cycle 1 (Day 15) |
Outcome Measure Data
| Analysis Population Description |
|---|
| This analysis group is comprised of the Pharmacokinetic Analysis Set (PAS), which is all patients who have evaluable pharmacokinetic (PK) data. The PAS will be used for summaries (tables and figures) and listings of PK data. |
| Arm/Group Title | Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (PAS) | Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (PAS) | Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (PAS) | Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (PAS) | Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (PAS) | Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (PAS) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. |
| Measure Participants | 6 | 4 | 4 | 4 | 5 | 4 |
| Geometric Mean (Geometric Coefficient of Variation) [hr*ng/ml] |
1807.4
(43.6)
|
1927.9
(42.48)
|
1374.2
(68.21)
|
1454.7
(41.13)
|
1268.5
(70.41)
|
1275.8
(39.04)
|
| Title | Phase lb: PK Parameters for MEK162 - Cmax (Cycle 1; Day 15) |
|---|---|
| Description | Blood samples were collected from all patients during Cycle 1 (Days 1 and 15) for pharmacokinetic profiling. On Days 8 and 22 of Cycle 1, trough samples were collected. Additionally, pre-dose samples were collected on Day 1 of Cycle 2 through Cycle 6. |
| Time Frame | Cycle 1 (Day 15) |
Outcome Measure Data
| Analysis Population Description |
|---|
| This analysis group is comprised of the Pharmacokinetic Analysis Set (PAS), which is all patients who have evaluable pharmacokinetic (PK) data. The PAS will be used for summaries (tables and figures) and listings of PK data. |
| Arm/Group Title | Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (PAS) | Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (PAS) | Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (PAS) | Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (PAS) | Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (PAS) | Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (PAS) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. |
| Measure Participants | 6 | 4 | 4 | 4 | 5 | 4 |
| Geometric Mean (Geometric Coefficient of Variation) [ng/ml] |
454.5
(42.42)
|
418.9
(34.62)
|
307
(88.45)
|
362.7
(59.8)
|
340.7
(80.64)
|
284.1
(52.79)
|
| Title | Phase lb: PK Parameters for MEK162 - Tmax (Cycle 1; Day 15) |
|---|---|
| Description | Blood samples were collected from all patients during Cycle 1 (Days 1 and 15) for pharmacokinetic profiling. On Days 8 and 22 of Cycle 1, trough samples were collected. Additionally, pre-dose samples were collected on Day 1 of Cycle 2 through Cycle 6. |
| Time Frame | Cycle 1 (Day 15) |
Outcome Measure Data
| Analysis Population Description |
|---|
| This analysis group is comprised of the Pharmacokinetic Analysis Set (PAS), which is all patients who have evaluable pharmacokinetic (PK) data. The PAS will be used for summaries (tables and figures) and listings of PK data. |
| Arm/Group Title | Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (PAS) | Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (PAS) | Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (PAS) | Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (PAS) | Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (PAS) | Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (PAS) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. |
| Measure Participants | 6 | 4 | 4 | 4 | 5 | 4 |
| Median (Full Range) [hr] |
2
|
1.6
|
3
|
2.9
|
1.9
|
1.5
|
Adverse Events
| Time Frame | Adverse Events (AEs) were collected for approximately 2 years (August, 2013 through May, 2015), which was the duration of the trial. | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | AE reporting is comprised of the Safety Set (SS), which is all patients who received at least one dose of AEB071 and MEK162, and have at least one valid post-baseline safety assessment. | |||||||||||
| Arm/Group Title | Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (SS) | Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (SS) | Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (SS) | Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (SS) | Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (SS) | Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (SS) | ||||||
| Arm/Group Description | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | ||||||
All Cause Mortality |
||||||||||||
| Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (SS) | Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (SS) | Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (SS) | Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (SS) | Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (SS) | Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (SS) | |||||||
| 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 | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||||
Serious Adverse Events |
||||||||||||
| Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (SS) | Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (SS) | Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (SS) | Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (SS) | Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (SS) | Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (SS) | |||||||
| 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 | 3/6 (50%) | 1/6 (16.7%) | 3/6 (50%) | 4/6 (66.7%) | 2/6 (33.3%) | 6/8 (75%) | ||||||
| Blood and lymphatic system disorders | ||||||||||||
| ANAEMIA | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/8 (0%) | 0 |
| Cardiac disorders | ||||||||||||
| SINUS TACHYCARDIA | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 |
| Endocrine disorders | ||||||||||||
