| General information |
| Database: | DB00193 |
| Objective: | No approved therapies exist that specifically target NRASmutant melanoma (¡Ö 20% of cases). In this study of BRAF V600 or NRASmutant melanoma, binimetinib, a potent and selective MEK1/2 inhibitor, was the first targeted therapy to show preliminary clinical activity in NRASadvanced melanoma. |
| Authors: | Carla van Herpen, et al |
| Title: | Overall survival and biomarker results from a phase 2 study of MEK1/2 inhibitor binimetinib (MEK162) in patients with advanced NRASmutant melanoma |
| Journal: | Annals of Oncology |
| Year: | 2014 |
| PMID: | http://annonc.oxfordjournals.org/content/25/suppl_4/mdu438.43 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | binimetinib
|
| Target: | MEK1/2
|
| Cancer Type: | melanoma |
| Cancer Subtype: | advanced/unresectable or metastatic BRAF V600 or NRASmutant melanoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a phase II openlabel single arm study |
| Key Patients Feature: | patients with advanced/unresectable or metastatic BRAF V600 or NRASmutant melanoma |
| Biomarker: | BRAF V600 or NRASmutant(CCND1 or CCND3 amplifications were exclusively seen in 5 patients with shorter PFS (less than and equal to 3.6 mos), suggesting the hypothesis that constitutive CDK4/6 pathway signaling may play a role in resistance.) |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | binimetinib 45 mg orally twice daily (bid);Updated efficacy, safety, and biomarker analyses of a larger NRASmutant subgroup than previously reported are presented here. |
| Primary End Point: | objective response rate (ORR); |
| Secondary End Point: | progression free survival (PFS) and overall survival (OS). |
| Patients Number: | 117 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | 14.5% (1 CR, 16 PRs); |
| Disease Control Rate: | disease control rate (more than and equal to SD) was 56%. |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | Median PFS was 3.6 mos (95% CI, 2.6-3.8); |
| Median OS A vs. C: | median OS was 12.2 mos (Lotheyr 95% CI, 7.9). |
| Adverse Event(agent arm): | The most common treatmentrelated adverse events (AEs) were dermatitis acneiform (54%), increased blood creatine phosphokinase (CK, 51%), and peripheral edema (42%). The most common grade 3/4 AE was increased blood CK (25%). |
| Conclusions: | Binimetinib 45mg bid is active in NRASmutant melanoma with an acceptable safety profile. A pivotalphase 3 study (NEMO) evaluating binimetinib in NRASmutant melanoma is ongoing. Understanding of the genetic landscape will be further refined from data collected in the NEMO study. |