Not provided
Not provided
Not provided
Not provided
Not provided
The trial was terminated for scientific reasons.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A | Experimental | AEB071 and MEK162 combined |
|
| Arm B | Experimental | MEK162 alone |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AEB071 | Drug | Twice-daily doses of AEB071 for a cycle of 28-days, given without interruption (continuous cycles) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | 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. | Cycle 1 (up to 28 days) |
| Phase II: Progression Free Survival (PFS) | 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. | From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit) |
| Measure | Description | Time Frame |
|---|---|---|
| Phase Ib/II: The Number of Subjects Experiencing At Least One Adverse Event (AE) | 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. | From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit) |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Dana Farber Cancer Institute Dept. Onc | Boston | Massachusetts | 02215 | United States | ||
| Memorial Sloan Kettering Cancer Center Dept of Onc.. |
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.
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.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (FAS) | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. |
| FG001 | Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (FAS) | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. |
| FG002 | Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (FAS) | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. |
| FG003 | Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (FAS) | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. |
| FG004 | Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (FAS) | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. |
| FG005 | Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (FAS) | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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 provided
| ID | Title | Description |
|---|---|---|
| BG000 | Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (FAS) | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. |
| BG001 | Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (FAS) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | 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. | 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. | Posted | Number | DLTs | Cycle 1 (up to 28 days) |
|
Adverse Events (AEs) were collected for approximately 2 years (August, 2013 through May, 2015), which was the duration of the trial.
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.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (SS) | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| BLOOD CREATININE INCREASED | Investigations | MedDRA (18.0) | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| HYPERTENSION | Vascular disorders | MedDRA (18.0) | Non-systematic Assessment |
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Array BioPharma, Inc. | 303-381-6604 | clinicaltrials@arraybiopharma.com |
| ID | Term |
|---|---|
| D000098943 | Uveal Melanoma |
| D008545 | Melanoma |
| ID | Term |
|---|---|
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
Not provided
Not provided
| ID | Term |
|---|---|
| C543528 | sotrastaurin |
| C581313 | binimetinib |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| MEK162 | Drug | Twice-daily doses of MEK162 for a cycle of 28-days, given without interruption (continuous cycles) |
|
| Phase Ib/II: The Number of Subjects Experiencing At Least One Serious Adverse Event (SAE) | Serious adverse event (SAE) is defined as one of the following:
| From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit) |
| Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Best Overall Response (BOR) | 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. | Cycle 1 (up to 28 days) |
| Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Duration of Response (DOR) | 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. | Cycle 1 (up to 28 days) |
| Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Progression Free Survival (PFS) | 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. | Cycle 1 (up to 28 days) |
| Phase II: Evaluation of Preliminary Anti-tumor Activity - Overall Response Rate (CR+PR) | 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. | From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit) |
| Phase II: Evaluation of Preliminary Anti-tumor Activity - Best Overall Response (BOR) | 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. | From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit) |
| Phase II: Evaluation of Preliminary Anti-tumor Activity - Duration of Response (DOR) | 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. | From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit) |
| Phase II: Evaluation of Preliminary Anti-tumor Activity - Overall Survival (OS) | 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. | From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit) |
| Phase Ib: PK Parameters for AEB071 - AUC0-8hr (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. | Cycle 1 (Day 1) |
| Phase lb: PK Parameters for AEB071 - Cmax (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. | Cycle 1 (Day 1) |
| Phase lb: PK Parameters for AEB071 - Tmax (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. | Cycle 1 (Day 1) |
| Phase Ib: PK Parameters for AEB071 - AUC0-8hr (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. | Cycle 1 (Day 15) |
| Phase lb: PK Parameters for AEB071 - Cmax (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. | Cycle 1 (Day 15) |
| Phase lb: PK Parameters for AEB071 - Tmax (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. | Cycle 1 (Day 15) |
| Phase Ib: PK Parameters for MEK162 - AUC0-8hr (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. | Cycle 1 (Day 1) |
| Phase lb: PK Parameters for MEK162 - Cmax (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. | Cycle 1 (Day 1) |
| Phase lb: PK Parameters for MEK162 - Tmax (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. | Cycle 1 (Day 1) |
| Phase Ib: PK Parameters for MEK162 - AUC0-8hr (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. | Cycle 1 (Day 15) |
| Phase lb: PK Parameters for MEK162 - Cmax (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. | Cycle 1 (Day 15) |
| Phase lb: PK Parameters for MEK162 - Tmax (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. | Cycle 1 (Day 15) |
| New York |
| New York |
| 90033 |
| United States |
| Pfizer Investigative Site | Paris | 75231 | France |
| Pfizer Investigative Site | Essen | 45147 | Germany |
| Pfizer Investigative Site | Leiden | 2300 RC | Netherlands |
| Pfizer Investigative Site | Madrid | 28050 | Spain |
| Pfizer Investigative Site | London | SW3 6JJ | United Kingdom |
| Physician Decision |
|
| Progressive Disease |
|
| Withdrawal by Subject |
|
Phase Ib (Dose Escalation)
Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid.
