Uveal Melanoma
Conditions
Keywords
Melanoma,, melanoma of the eye,, uveal,, MEK162,, AEB071
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
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.
Interventions
DRUGAEB071
Twice-daily doses of AEB071 for a cycle of 28-days, given without interruption (continuous cycles)
DRUGMEK162
Twice-daily doses of MEK162 for a cycle of 28-days, given without interruption (continuous cycles)
Sponsors
Array Biopharma, now a wholly owned subsidiary of Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
France, Germany, Netherlands, Spain, United Kingdom, United States
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 6 |
| 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. | 6 |
| 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. | 6 |
| 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. | 6 |
| 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. | 6 |
| 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. | 8 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 | 1 | 0 | 0 | 1 |
| Overall Study | Physician Decision | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Progressive Disease | 6 | 4 | 4 | 5 | 6 | 5 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 | 2 |
Baseline characteristics
| Characteristic | 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 150 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 |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 3 Participants | 1 Participants | 2 Participants | 3 Participants | 11 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 5 Participants | 3 Participants | 5 Participants | 4 Participants | 5 Participants | 27 Participants |
| Age, Continuous | 57.0 years STANDARD_DEVIATION 10.43 | 52.8 years STANDARD_DEVIATION 10.82 | 59.8 years STANDARD_DEVIATION 9.11 | 48.7 years STANDARD_DEVIATION 15.21 | 56.8 years STANDARD_DEVIATION 10.87 | 61.5 years STANDARD_DEVIATION 10.65 | 56.4 years STANDARD_DEVIATION 11.39 |
| Baseline WHO Performance Status 0: | 6 participants | 5 participants | 5 participants | 3 participants | 5 participants | 8 participants | 32 participants |
| Baseline WHO Performance Status 1: | 0 participants | 1 participants | 1 participants | 3 participants | 1 participants | 0 participants | 6 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 1 participants | 2 participants | 1 participants | 1 participants | 1 participants | 0 participants | 6 participants |
| Race/Ethnicity, Customized Other | 1 participants | 2 participants | 4 participants | 2 participants | 4 participants | 8 participants | 21 participants |
| Race/Ethnicity, Customized Russian | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Unknown | 4 participants | 2 participants | 1 participants | 2 participants | 1 participants | 0 participants | 10 participants |
| Region of Enrollment France | 3 participants | 1 participants | 1 participants | 2 participants | 0 participants | 0 participants | 7 participants |
| Region of Enrollment Germany | 1 participants | 0 participants | 1 participants | 2 participants | 1 participants | 6 participants | 11 participants |
| Region of Enrollment Netherlands | 0 participants | 1 participants | 1 participants | 0 participants | 1 participants | 2 participants | 5 participants |
| Region of Enrollment Spain | 1 participants | 2 participants | 1 participants | 1 participants | 1 participants | 0 participants | 6 participants |
| Region of Enrollment United Kingdom | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants | 2 participants |
| Region of Enrollment United States | 0 participants | 2 participants | 2 participants | 1 participants | 2 participants | 0 participants | 7 participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 2 Participants | 3 Participants | 2 Participants | 2 Participants | 14 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 4 Participants | 3 Participants | 4 Participants | 6 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 6 | 6 / 6 | 6 / 6 | 6 / 6 | 6 / 6 | 8 / 8 |
| serious Total, serious adverse events | 3 / 6 | 1 / 6 | 3 / 6 | 4 / 6 | 2 / 6 | 6 / 8 |
Outcome results
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.
