| General information |
| Database: | DB00190 |
| Objective: | MEKi addition to BRAFi therapy has been reported to increase response rate (RR) and duration of response. The BRAFi ENCO (LGX818) and MEKi BINI (MEK162) have each shown promising singleagent activity in BRAFV600-mutant melanoma. |
| Authors: | Sullivan RJ, et al |
| Title: | a phase Ib/II study of BRAF inhibitor (BRAFi) encorafenib (ENCO) plus MEK inhibitor (MEKi) binimetinib (BINI) in cutaneous melanoma patients naive to BRAFi treatment. |
| Journal: | J Clin Oncol |
| Year: | 2015 |
| PMID: | http://meeting.ascopubs.org/cgi/content/abstract/33/15_suppl/9007 |
| Trial Design |
| Clinical Trial Id: | NCT01543698 |
| Agent: | encorafenib (ENCO) and binimetinib (BINI)
|
| Target: | BRAF and MEK
|
| Cancer Type: | melanoma |
| Cancer Subtype: | BRAF V600-mutant cutaneous melanoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | encorafenib (ENCO) + binimetinib (BINI) |
| Study Type: | a phase (Ph) Ib/II openlabel study |
| Key Patients Feature: | patients (pts) with BRAFV600-mutant cutaneous melanoma |
| Biomarker: | BRAF V600-mutant |
| Biomark Analysis: | NA |
| Control Group Info: | ENCO 600 mg + BINI 45 mg twice daily vs 450 mg daily + BINI 45 mg twice daily |
| Treatment Info: | Based on Ph Ib doseescalation findings, the safety and efficacy of ENCO 600 mg or 450 mg daily + BINI 45 mg twice daily are being investigated in the Ph II part of the study. |
| Primary End Point: | safety and efficacy |
| Secondary End Point: | NA |
| Patients Number: | 55 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | The confirmed RR among pts treated at ENCO 400/450 mg was 78% (1 CR + 6 PRs) and at ENCO 600 mg was 72% (3 CRs + 25 PRs). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | Ph Ib and Ph II combined (all doses) median progression free survival (95% CI) was 11.3 (7.414.6) mo, and in pts with baseline lactate dehydrogenase (LDH) > upper limit of normal (ULN; n = 21) and less than and equal to ULN (n = 32), was 6.8 (5.011.3) mo and 20.0 (11.0not reached) mo, respectively. |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | common adverse events (AEs; all grades [Grs] > 30%) were nausea (54%), diarrhea (44%), fatigue and arthralgia (33% each), and vomiting, pyrexia, and increased AST (31% each).Gr 3/4 AEs occurred in 64% of pts treated with 600 mg, commonly including increased ALT (18%), lipase (15%), AST (13%), and creatine phosphokinase (13%). |
| Conclusions: | These data suggest that ENCO + BINI is well tolerated at multiple doses, with promising activity in BRAFinaive pts with BRAFmutant melanoma. A Ph III trial (COLUMBUS) is underway using ENCO 450 mg daily with BINI. Clinical trial information NCT01543698 |