| BG002 | Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (FAS) | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. |
| BG003 | Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (FAS) | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. |
| BG004 | Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (FAS) | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. |
| BG005 | Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (FAS) | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. |
| BG006 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Region of Enrollment | Number | participants |
|
| Baseline WHO Performance Status | Categories:
| Number | participants |
|
| OG001 | Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. |
| OG002 | Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. |
| OG003 | Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. |
| OG004 | Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. |
| OG005 | Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. |
|
|
| Primary | Phase II: Progression Free Survival (PFS) | 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. | Posted | From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit) |
|
|
| Secondary | Phase Ib/II: The Number of Subjects Experiencing At Least One Adverse Event (AE) | 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. | 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. | Posted | Number | participants | From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit) |
|
|
|
| Secondary | Phase Ib/II: The Number of Subjects Experiencing At Least One Serious Adverse Event (SAE) | Serious adverse event (SAE) is defined as one of the following:
| 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. | Posted | Number | participants | From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit) |
|
|
|
| Secondary | Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Best Overall Response (BOR) | 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. | 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. | Posted | Number | participants | Cycle 1 (up to 28 days) |
|
|
|
| Secondary | Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Duration of Response (DOR) | 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. | 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. | Posted | Cycle 1 (up to 28 days) |
|
|
| Secondary | Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Progression Free Survival (PFS) | 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. | 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. | Posted | Median | Inter-Quartile Range | weeks | Cycle 1 (up to 28 days) |
|
|
|
| Secondary | Phase II: Evaluation of Preliminary Anti-tumor Activity - Overall Response Rate (CR+PR) | 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. | 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. | Posted | From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit) |
|
|
| Secondary | Phase II: Evaluation of Preliminary Anti-tumor Activity - Best Overall Response (BOR) | 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. | 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. | Posted | From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit) |
|
|
| Secondary | Phase II: Evaluation of Preliminary Anti-tumor Activity - Duration of Response (DOR) | 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. | 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. | Posted | From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit) |
|
|
| Secondary | Phase II: Evaluation of Preliminary Anti-tumor Activity - Overall Survival (OS) | 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. | 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. | Posted | From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit) |
|
|
| Secondary | Phase Ib: PK Parameters for AEB071 - AUC0-8hr (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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | hr*ng/ml | Cycle 1 (Day 1) |
|
|
|
| Secondary | Phase lb: PK Parameters for AEB071 - Cmax (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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/ml | Cycle 1 (Day 1) |
|
|
|
| Secondary | Phase lb: PK Parameters for AEB071 - Tmax (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. | 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. | Posted | Median | Full Range | hr | Cycle 1 (Day 1) |
|
|
|
| Secondary | Phase Ib: PK Parameters for AEB071 - AUC0-8hr (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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | hr*ng/ml | Cycle 1 (Day 15) |
|
|
|
| Secondary | Phase lb: PK Parameters for AEB071 - Cmax (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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/ml | Cycle 1 (Day 15) |
|
|
|
| Secondary | Phase lb: PK Parameters for AEB071 - Tmax (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. | 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. | Posted | Median | Full Range | hr | Cycle 1 (Day 15) |
|
|
|
| Secondary | Phase Ib: PK Parameters for MEK162 - AUC0-8hr (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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | hr*ng/ml | Cycle 1 (Day 1) |
|
|
|
| Secondary | Phase lb: PK Parameters for MEK162 - Cmax (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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/ml | Cycle 1 (Day 1) |
|
|
|
| Secondary | Phase lb: PK Parameters for MEK162 - Tmax (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. | 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. | Posted | Median | Full Range | hr | Cycle 1 (Day 1) |