Time frame: Cycle 1 (up to 28 days)
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Malaise | 0 DLTs |
| Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Fatigue | 0 DLTs |
| Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Rash | 0 DLTs |
| Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Ejection Fraction Decreased | 0 DLTs |
| Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | General Physical Health Deterioration | 0 DLTs |
| Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Diarrhoea | 0 DLTs |
| Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Anaemia | 0 DLTs |
| Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Vomiting | 0 DLTs |
| Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Nausea | 0 DLTs |
| Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Blood Creatinine Increased | 0 DLTs |
| Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Dermatitis Acneiform | 0 DLTs |
| Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Dermatitis Acneiform | 2 DLTs |
| Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Malaise | 0 DLTs |
| Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Nausea | 0 DLTs |
| Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Fatigue | 0 DLTs |
| Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Vomiting | 0 DLTs |
| Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Rash | 0 DLTs |
| Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Ejection Fraction Decreased | 0 DLTs |
| Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Blood Creatinine Increased | 0 DLTs |
| Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Anaemia | 0 DLTs |
| Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | General Physical Health Deterioration | 0 DLTs |
| Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Diarrhoea | 0 DLTs |
| Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | General Physical Health Deterioration | 1 DLTs |
| Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Blood Creatinine Increased | 0 DLTs |
| Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Malaise | 0 DLTs |
| Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Diarrhoea | 2 DLTs |
| Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Anaemia | 0 DLTs |
| Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Vomiting | 0 DLTs |
| Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Dermatitis Acneiform | 0 DLTs |
| Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Nausea | 0 DLTs |
| Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Rash | 0 DLTs |
| Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Ejection Fraction Decreased | 0 DLTs |
| Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Fatigue | 1 DLTs |
| Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Dermatitis Acneiform | 0 DLTs |
| Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Anaemia | 1 DLTs |
| Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Diarrhoea | 1 DLTs |
| Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Vomiting | 1 DLTs |
| Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Nausea | 1 DLTs |
| Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Fatigue | 1 DLTs |
| Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | General Physical Health Deterioration | 0 DLTs |
| Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Malaise | 1 DLTs |
| Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Blood Creatinine Increased | 0 DLTs |
| Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Ejection Fraction Decreased | 0 DLTs |
| Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Rash | 1 DLTs |
| Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Blood Creatinine Increased | 1 DLTs |
| Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Vomiting | 1 DLTs |
| Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Rash | 0 DLTs |
| Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Dermatitis Acneiform | 0 DLTs |
| Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Ejection Fraction Decreased | 0 DLTs |
| Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Diarrhoea | 0 DLTs |
| Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Fatigue | 0 DLTs |
| Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Anaemia | 0 DLTs |
| Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Nausea | 0 DLTs |
| Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Malaise | 0 DLTs |
| Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | General Physical Health Deterioration | 0 DLTs |
| Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | General Physical Health Deterioration | 0 DLTs |
| Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Rash | 0 DLTs |
| Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Blood Creatinine Increased | 0 DLTs |
| Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Fatigue | 0 DLTs |
| Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Nausea | 1 DLTs |
| Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Ejection Fraction Decreased | 1 DLTs |
| Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Vomiting | 1 DLTs |
| Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Diarrhoea | 0 DLTs |
| Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Dermatitis Acneiform | 0 DLTs |
| Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Anaemia | 0 DLTs |
| Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Incidence of Dose Limiting Toxicities (DLT) During the First Cycle | Malaise | 0 DLTs |
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.
Time frame: 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.
Time frame: Cycle 1 (up to 28 days)
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Best Overall Response (BOR) | Progressive disease | 1 participants |
| Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Best Overall Response (BOR) | Partial Response | 0 participants |
| Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Best Overall Response (BOR) | Complete Response | 0 participants |
| Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Best Overall Response (BOR) | Unknown | 0 participants |
| Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Best Overall Response (BOR) | Stable Disease | 5 participants |
| Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Best Overall Response (BOR) | Partial Response | 0 participants |
| Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Best Overall Response (BOR) | Progressive disease | 2 participants |
| Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Best Overall Response (BOR) | Complete Response | 0 participants |
| Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Best Overall Response (BOR) | Unknown | 0 participants |
| Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Best Overall Response (BOR) | Stable Disease | 4 participants |
| Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Best Overall Response (BOR) | Partial Response | 0 participants |
| Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Best Overall Response (BOR) | Progressive disease | 1 participants |
| Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Best Overall Response (BOR) | Unknown | 1 participants |
| Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Best Overall Response (BOR) | Stable Disease | 4 participants |
| Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Best Overall Response (BOR) | Complete Response | 0 participants |
| Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Best Overall Response (BOR) | Stable Disease | 2 participants |
| Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Best Overall Response (BOR) | Complete Response | 0 participants |
| Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Best Overall Response (BOR) | Partial Response | 0 participants |
| Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Best Overall Response (BOR) | Progressive disease | 2 participants |
| Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Best Overall Response (BOR) | Unknown | 2 participants |
| Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Best Overall Response (BOR) | Progressive disease | 3 participants |
| Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Best Overall Response (BOR) | Complete Response | 0 participants |
| Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Best Overall Response (BOR) | Unknown | 0 participants |
| Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Best Overall Response (BOR) | Partial Response | 0 participants |
| Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Best Overall Response (BOR) | Stable Disease | 3 participants |
| Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Best Overall Response (BOR) | Complete Response | 0 participants |
| Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Best Overall Response (BOR) | Progressive disease | 2 participants |
| Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Best Overall Response (BOR) | Partial Response | 0 participants |
| Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Best Overall Response (BOR) | Unknown | 1 participants |
| Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Best Overall Response (BOR) | Stable Disease | 5 participants |
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.