| HYPOTHYROIDISM | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||
| ABDOMINAL PAIN | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/8 (0%) | 0 |
| ASCITES | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/8 (0%) | 0 |
| DIARRHOEA | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 | 0/8 (0%) | 0 |
| GASTROINTESTINAL HAEMORRHAGE | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 |
| NAUSEA | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 | 4/8 (50%) | 4 |
| OESOPHAGEAL VARICES HAEMORRHAGE | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/8 (0%) | 0 |
| VOMITING | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 3/6 (50%) | 3 | 1/6 (16.7%) | 1 | 2/8 (25%) | 2 |
| General disorders | ||||||||||||
| FATIGUE | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/8 (0%) | 0 |
| GENERAL PHYSICAL HEALTH DETERIORATION | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 |
| MALAISE | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/8 (0%) | 0 |
| OEDEMA PERIPHERAL | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/8 (0%) | 0 |
| PYREXIA | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/8 (25%) | 2 |
| Hepatobiliary disorders | ||||||||||||
| ACUTE HEPATIC FAILURE | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 |
| HEPATIC FAILURE | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 |
| HEPATOMEGALY | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 |
| Infections and infestations | ||||||||||||
| ESCHERICHIA BACTERAEMIA | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 |
| INFECTION | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 |
| URINARY TRACT INFECTION | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 |
| Investigations | ||||||||||||
| BLOOD CREATININE INCREASED | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||||
| DEHYDRATION | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 |
| HYPOCALCAEMIA | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 |
| Renal and urinary disorders | ||||||||||||
| ACUTE KIDNEY INJURY | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||
| DYSPNOEA | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/8 (0%) | 0 |
| PNEUMOTHORAX | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 |
| PULMONARY EMBOLISM | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||||||||
| Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (SS) | Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (SS) | Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (SS) | Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (SS) | Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (SS) | Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (SS) | |||||||
| 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 | 6/6 (100%) | 6/6 (100%) | 6/6 (100%) | 6/6 (100%) | 6/6 (100%) | 8/8 (100%) | ||||||
| Blood and lymphatic system disorders | ||||||||||||
| ANAEMIA | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 3/6 (50%) | 3 | 3/6 (50%) | 3 | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 |
| THROMBOCYTOPENIA | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/6 (33.3%) | 2 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/8 (0%) | 0 |
| Eye disorders | ||||||||||||
| CHORIORETINOPATHY | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 5/8 (62.5%) | 5 |
| RETINAL DETACHMENT | 2/6 (33.3%) | 2 | 3/6 (50%) | 3 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/8 (0%) | 0 |
| VISION BLURRED | 0/6 (0%) | 0 | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 | 2/6 (33.3%) | 2 | 1/6 (16.7%) | 1 | 2/8 (25%) | 2 |
| VISUAL IMPAIRMENT | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 3/8 (37.5%) | 3 |
| CATARACT | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 |
| EYE DISORDER | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 |
| EYELID OEDEMA | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 |
| MACULAR OEDEMA | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 |
| PERIORBITAL OEDEMA | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 |
| RETINAL OEDEMA | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 |
| RETINOPATHY | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/8 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||
| DIARRHOEA | 6/6 (100%) | 6 | 5/6 (83.3%) | 5 | 6/6 (100%) | 6 | 6/6 (100%) | 6 | 6/6 (100%) | 6 | 8/8 (100%) | 8 |
| NAUSEA | 6/6 (100%) | 6 | 3/6 (50%) | 3 | 4/6 (66.7%) | 4 | 6/6 (100%) | 6 | 4/6 (66.7%) | 4 | 7/8 (87.5%) | 7 |
| VOMITING | 5/6 (83.3%) | 5 | 3/6 (50%) | 3 | 5/6 (83.3%) | 5 | 5/6 (83.3%) | 5 | 5/6 (83.3%) | 5 | 7/8 (87.5%) | 7 |
| CONSTIPATION | 2/6 (33.3%) | 2 | 2/6 (33.3%) | 2 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 4/8 (50%) | 4 |
| ABDOMINAL PAIN | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 2 | 3/6 (50%) | 3 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 |
| STOMATITIS | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 | 2/6 (33.3%) | 2 | 0/8 (0%) | 0 |
| DYSPEPSIA | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 2/8 (25%) | 2 |
| FLATULENCE | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 1/8 (12.5%) | 1 |
| DRY MOUTH | 0/6 (0%) | 0 | 2/6 (33.3%) | 2 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 |
| GASTROOESOPHAGEAL REFLUX DISEASE | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/8 (0%) | 0 |
| ABDOMINAL PAIN UPPER | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/6 (33.3%) | 2 | 0/8 (0%) | 0 |
| GASTRITIS | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 |
| IMPAIRED GASTRIC EMPTYING | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 |
| General disorders | ||||||||||||
| FATIGUE | 3/6 (50%) | 3 | 4/6 (66.7%) | 4 | 3/6 (50%) | 3 | 3/6 (50%) | 3 | 3/6 (50%) | 3 | 5/8 (62.5%) | 5 |