|
|
|
| Secondary | Phase Ib: PK Parameters for MEK162 - AUC0-8hr (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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | hr*ng/ml | Cycle 1 (Day 15) |
|
|
|
| Secondary | Phase lb: PK Parameters for MEK162 - Cmax (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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/ml | Cycle 1 (Day 15) |
|
|
|
| Secondary | Phase lb: PK Parameters for MEK162 - Tmax (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. | 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. | Posted | Median | Full Range | hr | Cycle 1 (Day 15) |
|
|
|
| 3 |
| 6 |
| 6 |
| 6 |
| EG001 | Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (SS) | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | 1 | 6 | 6 | 6 |
| EG002 | Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (SS) | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | 3 | 6 | 6 | 6 |
| EG003 | Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (SS) | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | 4 | 6 | 6 | 6 |
| EG004 | Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (SS) | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | 2 | 6 | 6 | 6 |
| EG005 | Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (SS) | Phase Ib (Dose Escalation) Phase Ib was the combination of sotrastaurin and binimetinib administered orally bid. | 6 | 8 | 8 | 8 |
| SINUS TACHYCARDIA | Cardiac disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| DYSPNOEA | Respiratory, thoracic and mediastinal disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| PNEUMOTHORAX | Respiratory, thoracic and mediastinal disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| PULMONARY EMBOLISM | Respiratory, thoracic and mediastinal disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| ANAEMIA | Blood and lymphatic system disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| FATIGUE | General disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| GENERAL PHYSICAL HEALTH DETERIORATION | General disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| MALAISE | General disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| OEDEMA PERIPHERAL | General disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| PYREXIA | General disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| ABDOMINAL PAIN | Gastrointestinal disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| ASCITES | Gastrointestinal disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| DIARRHOEA | Gastrointestinal disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| GASTROINTESTINAL HAEMORRHAGE | Gastrointestinal disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| NAUSEA | Gastrointestinal disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| OESOPHAGEAL VARICES HAEMORRHAGE | Gastrointestinal disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| VOMITING | Gastrointestinal disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| ACUTE KIDNEY INJURY | Renal and urinary disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| ACUTE HEPATIC FAILURE | Hepatobiliary disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| HEPATIC FAILURE | Hepatobiliary disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| HEPATOMEGALY | Hepatobiliary disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| HYPOTHYROIDISM | Endocrine disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| DEHYDRATION | Metabolism and nutrition disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| HYPOCALCAEMIA | Metabolism and nutrition disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| ESCHERICHIA BACTERAEMIA | Infections and infestations | MedDRA (18.0) | Non-systematic Assessment |
|
| INFECTION | Infections and infestations | MedDRA (18.0) | Non-systematic Assessment |
|
| URINARY TRACT INFECTION | Infections and infestations | MedDRA (18.0) | Non-systematic Assessment |
|
| TUMOUR PAIN | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (18.0) | Non-systematic Assessment |
|
| FATIGUE | General disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| OEDEMA PERIPHERAL | General disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| ASTHENIA | General disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| PYREXIA | General disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| MALAISE | General disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| CHILLS | General disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| ANXIETY | Psychiatric disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| BLOOD CREATINE PHOSPHOKINASE INCREASED | Investigations | MedDRA (18.0) | Non-systematic Assessment |
|
| ASPARTATE AMINOTRANSFERASE INCREASED | Investigations | MedDRA (18.0) | Non-systematic Assessment |
|
| WEIGHT DECREASED | Investigations | MedDRA (18.0) | Non-systematic Assessment |
|
| ALANINE AMINOTRANSFERASE INCREASED | Investigations | MedDRA (18.0) | Non-systematic Assessment |
|
| EJECTION FRACTION DECREASED | Investigations | MedDRA (18.0) | Non-systematic Assessment |
|
| LYMPHOCYTE COUNT DECREASED | Investigations | MedDRA (18.0) | Non-systematic Assessment |
|
| BLOOD CREATININE INCREASED | Investigations | MedDRA (18.0) | Non-systematic Assessment |
|
| BLOOD LACTATE DEHYDROGENASE INCREASED | Investigations | MedDRA (18.0) | Non-systematic Assessment |
|
| WEIGHT INCREASED | Investigations | MedDRA (18.0) | Non-systematic Assessment |
|