Time frame: Cycle 1 (up to 28 days)
Population: 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.
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.
Time frame: Cycle 1 (up to 28 days)
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Progression Free Survival (PFS) | 3.6 weeks |
| Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Progression Free Survival (PFS) | 3.4 weeks |
| Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Progression Free Survival (PFS) | 4 weeks |
| Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Progression Free Survival (PFS) | 3.7 weeks |
| Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Progression Free Survival (PFS) | 3.1 weeks |
| Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: Assessment of The Preliminary Anti-tumor Activity - Progression Free Survival (PFS) | 3.8 weeks |
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.
Time frame: From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit)
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib/II: The Number of Subjects Experiencing At Least One Adverse Event (AE) | 6 participants |
| Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib/II: The Number of Subjects Experiencing At Least One Adverse Event (AE) | 6 participants |
| Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib/II: The Number of Subjects Experiencing At Least One Adverse Event (AE) | 6 participants |
| Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib/II: The Number of Subjects Experiencing At Least One Adverse Event (AE) | 6 participants |
| Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib/II: The Number of Subjects Experiencing At Least One Adverse Event (AE) | 6 participants |
| Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib/II: The Number of Subjects Experiencing At Least One Adverse Event (AE) | 8 participants |
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: * 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)
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib/II: The Number of Subjects Experiencing At Least One Serious Adverse Event (SAE) | 3 participants |
| Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib/II: The Number of Subjects Experiencing At Least One Serious Adverse Event (SAE) | 1 participants |
| Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib/II: The Number of Subjects Experiencing At Least One Serious Adverse Event (SAE) | 3 participants |
| Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib/II: The Number of Subjects Experiencing At Least One Serious Adverse Event (SAE) | 4 participants |
| Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib/II: The Number of Subjects Experiencing At Least One Serious Adverse Event (SAE) | 2 participants |
| Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib/II: The Number of Subjects Experiencing At Least One Serious Adverse Event (SAE) | 6 participants |
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.
Time frame: Cycle 1 (Day 1)
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: PK Parameters for AEB071 - AUC0-8hr (Cycle 1; Day 1) | 7448.5 hr*ng/ml | Geometric Coefficient of Variation 46.34 |
| Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: PK Parameters for AEB071 - AUC0-8hr (Cycle 1; Day 1) | 7136 hr*ng/ml | Geometric Coefficient of Variation 25.09 |
| Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: PK Parameters for AEB071 - AUC0-8hr (Cycle 1; Day 1) | 15090 hr*ng/ml | Geometric Coefficient of Variation 53.89 |
| Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: PK Parameters for AEB071 - AUC0-8hr (Cycle 1; Day 1) | 14051.2 hr*ng/ml | Geometric Coefficient of Variation 45.83 |
| Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: PK Parameters for AEB071 - AUC0-8hr (Cycle 1; Day 1) | 18840.8 hr*ng/ml | Geometric Coefficient of Variation 36.24 |
| Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: PK Parameters for AEB071 - AUC0-8hr (Cycle 1; Day 1) | 15217.1 hr*ng/ml | Geometric Coefficient of Variation 71.48 |
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.