| OEDEMA PERIPHERAL | 2/6 (33.3%) | 2 | 2/6 (33.3%) | 2 | 4/6 (66.7%) | 4 | 3/6 (50%) | 3 | 2/6 (33.3%) | 2 | 3/8 (37.5%) | 3 |
| ASTHENIA | 3/6 (50%) | 3 | 2/6 (33.3%) | 2 | 2/6 (33.3%) | 2 | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 | 3/8 (37.5%) | 3 |
| PYREXIA | 2/6 (33.3%) | 2 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 |
| MALAISE | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 |
| CHILLS | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/8 (25%) | 2 |
| Hepatobiliary disorders | ||||||||||||
| HEPATIC PAIN | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 |
| Infections and infestations | ||||||||||||
| RASH PUSTULAR | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 4/6 (66.7%) | 4 | 2/8 (25%) | 2 |
| Investigations | ||||||||||||
| BLOOD CREATINE PHOSPHOKINASE INCREASED | 4/6 (66.7%) | 4 | 5/6 (83.3%) | 5 | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 2 | 3/6 (50%) | 3 | 2/8 (25%) | 2 |
| ASPARTATE AMINOTRANSFERASE INCREASED | 1/6 (16.7%) | 1 | 4/6 (66.7%) | 4 | 1/6 (16.7%) | 1 | 3/6 (50%) | 3 | 3/6 (50%) | 3 | 0/8 (0%) | 0 |
| WEIGHT DECREASED | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/6 (33.3%) | 2 | 3/6 (50%) | 3 | 1/6 (16.7%) | 1 | 2/8 (25%) | 2 |
| ALANINE AMINOTRANSFERASE INCREASED | 2/6 (33.3%) | 2 | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/8 (0%) | 0 |
| EJECTION FRACTION DECREASED | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 2 | 2/8 (25%) | 2 |
| LYMPHOCYTE COUNT DECREASED | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/8 (0%) | 0 |
| BLOOD CREATININE INCREASED | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 3/6 (50%) | 3 | 0/6 (0%) | 0 | 0/8 (0%) | 0 |
| BLOOD LACTATE DEHYDROGENASE INCREASED | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 |
| WEIGHT INCREASED | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 |
| Metabolism and nutrition disorders | ||||||||||||
| DECREASED APPETITE | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 2 | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 2 | 1/6 (16.7%) | 1 | 3/8 (37.5%) | 3 |
| DEHYDRATION | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 2 | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 |
| HYPERKALAEMIA | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 |
| HYPOALBUMINAEMIA | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 |
| HYPOKALAEMIA | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 2 | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 |
| CACHEXIA | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||||||||||
| MYALGIA | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 1/8 (12.5%) | 1 |
| BACK PAIN | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/8 (0%) | 0 |
| MUSCLE SPASMS | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||
| TUMOUR PAIN | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/8 (0%) | 0 |
| Nervous system disorders | ||||||||||||
| DYSGEUSIA | 2/6 (33.3%) | 2 | 2/6 (33.3%) | 2 | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 2 | 2/6 (33.3%) | 2 | 0/8 (0%) | 0 |
| CEREBROVASCULAR DISORDER | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/8 (25%) | 2 |
| NEUROPATHY PERIPHERAL | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/8 (0%) | 0 |
| PRESYNCOPE | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 |
| Psychiatric disorders | ||||||||||||
| ANXIETY | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 |
| Renal and urinary disorders | ||||||||||||
| CHROMATURIA | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 |
| RENAL COLIC | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/8 (25%) | 2 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||
| DYSPNOEA | 3/6 (50%) | 3 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 |
| COUGH | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 2 | 0/8 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||||
| RASH | 5/6 (83.3%) | 5 | 2/6 (33.3%) | 2 | 2/6 (33.3%) | 2 | 3/6 (50%) | 3 | 2/6 (33.3%) | 2 | 1/8 (12.5%) | 1 |
| DERMATITIS ACNEIFORM | 0/6 (0%) | 0 | 3/6 (50%) | 3 | 3/6 (50%) | 3 | 3/6 (50%) | 3 | 2/6 (33.3%) | 2 | 0/8 (0%) | 0 |
| PRURITUS | 2/6 (33.3%) | 2 | 2/6 (33.3%) | 2 | 2/6 (33.3%) | 2 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 |
| DRY SKIN | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 2 | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 | 0/8 (0%) | 0 |
| ACNE | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/8 (25%) | 2 |
| RASH MACULO-PAPULAR | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 |
| ALOPECIA | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 |
| PAIN OF SKIN | 2/6 (33.3%) | 2 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 |
| ERYTHEMA | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/8 (0%) | 0 |
| HYPERHIDROSIS | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 |
| RASH FOLLICULAR | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/8 (0%) | 0 |
| XERODERMA | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/8 (0%) | 0 |
| Vascular disorders | ||||||||||||
| HYPERTENSION | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 3/8 (37.5%) | 3 |
Limitations/Caveats
Due to an enrollment halt, the Phase II part of the study was not conducted. The sponsor decided to permanently stop recruitment for the study prior to MTD determination.
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 |
| clinicaltrials@arraybiopharma.com |
Responsible Party:
Array Biopharma, now a wholly owned subsidiary of Pfizer
ClinicalTrials.gov Identifier:
NCT01801358
Other Study ID Numbers:
- CMEK162X2203
First Posted:
Feb 28, 2013
Last Update Posted:
Sep 16, 2020
Last Verified:
Sep 1, 2020