Phase 2
N=183
A Phase II Study of Single Agent MEK162 in Patients With Advanced Melanoma
BRAF or NRAS Mutant Metastatic Melanoma
Bottom Line
View on ClinicalTrials.gov: NCT01320085 ↗Enrolled (actual)
183
Serious AEs
32.2%
Results posted
Jan 2021
Primary outcome: Primary: Percentage of Participants With Objective Response (OR) — 4.9; 14.5; 12.0 percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- MEK162 (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Pfizer
- Primary completion
- Jan 2014
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Objective Response (OR) |
4.9; 14.5; 12.0 | — |
| SECONDARY Progression-Free Survival (PFS) |
3.5; 3.6; 1.8 | — |
| SECONDARY Overall Survival (OS) |
NA; NA; 16.6 | — |
| SECONDARY Duration of Response (DOR) |
3.6; 4.0; NA | — |
| SECONDARY Time to Response (TTR) |
2.2; 1.9; 1.8 | — |
| SECONDARY Number of Participants With Grade 3 or 4 Treatment-Emergent Adverse Reactions Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.0 |
19; 52; 13 | — |
| SECONDARY Number of Participants With Serious Adverse Reactions |
2; 12; 4 | — |
| SECONDARY Number of Participants With Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 (Hematology) |
28; 63; 10; 1; 8; 1 | — |
| SECONDARY Number of Participants With Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 (Chemistries) |
14; 43; 11; 13; 41; 4 | — |
| SECONDARY Number of Participants With Shift From Baseline in Vital Signs Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 (Blood Pressure) |
4; 6; 0; 7; 14; 6 | — |
| SECONDARY Number of Participants With Markedly Abnormal Vital Sign Values: Sitting Pulse Rate |
1; 2; 1; 1; 6; 1 | — |
| SECONDARY Number of Participants With Markedly Abnormal Vital Sign Values: Weight |
6; 11; 8; 2; 8; 0 | — |
| SECONDARY Number of Participants With Notable Electrocardiogram (ECG) Values |
5; 15; 3; 1; 4; 0 | — |
| SECONDARY Number of Participants With Change From Baseline in Abnormal Ophthalmoscopy Values- by Fundoscopy |
10; 43; 13; 2; 4; 1 | — |
| SECONDARY Number of Participants With Change From Baseline in Abnormal Ophthalmoscopy Values- by Slit Lamp Examination |
4; 25; 7; 3; 8; 5 | — |
| SECONDARY Area Under the Curve From Time Zero to End of Dosing Interval at Steady-State (AUCtau) of Binimetinib |
1606.73; 1704.80; 1587.47; 2438.22; 2051.70; 2637.48 | — |
| SECONDARY Maximum Plasma Concentration (Cmax) of Binimetinib |
445.8; 471.6; 542.5; 385.2; 479.7; 531.3 | — |
| SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax) of Binimetinib |
0.68; 1.50; 0.75; 1.50; 1.48; 1.42 | — |
| SECONDARY Area Under the Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-last) of Binimetinib |
1318.38; 1447.07; 1622.66; 1806.28; 1832.06; 2263.46 | — |
| SECONDARY The Last Time Point of the Last Quantifiable Concentration (Tlast) of Binimetinib |
7.23; 7.98; 7.00; 7.50; 8.00; 7.50 | — |
| SECONDARY Trough Plasma Concentration (Ctrough) of Binimetinib |
127.0; 102.3; 136.1 | — |
| SECONDARY Apparent Total Body Clearance (CL/F) of Binimetinib |
28.01; 26.40; 37.80; 18.46; 20.50; 21.17 | — |
| SECONDARY Area Under the Curve From Time Zero to End of Dosing Interval at Steady-State (AUCtau) of Binimetinib's Metabolite |
257.73; 170.11; 248.82; 253.93; 322.21 | — |
| SECONDARY Maximum Plasma Concentration (Cmax) of Binimetinib's Metabolite |
56.37; 49.42; 56.71; 32.31; 33.55; 25.47 | — |
| SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax) of Binimetinib's Metabolite |
1.50; 1.50; 1.50; 2.50; 1.50; 1.50 | — |
| SECONDARY Area Under the Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-last) of Binimetinib's Metabolite |
197.29; 181.60; 189.37; 157.35; 129.13; 87.11 | — |
| SECONDARY The Last Time Point of the Last Quantifiable Concentration (Tlast) of Binimetinib's Metabolite |
7.23; 7.98; 7.00; 7.50; 8.00; 7.25 | — |
| SECONDARY Trough Plasma Concentration (Ctrough) of Binimetinib's Metabolite |
12.85; 11.63; 16.10 | — |
| SECONDARY Percent Change From Baseline in Histological Score (H-score) for Phosphorylated Extracellular Signal-Regulated Kinase (pERK) From Tumor Samples of Cytoplasmic and Nuclear Cellular Compartment |
-10.90; -50.11; -9.85; 195.19; -66.83; -32.35 | — |
| SECONDARY Percent Change From Baseline in Delta CT Values for Dual Specificity Phosphatase 6 (DUSP6) Expression From Tumor Samples |
-50.25; -30.82; 29.48 | — |
Summary
The study will assess the safety and efficacy of single-agent MEK162 in adult patients with locally advanced and unresectable or metastatic malignant cutaneous melanoma, harboring BRAFV600E or NRAS mutations.
Eligibility Criteria
Inclusion Criteria
- Locally advanced or metastatic cutaneous melanoma AJCC Stage IIIB to IV, not potentially curable with surgery
- BRAF or NRAS mutation in tumor tissue
- All patients enrolled should provide sufficient fresh or archival tumor sample at baseline to enable confirmation of BRAF or NRAS mutations and the additional analyses described in the protocol
- Evidence of measurable tumor disease as per RECIST
- WHO performance status of 0-2
- Adequate organ function and laboratory parameters
Exclusion Criteria
- History or evidence of central serous retinopathy (CSR), retinal vein occlusion (RVO) or any eye condition that would be considered a risk factor for CSR or RVO
- Patients with unstable CNS metastasis
- Prior treatment with a MEK- inhibitor
- Impaired cardiovascular function
- HIV, active Hepatitis B, and/or active Hepatitis C infection
- Pregnant or nursing (lactating) women
- Women of child-bearing potential UNLESS they comply with protocol contraceptive requirements
Other protocol-defined inclusion/exclusion criteria may apply.
Data sourced from ClinicalTrials.gov (NCT01320085). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.