Time frame: Cycle 1 (Day 15)
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: PK Parameters for AEB071 - AUC0-8hr (Cycle 1; Day 15) | 5879.9 hr*ng/ml | Geometric Coefficient of Variation 32.46 |
| Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: PK Parameters for AEB071 - AUC0-8hr (Cycle 1; Day 15) | 6330.3 hr*ng/ml | Geometric Coefficient of Variation 29.28 |
| Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: PK Parameters for AEB071 - AUC0-8hr (Cycle 1; Day 15) | 16737.1 hr*ng/ml | Geometric Coefficient of Variation 17.56 |
| Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: PK Parameters for AEB071 - AUC0-8hr (Cycle 1; Day 15) | 15313.6 hr*ng/ml | Geometric Coefficient of Variation 105.21 |
| Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: PK Parameters for AEB071 - AUC0-8hr (Cycle 1; Day 15) | 15055.5 hr*ng/ml | Geometric Coefficient of Variation 78.89 |
| Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: PK Parameters for AEB071 - AUC0-8hr (Cycle 1; Day 15) | 20629.7 hr*ng/ml | Geometric Coefficient of Variation 11.81 |
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.
Time frame: Cycle 1 (Day 1)
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: PK Parameters for MEK162 - AUC0-8hr (Cycle 1; Day 1) | 1587.7 hr*ng/ml | Geometric Coefficient of Variation 55.75 |
| Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: PK Parameters for MEK162 - AUC0-8hr (Cycle 1; Day 1) | 1496.7 hr*ng/ml | Geometric Coefficient of Variation 30.02 |
| Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: PK Parameters for MEK162 - AUC0-8hr (Cycle 1; Day 1) | 1088.7 hr*ng/ml | Geometric Coefficient of Variation 49.45 |
| Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: PK Parameters for MEK162 - AUC0-8hr (Cycle 1; Day 1) | 1590.5 hr*ng/ml | Geometric Coefficient of Variation 43.49 |
| Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: PK Parameters for MEK162 - AUC0-8hr (Cycle 1; Day 1) | 984.4 hr*ng/ml | Geometric Coefficient of Variation 72.57 |
| Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: PK Parameters for MEK162 - AUC0-8hr (Cycle 1; Day 1) | 962 hr*ng/ml | Geometric Coefficient of Variation 50.15 |
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.
Time frame: Cycle 1 (Day 15)
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: PK Parameters for MEK162 - AUC0-8hr (Cycle 1; Day 15) | 1807.4 hr*ng/ml | Geometric Coefficient of Variation 43.6 |
| Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: PK Parameters for MEK162 - AUC0-8hr (Cycle 1; Day 15) | 1927.9 hr*ng/ml | Geometric Coefficient of Variation 42.48 |
| Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: PK Parameters for MEK162 - AUC0-8hr (Cycle 1; Day 15) | 1374.2 hr*ng/ml | Geometric Coefficient of Variation 68.21 |
| Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (DDS) | Phase Ib: PK Parameters for MEK162 - AUC0-8hr (Cycle 1; Day 15) | 1454.7 hr*ng/ml | Geometric Coefficient of Variation 41.13 |
| Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: PK Parameters for MEK162 - AUC0-8hr (Cycle 1; Day 15) | 1268.5 hr*ng/ml | Geometric Coefficient of Variation 70.41 |
| Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (DDS) | Phase Ib: PK Parameters for MEK162 - AUC0-8hr (Cycle 1; Day 15) | 1275.8 hr*ng/ml | Geometric Coefficient of Variation 39.04 |
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.
Time frame: From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit)
Population: 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.
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.
Time frame: From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit)
Population: 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.
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.
Time frame: From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit)
Population: 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.
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.
Time frame: From first dose of Cycle 1, Day 1 (C1D1) to time to progression (up to 18 months from Last Patient First Visit)
Population: 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.
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.