| DYSPNOEA | Respiratory, thoracic and mediastinal disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| COUGH | Respiratory, thoracic and mediastinal disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| ANAEMIA | Blood and lymphatic system disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| THROMBOCYTOPENIA | Blood and lymphatic system disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| DYSGEUSIA | Nervous system disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| CEREBROVASCULAR DISORDER | Nervous system disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| NEUROPATHY PERIPHERAL | Nervous system disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| PRESYNCOPE | Nervous system disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| CHORIORETINOPATHY | Eye disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| RETINAL DETACHMENT | Eye disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| VISION BLURRED | Eye disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| VISUAL IMPAIRMENT | Eye disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| CATARACT | Eye disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| EYE DISORDER | Eye disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| EYELID OEDEMA | Eye disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| MACULAR OEDEMA | Eye disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| PERIORBITAL OEDEMA | Eye disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| RETINAL OEDEMA | Eye disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| RETINOPATHY | Eye disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| DIARRHOEA | Gastrointestinal disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| NAUSEA | Gastrointestinal disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| VOMITING | Gastrointestinal disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| CONSTIPATION | Gastrointestinal disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| ABDOMINAL PAIN | Gastrointestinal disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| STOMATITIS | Gastrointestinal disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| DYSPEPSIA | Gastrointestinal disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| FLATULENCE | Gastrointestinal disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| DRY MOUTH | Gastrointestinal disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| GASTROOESOPHAGEAL REFLUX DISEASE | Gastrointestinal disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| ABDOMINAL PAIN UPPER | Gastrointestinal disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| GASTRITIS | Gastrointestinal disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| IMPAIRED GASTRIC EMPTYING | Gastrointestinal disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| HEPATIC PAIN | Hepatobiliary disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| CHROMATURIA | Renal and urinary disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| RENAL COLIC | Renal and urinary disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| RASH | Skin and subcutaneous tissue disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| DERMATITIS ACNEIFORM | Skin and subcutaneous tissue disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| PRURITUS | Skin and subcutaneous tissue disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| DRY SKIN | Skin and subcutaneous tissue disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| ACNE | Skin and subcutaneous tissue disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| RASH MACULO-PAPULAR | Skin and subcutaneous tissue disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| ALOPECIA | Skin and subcutaneous tissue disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| PAIN OF SKIN | Skin and subcutaneous tissue disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| ERYTHEMA | Skin and subcutaneous tissue disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| HYPERHIDROSIS | Skin and subcutaneous tissue disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| RASH FOLLICULAR | Skin and subcutaneous tissue disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| XERODERMA | Skin and subcutaneous tissue disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| MYALGIA | Musculoskeletal and connective tissue disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| BACK PAIN | Musculoskeletal and connective tissue disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| MUSCLE SPASMS | Musculoskeletal and connective tissue disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| DECREASED APPETITE | Metabolism and nutrition disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| DEHYDRATION | Metabolism and nutrition disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| HYPERKALAEMIA | Metabolism and nutrition disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| HYPOALBUMINAEMIA | Metabolism and nutrition disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| HYPOKALAEMIA | Metabolism and nutrition disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| CACHEXIA | Metabolism and nutrition disorders | MedDRA (18.0) | Non-systematic Assessment |
|
| RASH PUSTULAR | Infections and infestations | MedDRA (18.0) | Non-systematic Assessment |
|
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.
| D009369 | Neoplasms |
| D009380 | Neoplasms, Nerve Tissue |
| D018326 | Nevi and Melanomas |
| D014604 | Uveal Neoplasms |
| D005134 | Eye Neoplasms |
| D009371 | Neoplasms by Site |
| D005128 | Eye Diseases |
| D014603 | Uveal Diseases |
| D012878 | Skin Neoplasms |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| Partial Response |
|
| Stable Disease |
|
| Progressive disease |
|
| Unknown |
|