Time frame: Cycle 1 (Day 1)
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (DDS) | Phase lb: PK Parameters for AEB071 - Cmax (Cycle 1; Day 1) | 1837.5 ng/ml | Geometric Coefficient of Variation 35.9 |
| Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (DDS) | Phase lb: PK Parameters for AEB071 - Cmax (Cycle 1; Day 1) | 1932.5 ng/ml | Geometric Coefficient of Variation 31.18 |
| Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (DDS) | Phase lb: PK Parameters for AEB071 - Cmax (Cycle 1; Day 1) | 2968.1 ng/ml | Geometric Coefficient of Variation 58.32 |
| Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (DDS) | Phase lb: PK Parameters for AEB071 - Cmax (Cycle 1; Day 1) | 2813 ng/ml | Geometric Coefficient of Variation 36.83 |
| Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (DDS) | Phase lb: PK Parameters for AEB071 - Cmax (Cycle 1; Day 1) | 4459 ng/ml | Geometric Coefficient of Variation 26.45 |
| Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (DDS) | Phase lb: PK Parameters for AEB071 - Cmax (Cycle 1; Day 1) | 3768.7 ng/ml | Geometric Coefficient of Variation 57.12 |
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.
Time frame: Cycle 1 (Day 15)
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (DDS) | Phase lb: PK Parameters for AEB071 - Cmax (Cycle 1; Day 15) | 1244.6 ng/ml | Geometric Coefficient of Variation 27.5 |
| Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (DDS) | Phase lb: PK Parameters for AEB071 - Cmax (Cycle 1; Day 15) | 1347.1 ng/ml | Geometric Coefficient of Variation 28.56 |
| Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (DDS) | Phase lb: PK Parameters for AEB071 - Cmax (Cycle 1; Day 15) | 3065.6 ng/ml | Geometric Coefficient of Variation 60.1 |
| Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (DDS) | Phase lb: PK Parameters for AEB071 - Cmax (Cycle 1; Day 15) | 3263.8 ng/ml | Geometric Coefficient of Variation 96.11 |
| Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (DDS) | Phase lb: PK Parameters for AEB071 - Cmax (Cycle 1; Day 15) | 3597.2 ng/ml | Geometric Coefficient of Variation 62.84 |
| Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (DDS) | Phase lb: PK Parameters for AEB071 - Cmax (Cycle 1; Day 15) | 3716.5 ng/ml | Geometric Coefficient of Variation 23.72 |
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.
Time frame: Cycle 1 (Day 1)
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (DDS) | Phase lb: PK Parameters for AEB071 - Tmax (Cycle 1; Day 1) | 1.6 hr |
| Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (DDS) | Phase lb: PK Parameters for AEB071 - Tmax (Cycle 1; Day 1) | 1.1 hr |
| Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (DDS) | Phase lb: PK Parameters for AEB071 - Tmax (Cycle 1; Day 1) | 1.5 hr |
| Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (DDS) | Phase lb: PK Parameters for AEB071 - Tmax (Cycle 1; Day 1) | 1 hr |
| Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (DDS) | Phase lb: PK Parameters for AEB071 - Tmax (Cycle 1; Day 1) | 1 hr |
| Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (DDS) | Phase lb: PK Parameters for AEB071 - Tmax (Cycle 1; Day 1) | 2.1 hr |
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.
Time frame: Cycle 1 (Day 15)
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (DDS) | Phase lb: PK Parameters for AEB071 - Tmax (Cycle 1; Day 15) | 2 hr |
| Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (DDS) | Phase lb: PK Parameters for AEB071 - Tmax (Cycle 1; Day 15) | 1.5 hr |
| Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (DDS) | Phase lb: PK Parameters for AEB071 - Tmax (Cycle 1; Day 15) | 2.6 hr |
| Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (DDS) | Phase lb: PK Parameters for AEB071 - Tmax (Cycle 1; Day 15) | 3.9 hr |
| Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (DDS) | Phase lb: PK Parameters for AEB071 - Tmax (Cycle 1; Day 15) | 1.9 hr |
| Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (DDS) | Phase lb: PK Parameters for AEB071 - Tmax (Cycle 1; Day 15) | 2.1 hr |
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.
Time frame: Cycle 1 (Day 1)
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (DDS) | Phase lb: PK Parameters for MEK162 - Cmax (Cycle 1; Day 1) | 362 ng/ml | Geometric Coefficient of Variation 46.74 |
| Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (DDS) | Phase lb: PK Parameters for MEK162 - Cmax (Cycle 1; Day 1) | 432.6 ng/ml | Geometric Coefficient of Variation 56.3 |
| Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (DDS) | Phase lb: PK Parameters for MEK162 - Cmax (Cycle 1; Day 1) | 245.4 ng/ml | Geometric Coefficient of Variation 63.08 |
| Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (DDS) | Phase lb: PK Parameters for MEK162 - Cmax (Cycle 1; Day 1) | 328.4 ng/ml | Geometric Coefficient of Variation 59.07 |
| Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (DDS) | Phase lb: PK Parameters for MEK162 - Cmax (Cycle 1; Day 1) | 243.5 ng/ml | Geometric Coefficient of Variation 53.27 |
| Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (DDS) | Phase lb: PK Parameters for MEK162 - Cmax (Cycle 1; Day 1) | 222.8 ng/ml | Geometric Coefficient of Variation 58.13 |
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.
Time frame: Cycle 1 (Day 15)
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (DDS) | Phase lb: PK Parameters for MEK162 - Cmax (Cycle 1; Day 15) | 454.5 ng/ml | Geometric Coefficient of Variation 42.42 |
| Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (DDS) | Phase lb: PK Parameters for MEK162 - Cmax (Cycle 1; Day 15) | 418.9 ng/ml | Geometric Coefficient of Variation 34.62 |
| Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (DDS) | Phase lb: PK Parameters for MEK162 - Cmax (Cycle 1; Day 15) | 307 ng/ml | Geometric Coefficient of Variation 88.45 |
| Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (DDS) | Phase lb: PK Parameters for MEK162 - Cmax (Cycle 1; Day 15) | 362.7 ng/ml | Geometric Coefficient of Variation 59.8 |
| Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (DDS) | Phase lb: PK Parameters for MEK162 - Cmax (Cycle 1; Day 15) | 340.7 ng/ml | Geometric Coefficient of Variation 80.64 |
| Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (DDS) | Phase lb: PK Parameters for MEK162 - Cmax (Cycle 1; Day 15) | 284.1 ng/ml | Geometric Coefficient of Variation 52.79 |
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.
Time frame: Cycle 1 (Day 1)
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (DDS) | Phase lb: PK Parameters for MEK162 - Tmax (Cycle 1; Day 1) | 1.1 hr |
| Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (DDS) | Phase lb: PK Parameters for MEK162 - Tmax (Cycle 1; Day 1) | 1.1 hr |
| Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (DDS) | Phase lb: PK Parameters for MEK162 - Tmax (Cycle 1; Day 1) | 2 hr |
| Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (DDS) | Phase lb: PK Parameters for MEK162 - Tmax (Cycle 1; Day 1) | 4 hr |
| Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (DDS) | Phase lb: PK Parameters for MEK162 - Tmax (Cycle 1; Day 1) | 2 hr |
| Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (DDS) | Phase lb: PK Parameters for MEK162 - Tmax (Cycle 1; Day 1) | 1.1 hr |
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.
Time frame: Cycle 1 (Day 15)
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Phase Ib: AEB071 150 mg Bid + MEK162 45 mg Bid (DDS) | Phase lb: PK Parameters for MEK162 - Tmax (Cycle 1; Day 15) | 2 hr |
| Phase Ib: AEB071 200 mg Bid + MEK162 45 mg Bid (DDS) | Phase lb: PK Parameters for MEK162 - Tmax (Cycle 1; Day 15) | 1.6 hr |
| Phase Ib: AEB071 300 mg Bid + MEK162 30 mg Bid (DDS) | Phase lb: PK Parameters for MEK162 - Tmax (Cycle 1; Day 15) | 3 hr |
| Phase Ib: AEB071 300 mg Bid + MEK162 45 mg Bid (DDS) | Phase lb: PK Parameters for MEK162 - Tmax (Cycle 1; Day 15) | 2.9 hr |
| Phase Ib: AEB071 350 mg Bid + MEK162 30 mg Bid (DDS) | Phase lb: PK Parameters for MEK162 - Tmax (Cycle 1; Day 15) | 1.9 hr |
| Phase Ib: AEB071 400 mg Bid + MEK162 30 mg Bid (DDS) | Phase lb: PK Parameters for MEK162 - Tmax (Cycle 1; Day 15) | 1.5 hr |